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Introduction: Hepatic arterial infusion chemotherapy (HAIC) with cisplatin and lenvatinib exhibits strong antitumor effects against advanced hepatocellular carcinoma (HCC). Higher antitumor activity is expected for the combination treatment. The aim of this trial was to evaluate the efficacy and safety of lenvatinib in combination with HAIC using cisplatin in patients with advanced HCC. Methods: In this multicenter, open-labeled, single-arm, phase II trial, patients with advanced HCC categorized as Child-Pugh class A with no prior history of systemic therapy were enrolled. Patients received lenvatinib plus HAIC with cisplatin (lenvatinib: 12 mg once daily for patients ≥60 kg, 8 mg once daily for patients <60 kg; HAIC with cisplatin: 65 mg/m2, day 1, every 4–6 weeks, maximum of six cycles). The primary endpoint was the objective response rate (ORR) assessed using modified RECIST by the Independent Review Committee. The secondary endpoints were the ORR assessed using RECIST v1.1, progression-free survival, overall survival, and frequency of adverse events associated with the treatment. Results: A total of 36 patients were enrolled between September 2018 and March 2020. In the 34 evaluable patients, the ORR assessed by the Independent Review Committee using modified RECIST and RECIST v1.1 were 64.7% (95% confidence interval [CI]: 46.5–80.3%) and 45.7% (95% CI: 28.8–63.4%), respectively. The median progression-free survival and overall survival were 6.3 months (95% CI: 5.1–7.9 months) and 17.2 months (95% CI: 10.9 – not available, months), respectively. The main grade 3–4 adverse events were increased aspartate aminotransferase (34%), leukopenia (22%), increased alanine aminotransferase (19%), and hypertension (11%). Conclusion: Lenvatinib plus HAIC with cisplatin yielded a favorable ORR and overall survival and was well tolerated in patients with advanced HCC. Further evaluation of this regimen in a phase III trial is warranted. [ABSTRACT FROM AUTHOR]

Dear Editor, Recent developments in systemic therapy for hepatocellular carcinoma (HCC) have been outstanding, and a response rate of 40.6% based on the modified RECIST criteria has been reported after lenvatinib (LEN) therapy for advanced HCC [[1]]. Preoperative LEN therapy might be a promising option among the multidisciplinary treatments for HCC with macroscopic HVTT. CT, computed tomography; TT, tumor thrombus; LEN, lenvatinib; IVC, inferior vena cava. [Extracted from the article]

Introduction: Combining an immune checkpoint inhibitor with a targeted antiangiogenic agent may leverage complementary mechanisms of action for the treatment of advanced/metastatic hepatocellular carcinoma (aHCC). Avelumab is a human anti-PD-L1 IgG1 antibody with clinical activity in various tumor types; axitinib is a selective tyrosine kinase inhibitor of vascular endothelial growth factor receptors 1, 2, and 3. We report the final analysis from VEGF Liver 100 (NCT03289533), a phase 1b study evaluating safety and efficacy of avelumab plus axitinib in treatment-naive patients with aHCC. Methods: Eligible patients had confirmed aHCC, no prior systemic therapy, ≥1 measurable lesion, Eastern Cooperative Oncology Group performance status ≤1, and Child-Pugh class A disease. Patients received avelumab 10 mg/kg intravenously every 2 weeks plus axitinib 5 mg orally twice daily until progression, unacceptable toxicity, or withdrawal. Endpoints included safety and investigator-assessed objective response per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and modified RECIST (mRECIST) for HCC. Results: Twenty-two Japanese patients were enrolled and treated with avelumab plus axitinib. The minimum follow-up was 18 months as of October 25, 2019 (data cutoff). Grade 3 treatment-related adverse events (TRAEs) occurred in 16 patients (72.7%); the most common (≥3 patients) were hypertension (n = 11 [50.0%]), palmar-plantar erythrodysesthesia syndrome (n = 5 [22.7%]), and decreased appetite (n = 3 [13.6%]). No grade 4 TRAEs or treatment-related deaths occurred. Ten patients (45.5%) had an immune-related AE (irAE) of any grade; 3 patients (13.6%) had an infusion-related reaction (IRR) of any grade, and no grade ≥3 irAE and IRR were observed. The objective response rate was 13.6% (95% CI: 2.9–34.9%) per RECIST 1.1 and 31.8% (95% CI: 13.9–54.9%) per mRECIST for HCC. Conclusion: Treatment with avelumab plus axitinib was associated with a manageable toxicity profile and showed antitumor activity in patients with aHCC. [ABSTRACT FROM AUTHOR]

Background: Platinum-containing regimens are widely used as first-line chemotherapy for unresectable pancreatic neuroendocrine carcinoma (NEC), but second-line chemotherapies have yet to be established. Objectives: We evaluated the safety and efficacy of everolimus in patients with pancreatic NEC refractory or intolerant to platinum-containing chemotherapy. Methods: This study was a prospective, multicenter, phase II trial in patients with pancreatic NEC after platinum-containing chemotherapy. Everolimus treatment was continued until disease progression or intolerable toxicity was observed. The primary endpoint was progression-free survival (PFS). Results: Participants comprised 25 patients. Median age was 63 years, median PFS was 1.2 months (95% confidence interval [CI] 0.9–3.1 months), median overall survival was 7.5 months (95% CI 3.1–13.5 months), overall response rate was 0%, and disease control rate was 39.1%. Common grade 3/4 adverse events were hyperglycemia (20%), thrombocytopenia (16%), and anemia (16%). Conclusion: The efficacy of everolimus was limited in patients with unresectable pancreatic NEC. [ABSTRACT FROM AUTHOR]

Aim: The purpose of this study was to elucidate the treatment efficacy and safety of gemcitabine monotherapy, and to identify prognostic factors in patients with advanced biliary tract cancer receiving this therapy. Method: The data of 100 patients with advanced biliary tract cancer who were treated with gemcitabine as first-line chemotherapy were reviewed retrospectively. Results: One patient showed complete response (1.0%) and 6 patients showed partial response (6.0%), yielding an overall response rate of 7.0%. The main grade 3/4 toxicities were neutropenia and leukopenia. The median survival, 1-year survival rate and progression-free survival were 7.3 months, 21.6% and 3.1 months, respectively. Multivariate analysis identified a performance status of 0-1, serum C-reactive protein level of <3.0 mg/dl, serum carcinoembryonic antigen level of <10 ng/ml and serum albumin level of ≥3.5 g/dl as factors independently associated with a favorable prognosis. Conclusions: Gemcitabine monotherapy showed modest efficacy with manageable toxicity in patients with biliary tract cancer. These results could be useful as reference data for optimizing treatment strategies and planning future clinical trials in patients with advanced biliary tract cancer. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to determine the maximum-tolerated dose and dose-limiting toxicity (DLT) of combination therapy with gemcitabine and S-1 in patients with advanced pancreatic cancer. Methods: Chemotherapy-naive patients with histologically or cytologically proven unresectable or metastatic pancreatic cancer were enrolled. The patients received gemcitabine intravenously over 30 min on days 1 and 8 and S-1 orally twice daily from days 1 to 14. Cycles were repeated every 21 days until disease progression. Patients were scheduled to receive gemcitabine (mg/m2/week) and S-1 (mg/m2/day) at four dose levels: 800/60 (level 1), 1,000/60 (level 2), 1,000/70 (level 3) and 1,000/80 (level 4). Results: Eighteen patients were enrolled in this study. The maximum-tolerated dose was not reached even at the highest dose level (level 4) because only 2 of the 6 patients at this level experienced DLT. The DLTs were neutropenia and rash. Six (33%) of the 18 patients achieved a partial response and median overall survival time was 7.6 months. Conclusions: Combination chemotherapy with gemcitabine and S-1 was well tolerated and showed good antitumor activity in the treatment of pancreatic cancer. We recommend a gemcitabine dose of 1,000 mg/m2/week and an S-1 dose of 80 mg/m2/day in further studies with this schedule. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: To clarify the role of chemotherapy for advanced gallbladder cancer (GBC). Methods: We reviewed 89 GBC patients: 21 admitted before 1997 were treated with a combination of cisplatin, epirubicin, and 5-fluorouracil (CEF); 25, admitted subsequently, received a combination of 5-fluorouracil, doxorubicin and mitomycin (FAM), and the remaining 43, ineligible for these trials, received supportive care. We investigated the relation between pretreatment clinical variables and long-term survival in these 89 subjects, and analyzed whether chemotherapy could favor longer survival. Results: There were no significant differences in survival time between the chemotherapy groups, whereas the response rate to the CEF regimen was 4-fold higher than to the FAM regimen (32 vs. 8%). Subgroup analysis suggested that chemotherapy favored longer survival in patients with a performance status (PS) of 0 or 1, but not in patients with a PS of 2. Cox regression analysis suggested a significant hazard reduction by chemotherapy in patients with a PS of 0 or 1, but not in patients with a PS of 2. Conclusions: GBC patients with poor PS should not be treated with chemotherapy at present. It is essential to design good clinical trials and develop more effective chemotherapy regimens. Copyright © 2004 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]