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Background: This network meta-analysis (NMA) aims to provide evidence-based guidance for selecting the second-line chemotherapy for biliary tract cancer (BTC)., Methods: A comprehensive literature search was conducted on PubMed, Cochrane, and EMBASE through July 2024. Inclusion criteria involved: (1) patients underwent second-line chemotherapy following platinum-based first-line therapy, (2) intervention/comparator groups consisted of various chemotherapeutic agents, and (3) outcomes measured as hazard ratio (HR) of overall survival (OS) and progression-free survival (PFS) in randomized controlled trials (RCTs) and cohort studies., Results: Outcomes were measured as HR of OS and PFS in RCTs and cohort studies. The eight studies consisting of 1621 patients were selected. In the NMA for OS, 5FU_plus_Plat (fluorouracil plus oxaliplatin or cisplatin; HR 0.52, 95% confidence interval [CI]: 0.30-0.91), nal-IRI_5FU_LV (nano-liposomal irinotecan plus fluorouracil and LV; HR 0.54 [95% CI: 0.32-0.92]), and FOLFOX (fluorouracil plus oxaliplatin; HR 0.69 [95% CI: 0.50-0.96]) demonstrated significant benefits in OS when compared to control. For PFS, nal-IRI_5FU_LV (HR 0.61 [95% CI: 0.44-0.85]) provided a significant advantage over 5FU., Conclusions: Second-line chemotherapy for BTC after the failure of gemcitabine plus platinum as first-line therapy, nal-IRI_5FU_LV appears to be the most promising second-line therapy in terms of both OS and PFS., (© 2025 Japanese Society of Hepato‐Biliary‐Pancreatic Surgery.)

Epithelial ovarian cancer has the highest mortality among all gynecological malignancies. The main reasons for high mortality are late diagnosis and development of resistance to chemotherapy. Resistance to chemotherapeutic drugs can result from altered expression of drug-resistance genes regulated by miRNA. The main goal of our study was to detect differences in miRNA expression levels in two doxorubicin (DOX)- and two topotecan (TOP)-resistant variants of the A2780 drug-sensitive ovarian cancer cell line by miRNA microarray. The next aim was to recognize miRNAs as factors responsible for the regulation of drug-resistance genes. We observed altered expression of 28 miRNA that may be related to drug resistance. The upregulation of miR-125b-5p and miR-935 and downregulation of miR-218-5p was observed in both DOX-resistant cell lines. In both TOP-resistant cell lines, we noted the overexpression of miR-99a-5p, miR-100-5p, miR-125b-5p, and miR-125b-2-3p and decreased expression of miR-551b-3p, miR-551b-5p, and miR-383-5p. Analysis of the targets suggested that expression of important drug-resistant genes such as the collagen type I alpha 2 chain ( COL1A2 ), protein Tyrosine Phosphatase Receptor Type K ( PTPRK ), receptor tyrosine kinase- EPHA7 , Roundabout Guidance Receptor 2 ( ROBO2 ), myristoylated alanine-rich C-kinase substrate ( MARCK ), and the ATP-binding cassette subfamily G member 2 ( ABCG2 ) can be regulated by miRNA.

Maintenance chemotherapy was studied in first line setting for advanced stage non-small cell lung carcinoma (NSCLC). There has not been any data on the role of continuation maintenance chemotherapy in second line setting. A retrospective cohort study that included 226 patients with advanced stage NSCLC that received second line gemcitabine ± platinum was conducted. Patients who had continuation maintenance gemcitabine were compared with those who went on drug holiday. The primary endpoint was progression-free survival (PFS), counted from the end of induction therapy. The median PFS was significantly longer for patients who continued with maintenance gemcitabine when compared with those on drug holiday (5.6 vs 1.7 months, HR 0.392, p-value < 0.001). The overall survival was also significantly longer (21.4 vs 15.8 months, HR 0.508, p-value 0.047). There was no increase in incidence of adverse events for patients who underwent maintenance gemcitabine. Continuation maintenance therapy with gemcitabine in second line setting is a potentially feasible and safe option for patients with advanced NSCLC.

Background: Data on FOLFIRINOX as a second-line chemotherapy for advanced pancreatic cancer are limited. In the JASPAC06 study-a nationwide, multicenter, observational study-FOLFIRINOX for patients with unresectable or recurrent pancreatic cancer as any line of treatment showed favorable efficacy and safety in Japanese clinical practice., Methods: We performed exploratory analyses of patients with unresectable or recurrent pancreatic cancer who received FOLFIRINOX as the second-line chemotherapy in Japanese clinical settings., Results: Of the 399 evaluable patients, 44 were eligible for inclusion in the analysis. The patients' characteristics were as follows: median age, 62 years; men, 26 (59%); Eastern Cooperative Oncology Group-Performance status 0/1, 30 (68%)/14 (32%); disease status, recurrent/local/metastatic: 4 (9%)/8 (18%)/32 (73%). The initial dose was reduced in 28 (64%) patients. The median time to treatment failure and number of cycles were 4.5 (range, 0.2-19.1) months and 6 cycles (range, 1-13 or more), respectively. The major grade 3/4 adverse events were neutropenia in 29 (66%), leucopenia in 17 (39%), anorexia in 7 (16%), febrile neutropenia in 5 (11%), and anemia in 5 (11%) patients. The median overall survival, progression-free survival, and 1-year survival rates were 10.3 (95% confidence interval [CI], 7.2-13.3), 4.1 (95% CI, 2.6-5.5) months, and 30%, respectively., Conclusion: Our findings suggest that FOLFIRINOX as a second-line chemotherapy for advanced pancreatic cancer was effective in patients with a good performance status. It displayed toxicity similar to that observed with its use as a first-line treatment., (Copyright © 2020. Published by Elsevier B.V.)

Background/Aims: The benefit of second-line chemotherapy (SL) after failed first-line chemotherapy (FL) in patients with advanced pancreatic cancer has not yet been established. We evaluated the clinical characteristics affecting the benefits of SL compared to best supportive care (BSC), identified the prognostic factors, and ultimately devised a model of clinical parameters to assist in making decision between SL and BSC after the failure of gemcitabine-based FL. Methods: The records of patients who received gemcitabinebased FL for advanced pancreatic cancer at Yonsei University Hospital between January 2010 and December 2015 were retrospectively reviewed. Significant clinical parameters were assessed for their potential as predictive factors. Results: SL patients received a longer duration of FL compared with BSC patients with median duration being 16.0 weeks (range, 8.0 to 26.0 weeks) and 8.0 weeks (range, 4.0 to 16.0 weeks), respectively (p<0.001). When the SL group was stratified by their modified overall survival (mOS) (longer and shorter than 6 months), we found significant differences for several clinical factors, namely, metastasis to the peritoneum (p<0.001), number of metastases (p<0.001), thrombotic events (p=0.003), and level of carbohydrate antigen 19-9 (CA19- 9; p=0.011). In multivariate analysis, more than one site of metastasis, occurrence of thrombotic event during FL, and a CA19-9 level above 90 U/mL were significant independent prognostic factors for mOS in the SL group (p<0.05). When an attempt was made to devise a prognostic nomogram, Harrell's C-index of the final prognosis prediction model was 0.62. Conclusions: SL may be beneficial for patients without peritoneal metastasis or thrombotic events who have a single metastasis and a level of CA19-9 less than 90 U/mL. This prognostic nomogram can be used to predict mOS before the administration of SL after the failure of gemcitabinebased FL.

The purpose of this study was to identify previous treatments and biomarker profile features that prognosticate overall survival (OS) in patients with mCRPC receiving 177 Lu-PSMA-617. Methods: 109 mCRPC patients treated with a median of 3 cycles of 177 Lu-PSMA-617 were included. Data were analyzed according to OS as well as PSA response patterns with regard to prior therapies, laboratory biomarkers and metastatic extent in univariate as well as multivariate Cox's proportional hazards models. PSA decline was assessed using the lowest PSA levels after the first cycle of therapy (initial PSA response) and during the entire observation period (best PSA response). Results: In total, 54 patients (49.5%) died during the observation period. First and second line chemotherapy were performed in 85% and 26%, and Abiraterone and Enzalutamide were administered in 83% and 85%, respectively. Any initial PSA decline occurred in 55% while 25% showed a PSA decline of ≥50%. The median estimated OS was 9.9 months (95% CI: 7.2-12.5) for all patients. Any initial decline of PSA was associated with significantly prolonged OS (15.5 vs. 5.7 months, p = 0.002). Second line cabazitaxel chemotherapy (6.7 vs. 15.7 months, p = 0.002) and presence of visceral metastases (5.9 vs. 16.4 months, p <0.001) were associated with shorter OS. Only visceral metastases remained significant in a multivariate analysis. Conclusion: Lu-PSMA-617 is an effective therapy for patients with mCRPC. However, the present data indicate that its beneficial effects on OS are strongly influenced by pretreatment (history of second line chemotherapy with cabazitaxel) and the presence of visceral metastases at onset of 177 Lu-PSMA-617 is an effective therapy for patients with mCRPC. However, the present data indicate that its beneficial effects on OS are strongly influenced by pretreatment (history of second line chemotherapy with cabazitaxel) and the presence of visceral metastases at onset of 177 Lu-PSMA-617 treatment., Competing Interests: Competing Interests: The University of Münster received consulting fees from ABX GmbH, Radeberg, Germany for K.R. and M.B. Additionally K.R. is scientific consultant/ advisor of ABX GmbH. The authors declare they have no conflict of interest according to the subject and matter of the present article.

There are not established treatments for patients with advanced malignant pleural mesothelioma that progressed after first-line chemotherapy with cisplatin and pemetrexed. Retrospective analyses suggest a possible role for rechallenge with pemetrexed for selected patients. Phase II trials demonstrate a modest efficacy of vinorelbine monotherapy with a response rate ranging between 0% and 18% and a tolerable toxicity profile. Combination schedules, despite an increased toxicity, fail to demonstrate an improved efficacy. To date, genome wide analyses did not show molecular targets suitable for therapy and biological drugs did not exert a significant efficacy in clinical trials. Immunotherapy has given a hint of efficacy in early clinical trials but definitive evaluations are still ongoing., Competing Interests: Conflict of Interest: The authors have no conflicts of interest to declare.

Background/aims: The purpose of this study was to investigate the efficacy and safety of irinotecan based FOLFIRI chemotherapy as a second-line treatment after failure of FOLFOX-4 chemotherapy in patients with advanced gastric cancer., Methods: Fifty-two patients who were pathologically diagnosed with unresectable gastric cancer and received FOLFIRI chemotherapy after failure of FOLFOX-4 chemotherapy between September 2005 and February 2012 were enrolled in this study. Data were collected by retrospectively reviewing the medical records. The response to chemotherapy was assessed every 3 cycles by World Health Organization criteria and long term survival was analyzed. The toxicities were evaluated for every course of chemotherapy according to National Cancer Institution (NCI) toxicity criteria version 3.0., Results: Median age of the patients was 57 years. Median overall survival (OS) and time to progression (TTP) were 7.8 and 5 months, respectively. The number of patients showing complete remission, partial remission, stable disease, and progressive disease were 0 (0.0%), 9 (17.3%), 30 (57.7%), and 13 (25.0%), respectively. The overall response rate was 17.3%. During a total of 345 cycles, anemia worse than NCI toxicity grade 3 occurred in 2.9%, leukopenia in 20.3%, neutropenia in 12.2%, and thrombocytopenia in 1.5%. Patients with less organ involvement by metastasis, less than 34 U/mL of CA 19-9 and good responsiveness to third cycle of second line chemotherapy were associated with longer OS and TTP., Conclusions: FOLFIRI chemotherapy has a modest efficacy with acceptable toxicities in patients with advanced gastric cancer as a second-line treatment. Further well-controlled studies are needed to elucidate the efficacy of FOLFIRI chemotherapy as second-line treatment in patients with advanced stomach cancer.

Background: We have previousy reported on a Phase II study of S-1 monotherapy as a first line, combination therapy of S-1 plus cisplatin as a second line, and weekly paclitaxel monotherapy as a third line therapy in patients with advanced gastric carcinomas. The median survival time (MST) of patients over the whole course of treatment was not previously calculated because 12 out of 19 patients had not yet succumbed. Since then, we have calculated the MST for this study and herein report our findings., Patients and Methods: Between 2002 and 2005, 19 patients were enrolled in this study. Chemotherapy consisted of either 60 mg/m(2) of S-1 for 4 weeks at 6-week intervals, a combination of 60 mg/m(2) S-1 for 3 weeks and 60 mg/m(2) cisplatin on day 8 at 5-week intervals, or 60 mg/m(2) paclitaxel at days 1, 8, and 15, at 4-week intervals. The regimens were repeated until the occurrence of unacceptable toxicities, disease progression, or patient noncompliance. The primary end point was the overall survival., Results: The median survival time was 774 days. The response rates were 33.3% (3/9), 12.5% (1/8), and 0% (0/4) after the first, second, and third line chemotherapies, respectively. The major adverse hematological toxicity was leukopenia, which reached grades 3-4 in all lines of chemotherapy investigated. In addition, the major adverse non-hematological toxicity was anorexia, which reached grade 3-4 in second line chemotherapy, and no deaths were attributable to the adverse effects of the drugs., Conclusion: This sequential therapy was an effective treatment for advanced gastric cancer with acceptable toxic side-effects. We considered this therapy to be effective because of the smooth transition to the next regimen.

Purpose: With the increased use of chemotherapy for non small cell lung cancer (NSCLC), a growing group of patients can now be considered for second-line chemotherapy. However, guidelines for the second line treatment remain to be developed. The objective of this study was to evaluate the efficacy and safety of the gemcitabine and vinorelbine combination therapy in patients with advanced NSCLC, pretreated with taxane and platinum based regimens. Gemcitabine has already demonstrated activity in this patient group, with the combination therapy having been reported to be well tolerated in previous phase I/II studies., Materials and Methods: Forty two patients with advanced NSCLC (stages III/IV), having received prior taxane and platinum based chemotherapy, with an ECOG performance status (PS) 0~2, and unimpaired hematopoietic and organ function, were treated with vinorelbine, 20 mg/m2, followed by gemcitabine, 1, 000 mg/m2, both administered on days 1, 8 and 15, every 4 weeks., Results: Out of the 42 patients enrolled, 41 were evaluable for their response, and all 42 for their toxicity. The patient's characteristics were as follows; median age=60 years (42~73), median PS=1 (range 0~2), a gender ratio 31: 11 males/females, with stages IIIA, IIIB and IV in 3, 14 and 25 cases. The objective responses included a partial response (PR) 8/41 (19.5%), a stable disease 15/41 (36.6%) and a progressive disease 18/41 (43.9%). The median time-to progression (TTP) and survival were 4 months, ranging from 2 to 14 months, and 8 months, ranging from 2 to 17+ months, respectively. Grade 3 neutropenia was seen in 19% of the patient, and there was no grade 4 neutropenia or episodes of febrile neutropenia. No grade 4 thrombocytopenia or other grade 3/4 non-hematological toxicities were observed., Conclusion: The combination of gemcitabine/vinorelbine is active and well tolerated in patients with advanced NSCLC having failed prior taxane/platinum therapy.