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Objective: To investigate whether the combination of chemotherapy with staged Chinese herbal medicine (CHM) therapy could enhance health-related quality of life (QoL) in non-small-cell lung cancer (NSCLC) patients and prolong the time before deterioration of lung cancer symptoms, in comparison to chemotherapy alone. Methods: A prospective, double-blind, randomized, controlled trial was conducted from December 14, 2017 to August 28, 2020. A total of 180 patients with stage I B–IIIA NSCLC from 5 hospitals in Shanghai were randomly divided into chemotherapy combined with CHM (chemo+CHM) group (120 cases) or chemotherapy combined with placebo (chemo+placebo) group (60 cases) using stratified blocking randomization. The European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life-Core 30 Scale (QLQ-C30) was used to evaluate the patient-reported outcomes (PROs) during postoperative adjuvant chemotherapy in patients with early-stage NSCLC. Adverse events (AEs) were assessed in the safety analysis. Results: Out of the total 180 patients, 173 patients (116 in the chemo+CHM group and 57 in the chemo+placebo group) were included in the PRO analyses. The initial mean QLQ-C30 Global Health Status (GHS)/QoL scores at baseline were 57.16 ± 1.64 and 57.67 ± 2.25 for the two respective groups (P>0.05). Compared with baseline, the chemo+CHM group had an improvement in EORTC QLQ-C30 GHS/QoL score at week 18 [least squares mean (LSM) change 17.83, 95% confidence interval (CI) 14.29 to 21.38]. Conversely, the chemo+placebo group had a decrease in the score (LSM change −13.67, 95% CI −22.70 to −4.63). A significant between-group difference in the LSM GHS/QoL score was observed, amounting to 31.63 points (95% CI 25.61 to 37.64, P<0.001). The similar trends were observed in physical functioning, fatigue and appetite loss. At week 18, patients in the chemo+CHM group had a higher proportion of improvement or stabilization in GHS/QoL functional and symptom scores compared to chemo+placebo group (P<0.001). The median time to deterioration was longer in the chemo+CHM group for GHS/QoL score [hazard ratio (HR)=0.33, 95% CI 0.23 to 0.48, P<0.0010], physical functioning (HR=0.43, 95% CI 0.25 to 0.75, P=0.0005), fatigue (HR=0.47, 95% CI 0.30 to 0.72, P<0.0001) and appetite loss (HR=0.65, 95% CI 0.42 to 1.00, P=0.0215). The incidence of AEs was lower in the chemo+CHM group than in the chemo+placebo group (9.83% vs. 15.79%, P=0.52). Conclusion: The staged CHM therapy could help improve the PROs of postoperative patients with early-stage NSCLC during adjuvant chemotherapy, which is worthy of further clinical research. (Registry No. NCT03372694) [ABSTRACT FROM AUTHOR]

Background Encouraging antitumor activity of nab-paclitaxel plus S-1 (AS) has been shown in several small-scale studies. This study compared the efficacy and safety of AS versus standard-of-care nab-paclitaxel plus gemcitabine (AG) as a first-line treatment for advanced pancreatic cancer (PC). Methods In this multicenter, randomized, phase II trial, eligible patients with unresectable, locally advanced, or metastatic PC were recruited and randomly assigned (1:1) to receive AS (nab-paclitaxel 125 mg/m2 on days 1 and 8; S-1 twice daily on days 1 through 14) or AG (nab-paclitaxel 125 mg/m2 on days 1 and 8; gemcitabine 1000 mg/m2 on days 1 and 8) for 6 cycles. The primary endpoint was progression-free survival (PFS). Results Between July 16, 2019, and September 9, 2022, 62 patients (AS, n  = 32; AG, n  = 30) were treated and evaluated. With a median follow-up of 8.36 months at preplanned interim analysis (data cutoff, March 24, 2023), the median PFS (8.48 vs 4.47 months; hazard ratio [HR], 0.402; P  = .002) and overall survival (OS; 13.73 vs 9.59 months; HR, 0.226; P  < .001) in the AS group were significantly longer compared to the AG group. More patients had objective response in the AS group than AG group (37.50% vs 6.67%; P  = .005). The most common grade 3-4 adverse events were neutropenia and leucopenia in both groups, and gamma glutamyl transferase increase was observed only in the AG group. Conclusion The first-line AS regimen significantly extended both PFS and OS of Chinese patients with advanced PC when compared with the AG regimen, with a comparable safety profile. (ClinicalTrials.gov Identifier: NCT03636308). [ABSTRACT FROM AUTHOR]

Purpose: To investigate the efficacy of sequential gemcitabine and epirubicin therapy on high-risk non-muscle invasive bladder cancer (NMIBC) after transurethral resection of bladder tumour (TURBT). Methods: The records of 100 high-risk NMIBC patients, who underwent TURBT at the Tongling People's Hospital, Tongling City, China between January 2020 and March 2023 were retrospectively analyzed. A total of 46 patients, treated with epirubicin after operation, were assigned to control group, while 54 patients, treated with both gemcitabine and epirubicin, were included in the study group. DKK-1 and YKL-4 levels were assayed by immunomagnetic bead -based liquid chip technology and enzyme-linked immunosorbent assay, respectively. Furthermore, treatment efficacy was determined and compared between the two groups. Results: There were no significant differences in the pre-treatment DKK-1 and YKL-40 levels between the two groups (p > 0.05). However, both groups experienced a significant drop in post-treatment levels, with significantly lower post-treatment levels in the study group (p < 0.05). There were no significant differences in catheter retention time and hospitalization time between the two groups (p > 0.05). The study group achieved a significantly better overall response rate than the control group. The pre-treatment SF-36 scores of the two groups were similar, while their post-treatment SF-36 scores increased significantly (p < 0.05). Conclusion: Sequential therapy with gemcitabine and epirubicin is effective in the therapy of high-risk NMIBC after TURBT. It significantly lowers DKK-1 and YKL-40 levels, improves postoperative quality of life and reduces the postoperative recurrence rate without increasing adverse reactions and affecting the catheter retention and hospitalization times. A more comprehensive analysis is required to obtain improved outcomes. [ABSTRACT FROM AUTHOR]

Purpose: Long-term bladder instillation therapy will bring more infusion side effects and economic consumption to patients. This study aims to compare short-term gemcitabine vs. long-term epirubicin for intravesical chemotherapy in patients diagnosed with moderate- to high-risk NMIBC treated using transurethral resection of bladder tumor (TURBT). Materials and methods: This randomized controlled trial enrolled patients diagnosed with pT1 bladder cancer who underwent TURBT at Tianjin Medical University Cancer Institute from (01/2015- 07/2018), randomized 1:1 to gemcitabine vs. epirubicin. Recurrence-free survival (RFS) and progression-free survival (PFS) were monitored by cystoscopy. Side-effects after intravesical instillation and QLQ-C30 questionnaire were collected. Results: Finally, 208 patients were enrolled. The median follow-up was 50.6 (6–69) months. The median RFS of the gemcitabine vs. epirubicin groups were 46.7 (6–69) vs. 47.2 (8–69) months, respectively (P > 0.05); the median PFS was 51.3 (9–69) vs. 50.9 (27–69) months, respectively (P > 0.05). The incidence rates of lower urinary tract symptoms, dysuria, hypo gastralgia, and gastrointestinal symptoms in the epirubicin group were 33.3%, 6.7%, 17.7%, and 18.3%, compared with 8.5%, 3.4%, 8.5% and, 1.2%, respectively, for gemcitabine. The gemcitabine group had a better quality of life than epirubicin in global health status (82.8 ± 8.5 vs. 79.6 ± 4.2, P = 0.01) and pain symptom domain (1.1 ± 2.8 vs. 2.4 ± 3.8, P = 0.04). Conclusions: There are no significant differences in efficacy between gemcitabine and epirubicin for intravesical chemotherapy in patients with moderate to high-risk NMIBC to prevent tumor recurrence or progression for patients intolerant to BCG or those for whom BCG is not accessible. Patients with gemcitabine suffer fewer adverse events and have a better health status than with epirubicin. [ABSTRACT FROM AUTHOR]

Background: Programmed cell death protein 1 (PD-1) monoclonal antibody, pembrolizumab, is a promising drug for platinum-pretreated, recurrent or metastatic nasopharyngeal cancer (NPC). We aimed to assess the cost-effectiveness of pembrolizumab compared with chemotherapy for Chinese patients in this NPC. Methods: The cost-effectiveness of pembrolizumab versus chemotherapy was evaluated using a partitioned survival model with a 5-year boundary. Efficacy and toxicity data were derived from the KEYNOTE-122 trials. Economic indicators including life-years (LYs), quality-adjusted life-years (QALYs), incremental cost-effectiveness ratio (ICER), and lifetime cost were used. One-way analysis and probabilistic sensitivity analysis (PSA) were performed to explore the uncertainties. Additionally, various scenario analyses, including different pembrolizumab price calculations and discount rates were performed. Results: Pembrolizumab or chemotherapy alone respectively yielded 2.82 QALYs (3.96 LYs) and 2.73 QALYs (3.93 LYs) with an ICER of $422,535 per QALYs ($1,232,547 per LYs). This model was primarily influenced by the price of pembrolizumab. Furthermore, PSA indicated that pembrolizumab had none probability of being cost-effective compared with chemotherapy at a willingness-to- pay (WTP) of $38223. Scenario analyses revealed that irrespective of any potential price reduction or adjustments in the discount rate, no discernible impact on the ultimate outcome was observed. Conclusion: Pembrolizumab was less cost-effective for patients with platinum-pretreated, recurrent or metastatic NPC compared with chemotherapy in China. [ABSTRACT FROM AUTHOR]

Objective: To present the global research features and hotspots, and forecast the emerging trends by conducting a bibliometric analysis based on literature related to autophagy of pancreatic cancer from 2011 to 2022. Methods: The literature data regarding autophagy of pancreatic cancer were retrieved and downloaded from the Web of Science Core Collection (WOSCC) from Clarivate Analytics on June 10th, 2022. VOSviewer (version 1.6.18) was used to perform the bibliometric analysis. Results: A total of 616 studies written by 3993 authors, covered 45 countries and 871 organizations, published in 263 journals and co-cited 28152 references from 2719 journals. China (n=260, 42.2%) and the United States (n=211, 34.3%) were the most frequent publishers and collaborated closely. However, publications from China had a low average number of citations (25.35 times per paper). The output of University of Texas MD Anderson Cancer Center ranked the first with 26 papers (accounting for 4.2% of the total publications). Cancers (n=23, 3.7%; Impact Factor = 6.639) published most papers in this field and was very pleasure to accept related researches. Daolin Tang and Rui Kang published the most papers (n=18, respectively). The research hotspots mainly focused on the mechanisms of autophagy in tumor onset and progression, the role of autophagy in tumor apoptosis, and autophagy-related drugs in treating pancreatic cancer (especially combined therapy). The emerging topics were chemotherapy resistance mediated by autophagy, tumor microenvironment related to autophagy, autophagy-depended epithelial-mesenchymal transition (EMT), mitophagy, and the role of autophagy in tumor invasion. Conclusion: Attention has been increasing in autophagy of pancreatic cancer over the past 12 years. Our results undoubtedly provide scholars with new clues and ideas in this field. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the feasibility of using a multigene signature to tailor individualised adjuvant therapy for patients with operable triple negative breast cancer., Design: Randomised, multicentre, open label, phase 3 trial., Setting: 7 cancer centres in China between 3 January 2016 and 17 July 2023., Participants: Female patients aged 18-70 years with early triple negative breast cancer after definitive surgery., Interventions: After risk stratification using the integrated signature, patients at high risk were randomised (1:1) to receive an intensive adjuvant treatment comprising four cycles of docetaxel, epirubicin, and cyclophosphamide followed by four cycles of gemcitabine and cisplatin (arm A; n=166) or a standard treatment of four cycles of epirubicin and cyclophosphamide followed by four cycles of docetaxel (arm B; n=170). Patients at low risk received the same adjuvant chemotherapy as arm B (arm C; n=168)., Main Outcome Measures: The primary endpoint was disease-free survival in the intention-to-treat analysis for arm A versus arm B. Secondary endpoints included disease-free survival for arm C versus arm B, recurrence-free survival, overall survival, and safety., Results: Among the 504 enrolled patients, 498 received study treatment. At a median follow-up of 45.1 months, the three year disease-free survival rate was 90.9% for patients in arm A and 80.6% for patients in arm B (hazard ratio 0.51, 95% confidence interval (CI) 0.28 to 0.95; P=0.03). The three year recurrence-free survival rate was 92.6% in arm A and 83.2% in arm B (hazard ratio 0.50, 95% CI 0.25 to 0.98; P=0.04). The three year overall survival rate was 98.2% in arm A and 91.3% in arm B (hazard ratio 0.58, 95% CI 0.22 to 1.54; P=0.27). The rates of disease-free survival (three year disease-free survival 90.1% v 80.6%; hazard ratio 0.57, 95% CI 0.33 to 0.98; P=0.04), recurrence-free survival (three year recurrence-free survival 94.5% v 83.2%; 0.42, 0.22 to 0.81; P=0.007), and overall survival (three year overall survival 100% v 91.3%; 0.14, 0.03 to 0.61; P=0.002) were significantly higher in patients in arm C than in those in arm B with the same chemotherapy regimen. The incidence of grade 3-4 treatment related adverse events were 64% (105/163), 51% (86/169), and 54% (90/166) for arms A, B, and C, respectively. No treatment related deaths occurred., Conclusions: The multigene signature showed potential for tailoring adjuvant chemotherapy for patients with operable triple negative breast cancer. Intensive regimens incorporating gemcitabine and cisplatin into anthracycline/taxane based therapy significantly improved disease-free survival with manageable toxicity., Trial Registration: ClinicalTrials.gov NCT02641847., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at https://www.icmje.org/disclosure-of-interest/ and declare: support from the National Key Research and Development Project of China, National Natural Science Foundation of China, Science and Technology Commission of Shanghai Municipality, Shanghai Key Laboratory of Breast Cancer, SHDC Municipal Project for Developing Emerging and Frontier Technology in Shanghai Hospitals, and CSPC Pharmaceutical Co Ltd, Shijiazhuang, China, for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Nivolumab, recently proven in a phase 3 clinical trial (CheckMate 901) to enhance survival when combined with gemcitabine-cisplatin for advanced urothelial carcinoma. This study aimed to assess its cost-effectiveness against gemcitabine-cisplatin alone, from US and Chinese payers' perspectives., Methods: A partitioned survival model was established to assess the life-years, quality-adjusted life-years (QALYs), lifetime costs, and incremental cost-effectiveness ratios (ICERs) of nivolumab plus gemcitabine-cisplatin versus gemcitabine-cisplatin alone as first-line treatment for advanced urothelial carcinoma. Univariate, two-way, and probabilistic sensitivity analyses were conducted to assess the model's robustness. Additionally, subgroup analyses were performed., Results: Nivolumab plus gemcitabine-cisplatin and gemcitabine-cisplatin achieved survival benefits of 4.238 life-years and 2.979 life-years for patients with advanced urothelial carcinoma, respectively. Compared with gemcitabine-cisplatin, nivolumab plus gemcitabine-cisplatin resulted in ICERs of $116,856/QALY in the US and $51,997/QALY in China. The probabilities of achieving cost-effectiveness at the current willingness-to-pay thresholds were 77.5% in the US and 16.5% in China. Cost-effectiveness could be reached if the price of nivolumab were reduced to $920.87/100mg in China. Subgroup analyses indicated that the combination had the highest probability of cost-effectiveness in patients under 65 or with an Eastern Cooperative Oncology Group (ECOG) performance-status score of 0 in the US and China., Conclusion: Nivolumab plus gemcitabine-cisplatin first-line treatment for advanced urothelial carcinoma results in longer life expectancy than gemcitabine-cisplatin, but is not cost-effective in China at current price. However, cost-effectiveness is likely to be achieved in most patient subgroups in the US., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Xiang, Huang, Gan, Wang, Ding, Wu, Xing and Liu.)

Background: Pucotenlimab, also called HX008, is a humanized anti-PD-1 antagonist IgG4 mAb. It blocks programmed cell death protein 1 (PD-1), programmed-death ligand 1 (PD-L1), and programmed death ligand-2 (PDL2). In the CBCSG 006 trial, gemcitabine plus cisplatin (GP) has shown impressive antitumor activity as first-line therapy for metastatic triplenegative breast cancer (mTNBC). The phase 1b study was conducted to assess the safety and preliminary antitumor activity of pucotenlimab when combined with GP in patients with mTNBC in the first-line setting. Methods: Eligible patients with mTNBC with =6 months of DFI (disease-free interval) who have never received antitumor therapy for metastatic disease were screened. Participants received pucotenlimab at 3 mg/kg (d1, q3w) plus gemcitabine at 1,250 mg/m² (d1, 8, q3w) and cisplatin at 75 mg/m² (d1, q3w). Eligible patients received up to six cycles of pucotenlimab along with GP chemotherapy, while pucotenlimab could be maintained until disease progression or unacceptable toxicity occurred or withdrawal of informed consent. This study was registered in China under registration number CTR20191353. Results: Between July 2019 and March 2020, 31 patients were enrolled in this study. The median age was 50 (range 28-68) years. Among 31 patients who were evaluated, 25 (80.6%) experienced objective response and the other six (19.4%) experienced stable disease (SD). As of 4 August, the median progression-free survival (PFS) was 9.0 months (95% CI, 6.2-9.2). The most common grade 3 or 4 treatment-related adverse events included neutropenia (74.1%), anemia (35.5%), thrombocytopenia (32.3%), hypocalcemia (9.7%), hypokalemia (9.7%), and alanine aminotransferase increased (6.5%). There were no treatment-related deaths. Conclusion: Pucotenlimab plus GP demonstrated promising activity and a manageable safety profile in patients with mTNBC in the first-line setting. [ABSTRACT FROM AUTHOR]

Background: Empirical chemotherapy remains the standard of care in patients with unfavourable cancer of unknown primary (CUP). Gene-expression profiling assays have been developed to identify the tissue of origin in patients with CUP; however, their clinical benefit has not yet been demonstrated. We aimed to evaluate the efficacy and safety of site-specific therapy directed by a 90-gene expression assay compared with empirical chemotherapy in patients with CUP., Methods: This randomised controlled trial was conducted at Fudan University Shanghai Cancer Center (Shanghai, China). We enrolled patients aged 18-75 years, with previously untreated CUP (histologically confirmed metastatic adenocarcinoma, squamous cell carcinoma, poorly differentiated carcinoma, or poorly differentiated neoplasms) and an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, who were not amenable to local radical treatment. Patients were randomly assigned (1:1) by the Pocock and Simon minimisation method to receive either site-specific therapy or empirical chemotherapy (taxane [175 mg/m 2 by intravenous infusion on day 1] plus platinum [cisplatin 75 mg/m 2 or carboplatin area under the curve 5 by intravenous infusion on day 1], or gemcitabine [1000 mg/m 2 by intravenous infusion on days 1 and 8] plus platinum [same as above]). The minimisation factors were ECOG performance status and the extent of the disease. Clinicians and patients were not masked to interventions. The tumour origin in the site-specific therapy group was predicted by the 90-gene expression assay and treatments were administered accordingly. The primary endpoint was progression-free survival in the intention-to-treat population. The trial has been completed and the analysis is final. This study is registered with ClinicalTrials.gov (NCT03278600)., Findings: Between Sept 18, 2017, and March 18, 2021, 182 patients (105 [58%] male, 77 [42%] female) were randomly assigned to receive site-specific therapy (n=91) or empirical chemotherapy (n=91). The five most commonly predicted tissues of origin in the site-specific therapy group were gastro-oesophagus (14 [15%]), lung (12 [13%]), ovary (11 [12%]), cervix (11 [12%]), and breast (nine [10%]). At the data cutoff date (April 30, 2023), median follow-up was 33·3 months (IQR 30·4-51·0) for the site-specific therapy group and 30·9 months (27·6-35·5) for the empirical chemotherapy group. Median progression-free survival was significantly longer with site-specific therapy than with empirical chemotherapy (9·6 months [95% CI 8·4-11·9] vs 6·6 months [5·5-7·9]; unadjusted hazard ratio 0·68 [95% CI 0·49-0·93]; p=0·017). Among the 167 patients who started planned treatment, 46 (56%) of 82 patients in the site-specific therapy group and 52 (61%) of 85 patients in the empirical chemotherapy group had grade 3 or worse treatment-related adverse events; the most frequent of these in the site-specific therapy and empirical chemotherapy groups were decreased neutrophil count (36 [44%] vs 42 [49%]), decreased white blood cell count (17 [21%] vs 26 [31%]), and anaemia (ten [12%] vs nine [11%]). Treatment-related serious adverse events were reported in five (6%) patients in the site-specific therapy group and two (2%) in the empirical chemotherapy group. No treatment-related deaths were observed., Interpretation: This single-centre randomised trial showed that site-specific therapy guided by the 90-gene expression assay could improve progression-free survival compared with empirical chemotherapy among patients with previously untreated CUP. Site-specific prediction by the 90-gene expression assay might provide more disease information and expand the therapeutic armamentarium in these patients., Funding: Clinical Research Plan of Shanghai Hospital Development Center, Program for Shanghai Outstanding Academic Leader, and Shanghai Anticancer Association SOAR PROJECT., Translation: For the Chinese translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests QX and YS are employees of Canhelp Genomics, Hangzhou, China. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: In the treatment of advanced pancreatic cancer, chemotherapy plays a pivotal role. Despite its effectiveness, this regimen is often marred by side effects such as anemia, neuropathy, fatigue, nausea, and malnutrition, which significantly affect patients' tolerance to the treatment. Some studies have shown that vitamin C could potentially augment chemotherapy's tolerability, notably by boosting iron absorption, ameliorating anemia, and relieving pain and numbness in hands and feet. Nevertheless, the integration of vitamin C with chemotherapy to mitigate toxic side effects and enhance the quality of life for advanced pancreatic cancer patients has not been examined in any randomized controlled trials to date., Methods: A prospective, single-center, open-label, randomized controlled trial will be conducted at Fudan University Shanghai Cancer Center from September 2023 to September 2026. A total of at least 100 patients with advanced pancreatic adenocarcinoma exhibiting distant metastases will be recruited and randomly assigned to the chemotherapy group or the chemotherapy plus vitamin C group. The primary endpoint is the rate of anemia. Secondary endpoints include the rate of grade 3 neuropathy, change of numeric rating scale, quality of life, and overall survival., Discussion: This study aims to assess the impact of low-dose vitamin C on enhancing the quality of life for patients with metastatic pancreatic cancer undergoing gemcitabine and nab-paclitaxel chemotherapy., Trial Registration: The trial was registered with the ClinicalTrials.gov (NCT06018883) on August 31, 2023., (© 2024. The Author(s).)

Introduction: Patients with pancreatic ductal adenocarcinoma (PDAC) remain a poor prognosis despite the development of chemotherapy. Although programmed cell death 1 (PD-1) blockade has shown great efficacy in various solid tumours, its application in treating PDAC is limited. Recent studies have indicated that chemotherapy or stereotactic body radiotherapy (SBRT) may improve the antitumour effect of PD-1 blockade in patients with PDAC. The objective of this study is to evaluate the efficacy and safety of combined therapy comprising PD-1 blockade, gemcitabine plus nab-paclitaxel chemotherapy and SBRT for patients with metastatic PDAC., Methods and Analysis: This is a multicentre, single-arm, prospective phase II clinical trial. Forty-three patients diagnosed with metastatic PDAC will be enrolled. The eligible patients will be intravenously administered 1000 mg/m 2 gemcitabine and 125 mg/m 2 nab-paclitaxel on days 1 and 8 of the 21-day cycle. Serplulimab (200 mg) will be administered intravenously on day 1 of the 21-day cycle. Furthermore, during the second cycle, the patients will undergo SBRT with doses of 33 Gy in five fractions for primary lesions or doses of 24 Gy in three fractions for metastases. The primary endpoint is the 6-month progression-free survival (PFS) rate. The secondary endpoints overall survival, PFS, overall response rate, disease control rate, time to progression, duration of response, duration of disease control and safety. Moreover, this trial seeks to investigate biomarkers such as circulating tumour DNA and circulating hybrid cells in patients diagnosed with metastatic PDAC., Ethics and Dissemination: The study was approved by the Ethics Committee on Biomedical Research, West China Hospital of Sichuan University. The study results will be presented at international conferences and published in a peer-reviewed journal., Trial Registration Number: ChiCTR2300073237., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Anti-PD-1 therapy and chemotherapy is a recommended first-line treatment for recurrent or metastatic nasopharyngeal carcinoma, but the role of PD-1 blockade remains unknown in patients with locoregionally advanced nasopharyngeal carcinoma. We assessed the addition of sintilimab, a PD-1 inhibitor, to standard chemoradiotherapy in this patient population., Methods: This multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial was conducted at nine hospitals in China. Adults aged 18-65 years with newly diagnosed high-risk non-metastatic stage III-IVa locoregionally advanced nasopharyngeal carcinoma (excluding T3-4N0 and T3N1) were eligible. Patients were randomly assigned (1:1) using blocks of four to receive gemcitabine and cisplatin induction chemotherapy followed by concurrent cisplatin radiotherapy (standard therapy group) or standard therapy with 200 mg sintilimab intravenously once every 3 weeks for 12 cycles (comprising three induction, three concurrent, and six adjuvant cycles to radiotherapy; sintilimab group). The primary endpoint was event-free survival from randomisation to disease recurrence (locoregional or distant) or death from any cause in the intention-to-treat population. Secondary endpoints included adverse events. This trial is registered with ClinicalTrials.gov (NCT03700476) and is now completed; follow-up is ongoing., Findings: Between Dec 21, 2018, and March 31, 2020, 425 patients were enrolled and randomly assigned to the sintilimab (n=210) or standard therapy groups (n=215). At median follow-up of 41·9 months (IQR 38·0-44·8; 389 alive at primary data cutoff [Feb 28, 2023] and 366 [94%] had at least 36 months of follow-up), event-free survival was higher in the sintilimab group compared with the standard therapy group (36-month rates 86% [95% CI 81-90] vs 76% [70-81]; stratified hazard ratio 0·59 [0·38-0·92]; p=0·019). Grade 3-4 adverse events occurred in 155 (74%) in the sintilimab group versus 140 (65%) in the standard therapy group, with the most common being stomatitis (68 [33%] vs 64 [30%]), leukopenia (54 [26%] vs 48 [22%]), and neutropenia (50 [24%] vs 46 [21%]). Two (1%) patients died in the sintilimab group (both considered to be immune-related) and one (<1%) in the standard therapy group. Grade 3-4 immune-related adverse events occurred in 20 (10%) patients in the sintilimab group., Interpretation: Addition of sintilimab to chemoradiotherapy improved event-free survival, albeit with higher but manageable adverse events. Longer follow-up is necessary to determine whether this regimen can be considered as the standard of care for patients with high-risk locoregionally advanced nasopharyngeal carcinoma., Funding: National Natural Science Foundation of China, Key-Area Research and Development Program of Guangdong Province, Natural Science Foundation of Guangdong Province, Overseas Expertise Introduction Project for Discipline Innovation, Guangzhou Municipal Health Commission, and Cancer Innovative Research Program of Sun Yat-sen University Cancer Center., Translation: For the Chinese translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Objective: To compare the effectiveness and safety of nab-paclitaxel, cisplatin, and capecitabine (nab-TPC) with gemcitabine and cisplatin as an alternative first line treatment option for recurrent or metastatic nasopharyngeal carcinoma., Design: Phase 3, open label, multicentre, randomised trial., Setting: Four hospitals located in China between September 2019 and August 2022., Participants: Adults (≥18 years) with recurrent or metastatic nasopharyngeal carcinoma., Interventions: Patients were randomised in a 1:1 ratio to treatment with either nab-paclitaxel (200 g/m 2 on day 1), cisplatin (60 mg/m 2 on day 1), and capecitabine (1000 mg/m 2 twice on days 1-14) or gemcitabine (1 g/m 2 on days 1 and 8) and cisplatin (80 mg/m 2 on day 1)., Main Outcome Measures: Progression-free survival was evaluated by the independent review committee as the primary endpoint in the intention-to-treat population., Results: The median follow-up was 15.8 months in the prespecified interim analysis (31 October 2022). As assessed by the independent review committee, the median progression-free survival was 11.3 (95% confidence interval 9.7 to 12.9) months in the nab-TPC cohort compared with 7.7 (6.5 to 9.0) months in the gemcitabine and cisplatin cohort. The hazard ratio was 0.43 (95% confidence interval 0.25 to 0.73; P=0.002). The objective response rate in the nab-TPC cohort was 83% (34/41) versus 63% (25/40) in the gemcitabine and cisplatin cohort (P=0.05), and the duration of response was 10.8 months in the nab-TPC cohort compared with 6.9 months in the gemcitabine and cisplatin cohort (P=0.009). Treatment related grade 3 or 4 adverse events, including leukopenia (4/41 (10%) v 13/40 (33%); P=0.02), neutropenia (6/41 (15%) v 16/40 (40%); P=0.01), and anaemia (1/41 (2%) v 8/40 (20%); P=0.01), were higher in the gemcitabine and cisplatin cohort than in the nab-TPC cohort. No deaths related to treatment occurred in either treatment group. Survival and long term toxicity are still being evaluated with longer follow-up., Conclusion: The nab-TPC regimen showed a superior antitumoural efficacy and favourable safety profile compared with gemcitabine and cisplatin for recurrent or metastatic nasopharyngeal carcinoma. Nab-TPC should be considered the standard first line treatment for recurrent or metastatic nasopharyngeal carcinoma. Longer follow-up is needed to confirm the benefits for overall survival., Trial Registration: Chinese Clinical Trial Registry ChiCTR1900027112., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from the Guangdong Basic and Applied Basic Research Foundation, National Natural Science Foundation of China, CPSF, and Postdoctoral Fellowship Program of CPSF for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Addition of gemcitabine and cisplatin (GP) or docetaxel and cisplatin plus fluorouracil (TPF) to concurrent chemoradiotherapy (CCRT) significantly improved survival in locoregionally advanced nasopharyngeal carcinoma (NPC). However, an economic evaluation of these regimens remains unknown. The purpose of this study is to compare the cost-effectiveness of GP versus TPF regimen in the treatment of locoregionally advanced NPC in China. Materials and methods: A comprehensive Markov model was developed to evaluate the health and economic outcomes of GP versus TPF regimen for patients with locoregionally advanced NPC. Baseline and clinical outcome were derived from 158 patients with newly diagnosed stage III-IVA NPC between 2010 and 2015. We evaluated the quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs) from the perspective of the Chinese healthcare system. One-way sensitive analysis explored the impact of uncertainty in key model parameters on results, and probabilistic uncertainty was assessed through a Monte Carlo probabilistic sensitivity analysis. Results: GP regimen provided an additional 0.42 QALYs with incremental cost of $3,821.99, resulting in an ICER of $9,099.98 per QALY versus TPF regimen at the real-world setting. One-way sensitivity analysis found that the results were most sensitive to the cost and proportion of receiving subsequent treatment in two groups. The probability that GP regimen being cost-effective compared with TPF regimen was 86.9% at a willingness-to-pay (WTP) of $31,008.16 per QALY. Conclusion: Using real-world data, GP regimen was demonstrated a cost-effective alternative to TFP regimen for patients with locoregionally advanced NPC in China. It provides valuable evidence for clinicians when making treatment decisions to improve the cost-effectiveness of treatment. [ABSTRACT FROM AUTHOR]

Purpose: Although several trials have confirmed the treatment efficacy of induction chemotherapy followed by concurrent chemoradiotherapy (CCRT) in locoregionally advanced nasopharyngeal carcinoma (NPC) from endemic area of China, little is known about the best regime for induction chemotherapy in non-endemic region. This study compared the treatment effect of Gemcitabine and cisplatin (GP) versus docetaxel and cisplatin (TP) followed by concurrent chemoradiotherapy in locoregionally advanced NPC from non-endemic area of China. Materials and methods: A total of 196 locoregionally advanced NPC patients were enrolled in this study, with 142 and 54 patients in TP and GP followed by concurrent chemoradiotherapy groups. The primary endpoint was treatment response of induction chemotherapy. The secondary endpoints included disease-free survival. The Kaplan–Meier method was used to evaluate the efficacy between treatment groups. Results: The median follow-up time was 45.5 months (range: 6–60.5 months). During induction chemotherapy course, GP contributed higher treatment response rate than TP (68.1% vs. 47.1%, p = 0.007). Patients in GP group had better DFS and LRFS than those in TP group (3-year and 5-year DFS, 86.8% and 82.5% vs. 71.7% and 68%, p = 0.036; 3-year and 5-year LRFS, 96.2% and 96.2% vs. 90.5% and 82.8%, p = 0.03). No significant difference of adverse events was observed between two treatment groups in the whole course. Conclusion: This study suggested that GP followed by CCRT was better than TP followed by CCRT in improving survival outcomes of locoregionally advanced NPC patients from non-endemic area of China. [ABSTRACT FROM AUTHOR]

Purpose: A randomized phase III trial demonstrated that gemcitabine plus cisplatin (GP) prolonged progression-free survival and overall survival compared with fluorouracil plus cisplatin (FP) as first-line chemotherapy in patients with metastatic nasopharyngeal carcinoma (NPC). The cost-effectiveness analysis was designed to identify the economic option for metastatic NPC from a Chinese societal perspective. Methods: We established a Markov model that involved three health states representing the stages of disease to simulate therapy. Survival data of clinical outcomes were derived from the trial and adjusted to quality-adjusted life years (QALYs). Transition probabilities and health utilities were obtained from the clinical trial and published literatures. The cost-effective strategy was estimated for these treatments using a willing-to-pay (WTP) threshold. A one-way sensitivity analysis was conducted to study the influences of parameters. Results: GP treatment group produced a gain of 0.37 QALYs with an incremental cost of $2520.80, yielding an incremental cost-effectiveness ratio (ICER) of $6812.97 per QALY, compared with FP treatment ($15,530.96 versus $13,010.16). The ICER was lower than the accepted WTP threshold, which was 3 times gross domestic product per capita of China ($25,749 per QALY). Conclusion: GP regimen is more cost-effective compared with FP regimen as the first-line treatment for Chinese patients with metastatic NPC. [ABSTRACT FROM AUTHOR]

Background: Peripheral T-cell lymphoma (PTCL) is often prone to relapse and progression even after formal first-line treatment, and there is no standard regimen for second-line treatment. What is more, the activity of thalidomide against this type of lymphoma is unknown. Purpose: The objective of this study was to evaluate the efficacy and safety of GDPT regimen in the treatment of relapsed/refractory peripheral T-cell lymphoma. Patients and methods: In this retrospective study, gemcitabine, cisplatin, prednisone, and thalidomide (GDPT) combination regimen was used as salvage protocol for PTCL that failed in first-line treatment for 29 patients and it was scheduled to give 6 cycles of GDPT therapy in order to better evaluate the efficacy unless there was evidence of disease progression, unacceptable toxicities, or refusal by the patient. Results: After a total of 106 cycles of GDPT regimen were administered, the result showed that the disease control rate (DCR) achieved 82.8% and overall response rate (ORR) reached 69.0% with 34.5% complete remission (CR) and 34.5% partial remission (PR). The median progression-free survival (PFS) was 10.0 months (95% CI 6.6–13.4) and median OS was 28.0 months (95% CI 19.2–36.8). And the 1-year PFS rate and 1-year OS rate were 43.6% and 64.6%, respectively. Both hematologic and non-hematologic toxicities were moderate and well tolerated. There was no treatment-related death. Conclusion: Thalidomide in combination with gemcitabine, cisplatin, prednisone regimen is a new promising approach to treating patients with relapse and refractory PTCL. [ABSTRACT FROM AUTHOR]

Purpose: Compared with conventional fluorouracil plus cisplatin (FP) regimen, gemcitabine plus cisplatin (GP) can prolong survival in patients with recurrent or metastatic nasopharyngeal carcinoma, but the economic impact of this practice remains unknown. It's significant to evaluate its values by taking both efficacy and cost into consideration.Methods: We developed a Markov model with 10 years horizon to compare the cost-effectiveness of GP and FP regimen. Clinical data came from a multicentre, randomised, open-label, phase 3 trial. Direct costs related to the treatment were estimated from the perspective of the Chinese healthcare system. Utility values were gathered from published study. Sensitivity analysis was conducted to confirm the robustness of the model.Results: The total cost of FP regimen was $12,587 and yielded 0.964 QALYs, while the total cost of GP regimen was $17,920 and yielded 1.685 QALYs. The ICER of GP regimen versus FP regimen was $7,386 which was far less than the willingness-to-pay threshold ($26,508) in China.Conclusion: From the perspective of Chinese healthcare system, GP regimen with superior efficacy was proved to be more cost-effective than the traditional FP regimen. It is likely that GP regimen may be recommended as the primarily first-line treatment option for recurrent or metastatic nasopharyngeal carcinoma. [ABSTRACT FROM AUTHOR]

Purpose: Bladder cancer (BC) ranks first in the incidence of urogenital tumors in China and second only to prostate cancer in the West. This study will clarify the roles and mechanism of lncRNA GHET1 in chemotherapeutic resistance of BC to Gemcitabine.Methods: The expression of GHET1 was examined using real-time quantitative PCR. Cell Counting Kit-8 assay was applied to analyze cell proliferation and Gemcitabine sensitivity. Cell apoptosis was detected using Annexin V-FITC/PI double-stained flow cytometry. The expression of ABCC1 protein was examined using Western blotting.Results: Firstly, the expression of GHET1 was up-regulated in BC, its high expression was relevant to high grade and muscle invasion of BC patients. Secondly, high expression of GHET1 was related to low Gemcitabine sensitivity of BC patients, and GHET1 was highly expressed in Gemcitabine-resistant BC cell lines. Thirdly, knockdown of GHET1 decreased the IC50 of Gemcitabine in Gemcitabine-resistant BC cell lines and advanced the Gemcitabine-induced cytotoxicity; GHET1 promoted Gemcitabine resistance in BC. Finally, knockdown of GHET1 also inhibited the expression of ABCC1 protein in Gemcitabine-resistant BC cells.Conclusions: High expression of GHET1 was related with the low sensitivity to Gemcitabine of BC; GHET1 contributed to chemotherapeutic resistance to Gemcitabine in BC through up-regulating ABCC1 expression. Our findings are helpful to expound the molecular mechanism of chemotherapeutic resistance in BC. [ABSTRACT FROM AUTHOR]

Background: The effectiveness of gemcitabine plus capecitabine compared with gemcitabine monotherapy for resected pancreatic cancer has been evaluated in the ESPAC-4 trial. We aimed to assess the cost-effectiveness of these adjuvant regimens on resected pancreatic cancer. Methods: A Markov model was established to simulate the disease process of resected pancreatic cancer (relapse-free survival, progressive disease, and death). The efficacy and toxicity profiles were collected from the ESPAC-4 trial. Transition probabilities were calculated based on survival in each group. Cost data were calculated from the perspective of the Chinese healthcare payer. The primary endpoint in the analysis was the incremental cost-effectiveness ratio (ICER), and model uncertainties were explored by one-way sensitivity analysis and probabilistic sensitivity analysis. Results: Our results demonstrated that gemcitabine monotherapy cost $36,028.45 and yielded a survival of 1.02 quality-adjusted life year (QALY), while gemcitabine plus capecitabine cost $46,095.05 and yielded a survival of 1.23 QALY. Therefore, the incremental cost-effectiveness ratio of gemcitabine plus capecitabine vs gemcitabine monotherapy was $45,191.23 which surpassed the willingness-to-pay threshold of $29,291.42 per QALY in China. Conclusion: The gemcitabine monotherapy regimen is more cost-effective compared with gemcitabine plus capecitabine regimen for the patients with postoperative pancreatic cancer from the Chinese societal perspective. [ABSTRACT FROM AUTHOR]

Background: Patients with N2-3 nasopharyngeal carcinoma have a high risk of treatment being unsuccessful despite the current practice of using a concurrent adjuvant cisplatin-fluorouracil regimen. We aimed to compare the efficacy and safety of concurrent adjuvant cisplatin-gemcitabine with cisplatin-fluorouracil in N2-3 nasopharyngeal carcinoma., Methods: We conducted an open-label, randomised, controlled, phase 3 trial at four cancer centres in China. Eligible patients were aged 18-65 years with untreated, non-keratinising, stage T1-4 N2-3 M0 nasopharyngeal carcinoma, an Eastern Cooperative Oncology Group performance status score of 0-1, and adequate bone marrow, liver, and renal function. Eligible patients were randomly assigned (1:1) to receive concurrent cisplatin (100 mg/m 2 intravenously) on days 1, 22, and 43 of intensity-modulated radiotherapy followed by either gemcitabine (1 g/m 2 intravenously on days 1 and 8) and cisplatin (80 mg/m 2 intravenously for 4 h on day 1) once every 3 weeks or fluorouracil (4 g/m 2 in continuous intravenous infusion for 96 h) and cisplatin (80 mg/m 2 intravenously for 4 h on day 1) once every 4 weeks, for three cycles. Randomisation was done using a computer-generated random number code with a block size of six, stratified by treatment centre and nodal category. The primary endpoint was 3-year progression-free survival in the intention-to-treat population (ie, all patients randomly assigned to treatment). Safety was assessed in all participants who received at least one dose of chemoradiotherapy. This study was registered at ClinicalTrials.gov, NCT03321539, and patients are currently under follow-up., Findings: From Oct 30, 2017, to July 9, 2020, 240 patients (median age 44 years [IQR 36-52]; 175 [73%] male and 65 [27%] female) were randomly assigned to the cisplatin-fluorouracil group (n=120) or cisplatin-gemcitabine group (n=120). As of data cutoff (Dec 25, 2022), median follow-up was 40 months (IQR 32-48). 3-year progression-free survival was 83·9% (95% CI 75·9-89·4; 19 disease progressions and 11 deaths) in the cisplatin-gemcitabine group and 71·5% (62·5-78·7; 34 disease progressions and seven deaths) in the cisplatin-fluorouracil group (stratified hazard ratio 0·54 [95% CI 0·32-0·93]; log rank p=0·023). The most common grade 3 or worse adverse events that occurred during treatment were leukopenia (61 [52%] of 117 in the cisplatin-gemcitabine group vs 34 [29%] of 116 in the cisplatin-fluorouracil group; p=0·00039), neutropenia (37 [32%] vs 19 [16%]; p=0·010), and mucositis (27 [23%] vs 32 [28%]; p=0·43). The most common grade 3 or worse late adverse event (occurring from 3 months after completion of radiotherapy) was auditory or hearing loss (six [5%] vs ten [9%]). One (1%) patient in the cisplatin-gemcitabine group died due to treatment-related complications (septic shock caused by neutropenic infection). No patients in the cisplatin-fluorouracil group had treatment-related deaths., Interpretation: Our findings suggest that concurrent adjuvant cisplatin-gemcitabine could be used as an adjuvant therapy in the treatment of patients with N2-3 nasopharyngeal carcinoma, although long-term follow-up is required to confirm the optimal therapeutic ratio., Funding: National Key Research and Development Program of China, National Natural Science Foundation of China, Guangdong Major Project of Basic and Applied Basic Research, Sci-Tech Project Foundation of Guangzhou City, Sun Yat-sen University Clinical Research 5010 Program, Innovative Research Team of High-level Local Universities in Shanghai, Natural Science Foundation of Guangdong Province for Distinguished Young Scholar, Natural Science Foundation of Guangdong Province, Postdoctoral Innovative Talent Support Program, Pearl River S&T Nova Program of Guangzhou, Planned Science and Technology Project of Guangdong Province, Key Youth Teacher Cultivating Program of Sun Yat-sen University, the Rural Science and Technology Commissioner Program of Guangdong Province, and Fundamental Research Funds for the Central Universities., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Purpose: Targeted therapy has brought great clinical benefits for patients with multiple solid tumors, but its effects in patients with locally advanced/ metastatic pancreatic cancer (LA/MPC) are disputed. This systematic evaluation compared the efficacy and safety profiles of gemcitabine combined with targeted agents (GEM + TA) versus gemcitabine administered as monotherapy or combined with placebo (GEM ± PLC) in LA/MPC patients. Methods: PubMed and EMBASE were searched for relevant randomized controlled trials published on or before April 30, 2013. The primary end points were overall survival (OS) and progression-free survival (PFS); the secondary end points were 1-year survival rate, objective response rate (ORR), and toxicity rates (TRs), defined as the prevalence of grade 3/4 adverse events. The systematic evaluation was performed by using Review Manager version 5.1.7. Findings: A total of 10 randomized controlled trials involving 3899 patients (2195 males; mean age, 63.6 years) were included in the systematic evaluation. The results reported that there was no significant difference in OS (hazard ratio [HR] = 0.97 [P = 0.85]), PFS (HR = 0.95 [P = 0.14]), or ORR (odds ratio [OR] = 0.95 [P = 0.69]) between GEM + TA and GEM ± PLC. However, a marginal difference in 1-year survival rate (OR = 0.80 [P = 0.05]) between the 2 groups was observed. The grade 3/4 TRs of anemia, diarrhea, nausea, neutropenia, thrombocytopenia, and vomiting were not significantly different between the 2 groups. However, the prevalence of grade 3/4 rash was significantly greater in the GEM + TA group (OR = 8.31 [P < 0.01]). Implications: Based on the results from this analysis, the addition of targeted agents to a regimen of gemcitabine treatment does not bring survival benefits except 1-year survival rate to patients with LA/MPC. [ABSTRACT FROM AUTHOR]

Background: There is paucity of investigations into immunotherapy or targeted therapy for postoperative locally recurrent pancreatic cancer. We aimed to assess the efficacy of stereotactic body radiotherapy (SBRT) plus pembrolizumab and trametinib in these patients., Methods: In this open-label, randomised, controlled, phase 2 study, participants were recruited from Changhai Hospital affiliated to the Naval Medical University, Shanghai, China. Eligible patients were aged 18 years or older with histologically confirmed pancreatic ductal adenocarcinoma characterised by mutant KRAS and positive immunohistochemical staining of PD-L1, Eastern Cooperative Oncology Group performance status of 0 or 1, and documented local recurrence after surgery followed by chemotherapy (mFOLFIRINOX [ie, 5-fluorouracil, oxaliplatin, irinotecan, and folinic acid] or 5-fluorouracil). Eligible participants were randomly assigned (1:1) using an interactive voice or web response system, without stratification, to receive SBRT with doses ranging from 35-40 Gy in five fractions, intravenous pembrolizumab 200 mg once every 3 weeks, and oral trametinib 2 mg once daily or SBRT (same regimen) and intravenous gemcitabine (1000 mg/m 2 ) on day 1 and 8 of a 21-day cycle for eight cycles until disease progression, death, unacceptable toxicity, or consent withdrawal. The primary endpoint was overall survival in the intention-to-treat population. Safety was assessed in the as-treated population in all participants who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, NCT02704156, and is now complete., Findings: Between Oct 10, 2016, and Oct 28, 2017, 198 patients were screened, of whom 170 patients were enrolled and randomly assigned to receive SBRT plus pembrolizumab and trametinib (n=85) or SBRT plus gemcitabine (n=85). As of the clinical cutoff date (Nov 30, 2020), median follow-up was 13·1 months (IQR 10·2-17·1). Median overall survival was 14·9 months (12·7-17·1) with SBRT plus pembrolizumab and trametinib and 12·8 months (95% CI 11·2-14·4) with SBRT plus gemcitabine (hazard ratio [HR] 0·69 [95% CI 0·51-0·95]; p=0·021). The most common grade 3 or 4 adverse effects were increased alanine aminotransferase or aspartate aminotransferase (ten [12%] of 85 in SBRT plus pembrolizumab and trametinib group vs six [7%] of 85 in SBRT plus gemcitabine group), increased blood bilirubin (four [5%] vs none), neutropenia (one [1%] vs nine [11%]), and thrombocytopenia (one [1%] vs four [5%]). Serious adverse events were reported by 19 (22%) participants in the SBRT plus pembrolizumab and trametinib group and 12 (14%) in the SBRT plus gemcitabine group. No treatment-related deaths occurred., Interpretation: The combination of SBRT plus pembrolizumab and trametinib could be a novel treatment option for patients with locally recurrent pancreatic cancer after surgery. Phase 3 trials are needed to confirm our findings., Funding: Shanghai Shenkang Center and Changhai Hospital., Translation: For the Chinese translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: There is paucity of investigations into immunotherapy or targeted therapy for postoperative locally recurrent pancreatic cancer. We aimed to assess the efficacy of stereotactic body radiotherapy (SBRT) plus pembrolizumab and trametinib in these patients., Methods: In this open-label, randomised, controlled, phase 2 study, participants were recruited from Changhai Hospital affiliated to Naval Medical University, Shanghai, China. Eligible patients were aged 18 years or older with histologically confirmed pancreatic ductal adenocarcinoma characterised by mutant KRAS and positive immunohistochemical staining of PD-L1, Eastern Cooperative Oncology Group performance status of 0 or 1, and documented local recurrence after surgery followed by chemotherapy (mFOLFIRINOX or 5-fluorouracil). Eligible participants were randomly assigned (1:1) using an interactive voice or web response system, without stratification, to receive SBRT with doses ranging from 35-40 Gy in five fractions, intravenous pembrolizumab 200 mg once every 3 weeks, and oral trametinib 2 mg once daily or SBRT (same regimen) and intravenous gemcitabine (1000 mg/m 2 ) on day 1 and 8 of a 21-day cycle for eight cycles until disease progression, death, unacceptable toxicity, or consent withdrawal. The primary endpoint was overall survival in the intention-to-treat population. Safety was assessed in the as-treated population in all participants who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, NCT02704156, and is now complete., Findings: Between Oct 10, 2016, and Oct 28, 2017, 198 patients were screen, of whom 170 patients were enrolled and randomly assigned to receive SBRT plus pembrolizumab and trametinib (n=85) or SBRT plus gemcitabine (n=85). As of the clinical cutoff date (Nov 30, 2020), median follow-up was 23·3 months (IQR 20·5-27·4). Median overall survival was 24·9 months (23·3-26·5) with SBRT plus pembrolizumab and trametinib and 22·4 months (95% CI 21·2-23·6) with SBRT plus gemcitabine (hazard ratio [HR] 0·60 [95% CI 0·44-0·82]; p=0·0012). The most common grade 3 or 4 adverse effects were increased alanine aminotransferase or aspartate aminotransferase (ten [12%] of 85 in SBRT plus pembrolizumab and trametinib group vs six [7%] of 85 in SBRT plus gemcitabine group), increased blood bilirubin (four [5%] vs none), neutropenia (one [1%] vs nine [11%]), and thrombocytopenia (one [1%] vs four [5%]). Serious adverse events were reported by 19 (22%) participants in the SBRT plus pembrolizumab and trametinib group and 12 (14%) in the SBRT plus gemcitabine group. No treatment-related deaths occurred., Interpretation: The combination of SBRT plus pembrolizumab and trametinib could be a novel treatment option for patients with locally recurrent pancreatic cancer after surgery. Phase 3 trials are needed to confirm our findings., Funding: Shanghai Shenkang Center and Changhai Hospital., Translation: For the Chinese translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: Nab-paclitaxel (Abraxane®) plus gemcitabine (AG) and Fluorouracil, leucovorin, irinotecan, oxaliplatin (FOLFIRINOX) have shown significant clinical benefit and been widely used as 1 st -line treatment of metastatic pancreatic cancer (mPC) in China. This study aims to compare the cost-effectiveness of AG versus FOLFIRINOX regimen for the treatment of mPC patients in China., Methods: Markov model was developed with a lifetime survival projection in Microsoft Excel® to simulate the progression of the mPC over time. The quality-adjusted life years (QALYs), resource consumption in the health care sector and incremental cost-effectiveness ratios (ICERs) were reported. Uncertainty was assessed by one-way and probabilistic sensitivity analyses., Results: AG regimen provided an effectiveness of 1.35 QALY at an average cost of USD 22,300 whereas FOLFIRINOX regimen brought 0.82 QALY at a cost of USD 22,980 in lifetime horizon. Therefore, AG regimen was dominant with an ICER of USD -1300 compared with FOLFIRINOX regimen. AG arm generated less drug cost, medical cost, hospitalization cost, and end-of-life cost than FOLFIRINOX arm did. Sensitivity analyses confirmed the robustness of base case findings., Conclusions: AG is likely a cost-effective option for the 1 st -line mPC treatment compared with FOLFIRINOX in China from the perspective of healthcare system.

Mono-chemotherapy with gemcitabine (difluorodeoxycytidine) is an effective cancer chemotherapy, and is often used instead of a more effective but more toxic combination chemotherapy regimen. Infection associated with gemcitabine is very rare. We present a case of Cryptococcus neoformans pneumonia that developed after 5 courses of gemcitabine for advanced bladder carcinoma. Lung biopsy and antigens demonstrated C. neoformans. The pneumonia resolved after antifungal therapy. [ABSTRACT FROM AUTHOR]

Background: Recently, patients who received induction chemotherapy plus concurrent chemoradiotherapy for locoregionally advanced nasopharyngeal carcinoma were found to have survival advantages compared with those receiving concurrent chemoradiotherapy alone in two large randomized trials. Based on these two trials, we present a cost-effectiveness analysis to compare gemcitabine and cisplatin (GP) versus cisplatin, fluorouracil, and docetaxel (TPF) for induction chemotherapy to treat locoregionally advanced nasopharyngeal carcinoma.Methods: We constructed a Markov model to compare the cost and effectiveness of GP versus TPF. Clinical data including the frequency of adverse events, recurrence and death obtained from two randomized phase III trials were used to calculate transition probabilities and costs. Health utilities were estimated from the literature. Incremental cost-effectiveness ratios, expressed as dollars per quality-adjusted life-year (QALY), were calculated, and incremental cost-effectiveness ratios less than $27,534.25/QALY (3 × the per capita GDP of China, 2018) were considered cost-effective. One-way sensitivity and probabilistic sensitivity analyses explored the robustness of the model.Results: Our base case model found that the total cost was $53,082.68 in the GP group and $45,482.66 in the TPF group. The QALYs were 6.82 and 4.11, respectively. The incremental cost-effectiveness ratio favoured the GP regimen, at an incremental cost of $2,804.44 per QALY. The probabilistic sensitivity analysis found that treatment with the GP regimen was cost-effective 100% of the time at a willingness-to-pay threshold of $27,534.25‬/QALY.Conclusion: In this model, GP was estimated to be cost-effective compared with cisplatin, fluorouracil, and docetaxel for patients with locoregionally advanced nasopharyngeal carcinoma from the payer's perspectives in the China. [ABSTRACT FROM AUTHOR]

CDA 435C>T is reported as a functional SNP but there is no relevant research on the efficacy/hematological toxicity of gemcitabine-platinum treatment in Chinese non-small-cell lung cancer (NSCLC) patients. In this study, 63 patients who received radical resection (stage IB or IIIA) and 100 advanced NSCLC (stage IIIB or IV) patients have been collected, and all were treated with gemcitabine-platinum regimens from February of 2017 to February 2019. CDA 435C>T polymorphisms have been detected by PCR and direct sequencing. CT scan results and blood routine examinations have been collected to evaluate the efficacy and hematological toxicity. Then the relationships have been analyzed about CDA 435C>T. We found that T allele carriers have better therapy response (p<0.05). Patients carrying CDA 435C/T or T/T genotypes are statistically associated with a better efficacy (p<0.05) but are more prone to leukopenia (p<0.05). Although there is no difference in grade III-IV hematologic toxicity of 163 patients (p>0.05), in the case of 100 stage IIIB-IV patients, the CDA 435C/T and T/T have an increased risk (p<0.05). Regarding the CDA 435C>T polymorphism in the Chinese population, in patients with the mutant T allele, gemcitabine is more effective, but they are more prone to suffering from hematological toxicity, especially the late-stage patients.

Objectives: To assess the efficacy and toxicity of gemcitabine-based induction chemotherapy followed by concurrent chemoradiotherapy (CCRT) in locally advanced nasopharyngeal carcinoma (LA-NPC)., Methods: Both observational studies (OBS) and randomized controlled trials (RCT) were included in the meta-analysis. Systematic online searches were conducted in Web of Sciences, PubMed, Embase, meeting proceedings and ClinicalTrials.gov from the inception to May 25, 2020. The primary endpoint of interest was overall survival., Results: five OBSs and 2 RCTs including 1680 patients were incorporated in the analysis. The evidence from the RCTs showed that adding gemcitabine-based induction chemotherapy to CCRT significantly improved progression free survival (hazard ratio (HR): 0.60, 95% confidence interval (CI): 0.40-0.88; P = .010; chi square P = .25; I2 = 24%) and overall survival (HR: 0.47; 95% CI: 0.28-0.80; P = 0.005; chi square P = .49, I2 = 0%) and was related to a higher risk of hematological toxicities. Furthermore, based on the data of OBSs, overall survival (HR: 0.52; 95% CI: 0.31-0.88; P = .02; chi square P = .37, I2 = 6%) was significantly improved in patients treated with gemcitabine-based induction chemotherapy compared to those treated with taxane-based induction chemotherapy. However, the progression free survival (HR: 0.67; 95% CI: 0.45-1.01; P = .06; chi square P = .74; I2 = 0%) showed no significant difference., Conclusions: For LA-NPC patients, adding gemcitabine-based induction chemotherapy to CCRT significantly improved overall survival and progression free survival with a higher risk of hematological toxicities when compared to CCRT alone. Also, gemcitabine-based regimen could be used as an alternative induction chemotherapy regimen to taxane-based regimen in the treatment of LA-NPC., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: There have not been any head-to-head prospective studies to compare the effects of different chemotherapy regimens as first-line treatments for unresectable pancreatic cancer (UPC). We aimed to compare the effectiveness of nab-paclitaxel plus gemcitabine, mFOLFIRINOX and gemcitabine plus oxaliplatin (GEMOX) as first-line treatments by using real-world data from Chinese patients., Methods: We retrospectively included patients with UPC treated with nab-paclitaxel plus gemcitabine, mFOLFIRINOX or GEMOX as a first-line treatment at Sun Yat-sen University Cancer Center. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR) were assessed., Results: A total of 117 patients were administered nab-paclitaxel plus gemcitabine ( n = 62), mFOLFIRINOX ( n = 30) or GEMOX ( n = 25) as first-line chemotherapy. The median OS was 11.1, 10.1 and 10.2 months ( p = 0.75) in the nab-paclitaxel plus gemcitabine, mFOLFIRINOX and GEMOX, respectively. The ORR was similar among the three groups (24%, 23% and 32%, p = 0.76) and the DCR was higher in the nab-paclitaxel-gemcitabine group (82%) than the other two groups (60% and 64%, p = 0.04). The most common adverse events of grade 3 or 4 were neutropenia (32%, 28% and 5%), peripheral neuropathy (13%, 16% and 0) and fatigue (9%, 16% and 5%). Febrile neutropenia occurred in 2%, 4% and 5% of the patients in the three groups., Conclusion: In the first line treatment of UPC, our results suggest that nab-paclitaxel plus gemcitabine was associated with a higher DCR than mFOLFIRINOX or GEMOX, while all groups demonstrated similar OS, PFS and ORR.

Platinum-based chemotherapy (PBC) has proven benefits in phase III studies for advanced triple-negative breast cancer (TNBC) patients; however, real-world data of large samples from multiple centers are lacking. Our study was to compare the effectiveness of PBC and non-PBC in advanced TNBC patients in multicenter real-world settings. Totally, 495 patients with advanced TNBC receiving PBC (n = 350) or non-PBC (n = 145) at four cancer centers in China between 2003 and 2019 were included. Treatment responses and outcomes were compared between the two groups from first-line to third-line treatment. Of patients with PBC, 249 (71.1%) received PBC from first-line chemotherapy, 86 (24.6%) from second-line and 15 (4.3%) from third-line treatment. In first-line treatment, PBC was superior to non-PBC in objective response rate (ORR, 53.0% vs 32.1%, P < .001) and median progression-free survival (PFS, 8.4 vs 6.0 months, P = .022), whereas overall survival (OS) was similar (19.2 vs 16.8 months, P = .439). When comparing patients receiving non-PBC doublets (n = 221) with those receiving PBC doublets (n = 249), the same trend was observed in ORR (32.6% vs 53.0%, P < .001), median first-line PFS (6.5 vs 8.4 months, P = .041) and median first-line OS(17.8 vs 19.2 months, P = .568). Paclitaxel/docetaxel + platinum was more likely to be used, followed by gemcitabine + platinum. In second/third-line treatment, PBC yielded a similar response and survival compared to non-PBC. Adding PBC in the first-line therapy was better than that in the latter-line of treatment in terms of ORR, PFS and OS (P < .001). Toxic effects of PBC were tolerable and the most common adverse event was neutropenia (38.6%). PBC doublets exhibited superior efficacy and manageable toxicity compared to non-PBC doublets in the first-line treatment for Chinese mTNBC patients., (© 2020 UICC.)

BACKGROUND Pancreatic cancer (PC) is a common digestive system tumor. For patients with advanced pancreatic cancer (APC), chemotherapy is still the predominant treatment. However, no large-scale clinical studies have been done of it as first-line therapy for APC. The goal of the present study was to assess real-world outcomes with chemotherapy in that setting. MATERIAL AND METHODS We retrospectively analyzed data from 322 patients with APC who were treated with chemotherapy at 4 hospitals in different cities in China. The first-line regimens used were AS (nab-paclitaxel and S-1), AG (nab-paclitaxel and gemcitabine), and FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin). RESULTS Of the patients, 232 received AS, 79 received AG, and 11 received FOLFIRINOX. The median number of chemotherapy cycles was 5. The median overall survival (mOS) was 9 months and the median progression-free survival (mPFS) was 5 months. The AS, AG, and FOLFIRINOX regimens were associated with mOS rates of 9 months, 9 months, and 10 months, respectively. The mPFS rates for the AS, AG, and FOLFIRINOX regimens were 5, 4, and 5 months, respectively. The differences between the PFS rates for the regimens were statistically significant. The overall response rate (ORR) and overall disease control rate (DCR) for chemotherapy were 38% and 81.8%, respectively. The ORRs for the AS, AG, and FOLFIRINOX regimens were 46.9%, 18.7%, and 0%, respectively. The DCRs for the AS, AG and FOLFIRINOX regimens were 87.2%, 69.3%, and 63.6%, respectively. The differences between the ORRs and DCRs for the regimens were statistically significant. The incidences of grade 3/4 adverse events (AEs) associated with the AS, AG, and FOLFIRINOX regimens were 29.9%, 25%, and 36.4%, respectively. CONCLUSIONS The AS regimen was associated with a higher ORR and DCR than the other 2 regimens, with a lower rate of AEs.

Introduction: This study aimed to evaluate the cost-effectiveness of cisplatin plus gemcitabine vs. paclitaxel plus gemcitabine as a first-line treatment for metastatic triple-negative breast cancer in China., Methods: The Markov model and partitioned survival (PS) model were used, and the study included three health states over the period of a lifetime. Transition probabilities and safety data were derived from the CBCSG006 trial (cisplatin plus gemcitabine vs. paclitaxel plus gemcitabine in patients who had acquired metastatic triple-negative breast cancer). Cost and utility values were derived from previous studies, the Chinese Drug Bidding Database, and healthcare documents. Sensitivity analyses were performed to observe model stability., Results: In the Markov model, compared with paclitaxel plus gemcitabine, cisplatin plus gemcitabine yielded an additional 0.15 QALYs, with an incremental cost of 1976.33 USD. The incremental cost-utility ratio (ICUR) was 12,826.98 USD/QALY (quality-adjusted life year). In the PS model, cisplatin plus gemcitabine yielded an additional 0.17 QALYs with an incremental cost of 2384.63 USD; the incremental cost-utility ratio (ICUR) was 13,867.7 USD/QALY. In the first scenario analysis, in which the 3-year time horizon was used in both arms, the total QALYs in the cisplatin plus gemcitabine group were larger and the costs were lower, indicating that cisplatin plus gemcitabine was superior to paclitaxel plus gemcitabine. In the second scenario, in which the progression-free (PF) utility (during chemotherapy) was 0.76, the PF utility was 0.96, and the post-progression (PP) utility was 0.55, the result obtained with the Markov model showed that the ICUR was 11,063.68 USD/QALY. In the probabilistic sensitivity analysis (PSA) on the Markov model, the probabilities that cisplatin plus gemcitabine would be cost-effective were 48.94-78.72% if the willingness-to-pay threshold was 9776.8 to 29,330.4 USD/QALY., Conclusions: The findings of the present analysis suggest that cisplatin plus gemcitabine might be much more cost-effective than paclitaxel plus gemcitabine in patients receiving first-line treatment for metastatic triple-negative breast cancer in China.

Background: Cytidine deaminase (CDA) polymorphisms may affect the response to gemcitabine/cisplatin chemotherapy in patients with non-small cell lung cancer (NSCLC). This study is designed to investigate the associations of CDA-79A>C and 208G>A polymorphisms and gemcitabine/cisplatin chemotherapy effectiveness in Xinjiang Uyghur and Han patients., Methods: This prospective cohort study enrolled consecutive patients with stage IIIb/IV NSCLC administered gemcitabine/cisplatin chemotherapy at the First Affiliated Hospital, Medical College of Shihezi University and the First People's Hospital, Kashgar Region. CDA-A79C and CDA-G208A polymorphisms were detected by direct sequencing. Progression-free survival was analyzed by the Kaplan-Meier method. Associations of A79C and G208A polymorphisms with treatment effectiveness and progression-free survival were analyzed using logistic regression and multivariate Cox regression analyses. Subgroup analyses based on ethnicity were performed., Results: The study enrolled 120 patients. A79C and G208A polymorphisms followed the Hardy-Weinberg equilibrium. The frequencies of the AA, AC, and CC genotypes and the A and C alleles of A79C were 52.2%, 29.9%, 17.9%, 67.2%, and 32.8%, respectively, in Han patients and 75.4%, 18.9%, 5.7%, 84.9%, and 5.1%, respectively, in Uyghur patients. Uyghur patients had lower frequencies of A79C-AC/CC genotypes, A79C-C allele, G208A-GA genotype, and G208A-A allele ( P <0.05). Compared with A79C-AA, the odds of ineffective chemotherapy were increased for A79C-AC (odds ratio [OR] 2.818; 95% confidence interval [95% CI] 1.031, 7.705; P =0.043) and A79C-CC (OR 9.864; 95% CI 1.232, 78.966; P =0.031). G208A polymorphisms did not influence chemotherapy effectiveness. Chemotherapy was more effective in Han patients than in Uyghur patients for A79C-AC and G208A-GG. Progression-free survival was longer for A79C-AA versus A79C-AC/CC (10 vs. 7 months, P =0.004) and G208A-GA/AA vs. G208A-AA (12 vs. 8 months, P =0.010). Polymorphisms of A79C (hazard ratio [HR] 1.617; 95% CI 1.009, 2.592; P =0.046) and G208A (HR 2.193; 95% CI 1.055, 4.557; P =0.035) were associated with progression-free survival., Conclusion: For Uyghur and Han ethnic groups, A79C and G208A polymorphisms can be used as a promising biomarker for the chemotherapy efficacy and prognosis of NSCLC.

Purpose: To assess the cost-effectiveness of osimertinib used as a second-line treatment after failure of epidermal growth factor receptor tyrosine kinase inhibitor therapy for advanced non-small cell lung cancer (NSCLC) in China., Methods: From the perspective of China's health care system, a Markov model was used for estimating the costs and health outcomes of osimertinib and 4 platinum-based chemotherapies, including pemetrexed + platinum (PP), gemcitabine + platinum (GP), docetaxel + platinum (DP), and paclitaxel + platinum (TP). Two scenarios were considered, one in all confirmed patients with T790M-positive disease (scenario 1) and the other in all patients whose disease progressed after epidermal growth factor receptor tyrosine kinase inhibitor therapy, which consisted of patients with T790M-positive or T790M-negative NSCLC (scenario 2). Clinical data for transition probabilities and treatment effects were obtained from published clinical trials. Health care resource utilization and costs were derived from local administrative databases and published literature. Deterministic and probabilistic sensitivity analyses were conducted to assess the uncertainty of the results., Findings: In the base-case analysis, compared with the 4 platinum-based chemotherapies, osimertinib yielded an additional 0.671 to 0.846 quality-adjusted life-year (QALY), with incremental costs of 15,943 to 20,299 USD in scenario 1, and an additional 0.376 to 0.808 QALY with incremental costs of 9710 to 15,407 USD in scenario 2. In the probabilistic sensitivity analysis, the probabilities that osimertinib would be cost-effective were 57.7% in scenario 1 and 58.4% in scenario 2 if the willingness-to-pay threshold were 30,000 USD/QALY, and probabilities would be more than 75 % in both scenarios if the willingness-to-pay threshold were 50,000 USD/QALY., Implications: Osimertinib is likely to be cost-effective when used as a second-line treatment of advanced NSCLC in China based on the latest reimbursement price of osimertinib through National Reimbursement Drug List negotiation., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Ovarian cancer is the third leading cause of death among gynecological cancers in women in China. Chemotherapy is an important method for comprehensive treatment of ovarian cancer, but the curative effect is poor., Purpose: In this study, gemcitabine (GEM) -loaded RGD modified liposomes (LPs) were developed by the emulsification-solvent evaporation method and evaluated for their antitumor activity in vitro and in vivo., Methods: The physicochemical properties of LPs such as particle size, zeta potential and in vitro drug release were investigated. We also demonstrated the effect of RGD-GEM-PEG LPs in ovarian cancer., Results: RGD-PEG3500-DSPE GEM LPs had a uniform spherical morphology. The mean particle size and polydispersity index were determined to be 106.7 nm and 0.13 respectively. The ER% and DL% of the formulation were 79.6±3.1% and 6.1±1.4% respectively. Compared with the free drug, RGD modified GEM LPs had sustained-release properties in vitro. In vivo, compared with the DiD-RGD-PEG3500-DSPE GEM LPs group, free DiD-GEM and DiD-GEM LPs had no obvious fluorescence intensity in tumor of mice at all times, indicating that ordinary liposomes and drugs had no tumor targeting function. RGD-PEG3500-DSPE GEM LPs showed a superior antiproliferative effect on SKOV3 cells and had a better antitumor effect in vivo than non-modified LPs., Conclusion: These results indicated that RGD-PEG3500-DSPE GEM LPs were a promising candidate for antitumor drug delivery., Competing Interests: The authors report no conflicts of interest in this work., (© 2019 Tang et al.)

Objectives: Sequential combination of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) and chemotherapy has shown greater benefits than either treatment alone in non-small-cell lung cancer (NSCLC). In this follow-up of the ENSURE study, we evaluated progression-free survival (PFS) with first-line erlotinib followed by chemotherapy at progression versus the inverse treatment sequence in 175 Chinese patients with EGFR mutation-positive NSCLC., Materials and Methods: Forty-five of the 175 patients included in the follow-up analysis experienced progressive disease (PD). Those with PD on first-line erlotinib (n = 24) received gemcitabine/cisplatin while those who failed first-line chemotherapy (n = 21) received erlotinib until second-line PD. The primary endpoint was PFS in the crossover subpopulation. Post-hoc analysis of survival outcomes was also measured for the overall population of 175 Chinese patients., Results: Among patients who crossed over at progression, PFS was comparable between those who received second-line erlotinib and those who received second-line chemotherapy (median, 26.3 months and 23.4 months, respectively; P = 0.529). Regardless of the sequence in which the therapies were administered, patients in the crossover treatment subgroup benefited from either second-line therapy after progression with a median overall survival of 51.6 months versus 23.0 months achieved among patients in the non-crossover treatment subgroup. Post-hoc biomarker analyses of Kaplan-Meier survival curves and Cox regression showed that survival benefits with either treatment sequence were similar between patients with circulating free DNA EGFR mutations in exons 19 and 21; however, those with undetectable mutations achieved significantly greater survival benefits., Conclusion: In advanced EGFR mutation-positive NSCLC, first-line erlotinib followed by chemotherapy at progression demonstrated comparable PFS benefit with the inverse treatment sequence, irrespective of mutation subtype. Utilizing both EGFR-TKIs and chemotherapy, irrespective of the sequence, maximizes survival benefits for patients., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Peripheral T cell lymphomas (PTCL) are less responsive to anthracycline-containing regimen such as CHOP and carry a poor prognosis. In this prospective study, we investigated gemcitabine, cisplatin, and dexamethasone (GDP) combined with methotrexate (MTX) and pegaspargase (PEG-L) as front-line treatment in PTCL. Eligible newly diagnosed PTCL patients received 4 cycles of the GDP-ML chemotherapy every 28 days. After 4 cycles, responding patients continued to receive either autologous stem cell transplantation or the MTX/cytarabine (MA) regimen for consolidation. This trial is registered with www.chictr.org.cn (ChiCTR-ONC-12002055). A total of 65 patients were enrolled with a median follow-up of 38.5 months. The overall response rate (ORR) was 55.4%, and complete remission rate (CR) was 33.8%. The median overall survival (OS) was 16 months, and the 1-year and 2-year OS were 59.1% and 38.2%, respectively. The median PFS was only 8 months. The main adverse event was hematologic toxicity: 50% patients showed grade III/IV neutropenia. GDP-ML for the first-line treatment of PTCL patients is an effective induction regimen compared with standard CHOP, and the toxicity was more significant but acceptable. However, future studies exploring new drug combinations are warranted to overcome relapse after remission. ClinicalTrials.gov Identifier: NCT02987244.

BACKGROUND Gemcitabine plus cisplatin (GP) is a novel regimen of induction chemotherapy (IC) for treating locoregional advanced nasopharyngeal cancer (NPC). This retrospective study aimed to compare the efficacy of GP and TP (paclitaxel plus cisplatin) regimens in tumor volume reduction after IC. MATERIAL AND METHODS Between January 2014 and July 2017, 44 patients with III-IVB stage NPC received GP IC followed by concurrent chemoradiotherapy. These patients were matched with 44 patients receiving TP IC according to clinical characteristics. The gross tumor volume of the primary site and positive lymph nodes were delineated by magnetic resonance imaging before and after IC, as well as the nasopharyngeal air cavities. The changes in tumor volume and nasopharyngeal air cavity after IC were calculated and compared between the 2 groups. Treatment toxicities and early survival outcomes were also reported. RESULTS There were no differences in the initial tumor volume and nasopharyngeal cavity between the 2 groups. The volume changes after IC for the primary site, lymph nodes, and nasopharyngeal cavity were 31.4 (range, -0.97-75.8), 4.68 (range, -7.08-22.06), and 2.62 (range, 0.1-7.63) mL for GP and 23.36 (range, -59.14-83.58), 4.7 (range, -11.21-48.61), and 1.47 (range, -2.47-6.17) mL for TP, respectively. All comparisons favored the GP regimen. The toxicities of the 2 regimens were comparable and no survival differences were observed at follow-up (median, 18.7 months). CONCLUSIONS Changes in the tumor volume and nasopharyngeal air cavity showed that the GP regimen was significantly more effective than the TP regimen in tumor burden reduction. However, whether the advantages of GP can translate into survival benefits requires further investigation.

Background: Platinum-based doublet chemotherapy regimens, preferentially gemcitabine plus cisplatin, are generally considered the first-line standard of care for patients with recurrent or metastatic nasopharyngeal carcinoma. However, no consensus has been reached regarding treatment following progression after first-line therapy. Camrelizumab (SHR-1210) is a humanised anti-programmed death-1 (anti PD-1) antibody. We present safety and preliminary antitumour activity of camrelizumab alone as second-line therapy in patients with recurrent or metastatic nasopharyngeal carcinoma and combined with gemcitabine and cisplatin as first-line therapy in this patient population., Methods: We report the results from two single-arm, phase 1 trials. Both trials included patients aged 18-70 years with histologically or cytologically confirmed nasopharyngeal carcinoma and confirmed metastatic disease or locoreginal recurrence, and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients who received at least one previous line of treatment were enrolled at five academic hospitals in China into the dose-escalation and expansion trial to receive camrelizumab monotherapy intravenously at escalating doses of 1 mg/kg, 3 mg/kg, and 10 mg/kg, and a bridging dose of 200 mg per dose once every 2 weeks (monotherapy trial). Treatment-naive patients were enrolled from a single centre in China to receive six cycles of camrelizumab 200 mg (day 1), gemcitabine 1 g/m 2 (days 1 and 8), and cisplatin 80 mg/m 2 (day 1) every 3 weeks followed by camrelizumab 200 mg maintenance once every 3 weeks (combination trial). The primary endpoint of both trials was the safety and tolerability of the study treatment. Analyses were done per protocol. Both trials are registered with ClinicalTrials.gov, number NCT02721589 (camrelizumab monotherapy trial) and NCT03121716 (camrelizumab combination trial). Both trials are ongoing, but are no longer enrolling patients., Findings: In the camrelizumab monotherapy trial, between March 31, 2016, and Sept 20, 2017, 121 patients were assessed for eligibility, of whom 93 patients were enrolled across the dose-escalation and expansion cohorts and received at least one dose of camrelizumab (safety population). 15 (16%) of 93 patients had treatment-related adverse events of grade 3 or 4, the most common of which were elevated conjugated bilirubin concentration (three [3%] of 93 patients), stomatitis, anaemia, and increased concentrations of aspartate aminotransferase, alanine aminotransferase, and total bilirubin, each of which occurred in two (2%) patients. Eight (9%) patients had a treatment-related serious adverse event. No dose-limiting toxic effects were observed during the dose-escalation phase. 31 (34%; 95% CI 24-44) of 91 evaluable patients on camrelizumab monotherapy had an overall response with a median follow-up of 9·9 months (IQR 8·1-11·7). In the camrelizumab combination trial, between April 18, 2017, and Aug 15, 2017, 24 patients were assessed for eligibility, of whom 23 patients were enrolled and treated (safety population). 20 (87%) of 23 patients had grade 3 or 4 treatment-related adverse events: neutropenia (13 [57%] of 23 patients), anaemia (11 [48%] patients), leucopenia (11 [48%] patients), thrombocytopenia (seven [30%] patients), oedema (two [9%] patients), hyponatraemia (two [9%] patients), hypochloraemia (one [4%] patients), and rash (one [4%] patient). Two patients had treatment-related serious adverse events. No treatment-related deaths occurred in these trials. 20 (91% [95% CI 72-97]) of 22 evaluable patients had an overall response with a median follow-up time of 10·2 months (IQR 9·7-10·8)., Interpretation: Camrelizumab is a well tolerated, potential treatment option for patients with recurrent or metastatic nasopharyngeal carcinoma. The combination of camrelizumab plus gemcitabine and cisplatin has a manageable toxicity profile and promising preliminary antitumour activity for this disease in treatment-naive patients. Randomised controlled trials are needed to further establish the role of immune checkpoint inhibition for nasopharyngeal carcinomas., Funding: Hengrui Medicine Co, Chinese National Natural Science Foundation project, Science and Technology Program of Guangdong, Pearl River Nova Program of Guangzhou., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Collecting duct carcinoma (CDC) is a rare type of renal cancer with a poor prognosis. As there are no standard guidelines for the management of metastatic CDC (mCDC), we evaluated the efficacy and safety of combined therapies of sorafenib, gemcitabine, plus cisplatin in patients with mCDC., Materials and Methods: A prospective, multicentre, single-arm, open-label, phase 2 trial (ClinicalTrials.gov identifier NCT01762150) that enrolled 26 mCDC patients with no prior systemic chemotherapy. Patients were treated with sorafenib (400 mg orally, twice daily) combined with chemotherapy (gemcitabine 1000 mg/m 2 , intravenously for 30-60 min on days 1 and 8, plus cisplatin 25 mg/m 2 , intravenously on days 1-3, repeated every 28 days for 4 cycles), until disease progression, unacceptable toxicity, or study discontinuation for any other reason. The primary end-points were progression-free survival (PFS) and 6-month PFS rate., Results: The 6-month PFS rate was 65%, and the median PFS was 8.8 months (95% confidence interval [CI]: 6.7-10.9) with a median overall survival of about 12.5 months (95% CI: 9.6-15.4). The objective response rate was 30.8%, and the disease control rate was 84.6%. The treatment was generally well tolerated. Major grade 3/4 toxicities included leucopenia (26.9%), thrombocytopenia (23.1%), anaemia (11.5%) and palmar-plantar erythrodysesthesia (7.7%)., Conclusions: Though the combination of sorafenib and chemotherapy demonstrated a similar outcome as that of the previously reported regimens in patients with mCDC, this combination may be a suitable option for patients who have low Eastern Cooperative Oncology Group performance status or less metastatic sites., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Purpose: To investigate the effects of intra-arterial chemotherapy on T1 stage bladder cancer (Bca) and evaluate patient outcome with bladder-preserving treatment approaches., Materials and Methods: A total of 238 patients with T1 stage Bca were retrospectively analyzed. Among them, 35 patients were categorized into the subgroup of highest-risk T1 stage according to the European Association of Urology guidelines and received immediate radical cystectomy (RC group), whereas 62 were classified as being highest-risk T1 patients but were unwilling to undergo RC and were treated with gemcitabine plus cisplatin intra-arterial chemotherapy (GC group). There were 141 T1 patients who had bladder-preserving surgery with intravesical chemotherapy (IVC group)., Results: For patients with T1 stage Bca, the GC group had a higher estimated recurrence-free survival rate (44.4 vs. 13.9%, P = 0.087), progression-free survival rate (75.4 vs. 32.8%, P = 0.006), and cancer-specific survival (CSS) rate (78.7 vs. 67.5%, P = 0.399) when compared with the IVC group, respectively. Using the multivariable regression model, the GC intra-arterial chemotherapy was significantly related to bladder preservation (P = 0.004), lower recurrence (P = 0.012), and less progression (P = 0.004). For patients with the highest-risk T1 stage, GC group did not have a poorer CSS rate in comparison with the RC group (P = 0.383). Moreover, immediate RC did not confer a survival benefit in terms of CSS when compared with those who underwent deferred RC after failing GC intra-arterial chemotherapy (P = 0.283)., Conclusions: Gemcitabine plus cisplatin intra-arterial chemotherapy may be an effective bladder-preserving alternative adjuvant treatment for patients with T1 stage Bca with oncologic benefits, good compliance, and low toxicity.

Background: Outcomes are poor for patients with recurrent or metastatic nasopharyngeal carcinoma and no well established first-line chemotherapy is available for the disease. We compared the efficacy and safety of gemcitabine plus cisplatin versus fluorouracil plus cisplatin in patients with recurrent or metastatic nasopharyngeal carcinoma., Methods: In this multicentre, randomised, open-label, phase 3 trial, patients with recurrent or metastatic nasopharyngeal carcinoma were recruited from 22 hospitals in China. Key inclusion criteria were Eastern Cooperative Oncology Group performance status of 0 or 1, adequate organ function, and measurable lesions according to Response Evaluation Criteria in Solid Tumors version 1.1. Patients were randomly assigned in a 1:1 ratio to receive either gemcitabine (1 g/m 2 intravenously on days 1 and 8) and cisplatin (80 mg/m 2 intravenously on day 1), or fluorouracil (4 g/m 2 in continuous intravenous infusion over 96 h) and cisplatin (80 mg/m 2 on day 1 given intravenously) once every 3 weeks for a maximum of six cycles. The randomisation was done centrally via an interactive phone response system using block randomisation with a size of six. The primary endpoint was progression-free survival assessed by the independent image committee in the intention-to-treat population. Safety analyses were done in patients who received at least one cycle of study drug. This study is ongoing and is registered with ClinicalTrials.gov, number NCT01528618., Findings: Between Feb 20, 2012, and Oct 30, 2015, 362 patients were randomly assigned to a group (181 to the gemcitabine [plus cisplatin] group and 181 to the fluorouracil [plus cisplatin] group). Median follow-up time for progression-free survival was 19·4 months (IQR 12·1-35·6). The median progression-free survival was 7·0 months (4·4-10·9) in the gemcitabine group and 5·6 months (3·0-7·0) in the fluorouracil group (hazard ratio [HR] 0·55 [95% CI 0·44-0·68]; p<0·0001). A total of 180 patients in the gemcitabine group and 173 patients in the fluorouracil group were included in the safety analysis. Significantly different treatment-related grade 3 or 4 adverse events between the gemcitabine and fluorouracil groups were leucopenia (52 [29%] vs 15 [9%]; <0·0001), neutropenia (41 [23%] vs 23 [13%]; p=0·0251), thrombocytopenia (24 [13%] vs three [2%]; p=0·0007), and mucosal inflammation (0 vs 25 [14%]; <0·0001). Serious treatment-related adverse events occurred in seven (4%) patients in the gemcitabine group and ten (6%) in the fluorouracil group. Six (3%) patients in the gemcitabine group and 14 (8%) patients in the fluorouracil group discontinued treatment because of drug-related adverse events. No treatment-related deaths occurred in either group., Interpretation: Gemcitabine plus cisplatin prolongs progression-free survival in patients with recurrent or metastatic nasopharyngeal carcinoma. The results establish gemcitabine plus cisplatin as the standard first-line treatment option for this population., Funding: Sun Yat-Sen University Clinical Research 5010 Programme, Chinese National Natural Science Foundation project (grant numbers 81372502 and 81201917), the National High Technology Research and Development Program of China (863 program numbers 2012AA02A501 and 2012AA02A502), and the Natural Science Foundation of Guangdong (grant number S2013010016564)., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The present study was carried out to investigate the prognostic factors in patients who received intra-arterial infusion for advanced pancreatic cancer. In addition, the detailed procedure of intra-arterial infusion chemotherapy was described. A total of 354 patients with advanced unresectable pancreatic adenocarcinoma were recruited from January 2012, to April 2015, at Zhongshan Hospital Fudan University, Shanghai, China. Demographic and clinic characteristics of the patients were extracted from electronic medical records. Restricted cubic spline was used to assess the nonliner regression between baseline CA19-9 value and overall survival. Kaplan-Meier analysis and Cox proportional hazard models were used to estimate the association between overall survival and clinical characteristics. Of all 354 included patients, 230 (65%) were male (male/female ratio = 1.8), and 72 (20%) patients were diagnosed with detectable distant metastases. Pretreatment CA19-9 value of patients with metastases was significantly higher as compared to those with locally advanced cancer (median: 922.30 vs 357.00 U/mL, P = 0.0090). Totally 274 patients completed 1 cycle of intra-arterial infusion, whereas 80 patients received 2 or more cycles of the chemotherapy. For all the 354 patients, median OS was 7.0 months (95% CI: 6.0, 8.0 months) with a 6-, 12-, and 18-month survival rate of 0.48, 0.28, and 0.18, respectively. The median OS of patients, who received 1 cycle of intra-arterial infusion therapy, was 6.0 months (95% CI: 5.0, 8.0 months), which was similar to 7.0 months (95% CI: 6.0, 9.0 months) in patients who received 2 or more cycles. Restricted cubic spline revealed the nonline association between baseline CA19-9 and prognosis. The Cox proportional hazard model showed that age, CA19-9 baseline, CA19-9 value, and tumor location were significantly associated with the OS. In conclusion, the gemcitabine-based RIAC presented a potential treatment method for advanced pancreatic adenocarcinoma. Young age, pretreatment CA19-9 value <1000 U/mL, and tumor located at the head of pancreas indicated better response to the regional intra-arterial chemotherapy and better overall survival.

Background: Platinum chemotherapy has a role in the treatment of metastatic triple-negative breast cancer but its full potential has probably not yet been reached. We assessed whether a cisplatin plus gemcitabine regimen was non-inferior to or superior to paclitaxel plus gemcitabine as first-line therapy for patients with metastatic triple-negative breast cancer., Methods: For this open-label, randomised, phase 3, hybrid-designed trial undertaken at 12 institutions or hospitals in China, we included Chinese patients aged 18-70 years with previously untreated, histologically confirmed metastatic triple-negative breast cancer, and an ECOG performance status of 0-1. These patients were randomly assigned (1:1) to receive either cisplatin plus gemcitabine (cisplatin 75 mg/m(2) on day 1 and gemcitabine 1250 mg/m(2) on days 1 and 8) or paclitaxel plus gemcitabine (paclitaxel 175 mg/m(2) on day 1 and gemcitabine 1250 mg/m(2) on days 1 and 8) given intravenously every 3 weeks for a maximum of eight cycles. Randomisation was done centrally via an interactive web response system using block randomisation with a size of eight, with no stratification factors. Patients and investigator were aware of group assignments. The primary endpoint was progression-free survival and analyses were based on all patients who received at least one dose of assigned treatment. The margin used to establish non-inferiority was 1·2. If non-inferiority of cisplatin plus gemcitabine compared with paclitaxel plus gemcitabine was achieved, we would then test for superiority. The trial is registered with ClinicalTrials.gov, number NCT01287624., Findings: From Jan 14, 2011, to Nov 14, 2013, 240 patients were assessed for eligibility and randomly assigned to treatment (120 in the cisplatin plus gemcitabine group and 120 in the paclitaxel plus gemcitabine group). 236 patients received at least one dose of assigned chemotherapy and were included in the modified intention-to-treat analysis (118 per group). After a median follow-up of 16·3 months (IQR 14·4-26·8) in the cisplatin plus gemcitabine group and 15·9 months (10·7-25·4) in the paclitaxel plus gemcitabine group, the hazard ratio for progression-free survival was 0·692 (95% CI 0·523-0·915; pnon-inferiority<0·0001, psuperiority=0·009, thus cisplatin plus gemcitabine was both non-inferior to and superior to paclitaxel plus gemcitabine. Median progression-free survival was 7·73 months (95% CI 6·16-9·30) in the cisplatin plus gemcitabine group and 6·47 months (5·76-7·18) in the paclitaxel plus gemcitabine group. Grade 3 or 4 adverse events that differed significantly between the two groups included nausea (eight [7%] vs one [<1%]), vomiting (13 [11%] vs one [<1%]), musculoskeletal pain (none vs ten [8%]), anaemia (39 [33%] vs six [5%]), and thrombocytopenia (38 [32%] vs three [3%]), for the cisplatin plus gemcitabine compared with the paclitaxel plus gemcitabine groups, respectively. In addition, patients in the cisplatin plus gemcitabine group had significantly fewer events of grade 1-4 alopecia (12 [10%] vs 42 [36%]) and peripheral neuropathy (27 [23%] vs 60 [51%]), but more grade 1-4 anorexia (33 [28%] vs 10 [8%]), constipation (29 [25%] vs 11 [9%]), hypomagnesaemia (27 [23%] vs five [4%]), and hypokalaemia (10 [8%] vs two [2%]). Serious drug-related adverse events were seen in three patients in the paclitaxel plus gemcitabine group (interstitial pneumonia, anaphylaxis, and severe neutropenia) and four in the cisplatin plus gemcitabine group (pathological bone fracture, thrombocytopenia with subcutaneous haemorrhage, severe anaemia, and cardiogenic syncope). There were no treatment-related deaths., Interpretation: Cisplatin plus gemcitabine could be an alternative or even the preferred first-line chemotherapy strategy for patients with metastatic triple-negative breast cancer., Funding: Shanghai Natural Science Foundation., (Copyright © 2015 Elsevier Ltd. All rights reserved.)