A phase II study of gemcitabine and cisplatin plus sorafenib in patients with advanced biliary adenocarcinomas Journal Article
| Authors: | Lee, J. K.; Capanu, M.; O'Reilly, E. M.; Ma, J.; Chou, J. F.; Shia, J.; Katz, S. S.; Gansukh, B.; Reidy-Lagunes, D.; Segal, N. H.; Yu, K. H.; Chung, K. Y.; Saltz, L. B.; Abou-Alfa, G. K. |
| Article Title: | A phase II study of gemcitabine and cisplatin plus sorafenib in patients with advanced biliary adenocarcinomas |
| Abstract: | Background: This study evaluated the addition of sorafenib to gemcitabine and cisplatin in biliary adenocarcinoma first-line therapy. Methods: Patients with advanced biliary adenocarcinomas received gemcitabine 1000 mg m-2 and cisplatin 25 mg m-2 on a 2 weeks on/1 week off cycle and sorafenib 400 mg twice daily. After the initial 16 patients were enrolled, the chemotherapy doses were amended in view of grade 3 and 4 hand-foot skin reaction and haematologic toxicity. Subsequently, 21 patients received gemcitabine 800 mg m-2, cisplatin 20 mg m-2 and sorafenib 400 mg. The primary end point was an improvement in 6-month progression-free survival (PFS6) from historical 57-77% (90% power, type I error of 10%). Pretreatment pERK, evaluated by immunostaining, was correlated with clinical outcome. Results: A total of 39 patients were accrued. The most common grade 3-4 toxicities noted in >10% of patients were fatigue, elevated liver function tests and haematologic toxicities including thromboemboli, hyponatraemia and hypophosphataemia. Six-month progression-free survival was 51% (95% confidence interval (CI) 34-66%). Median PFS and overall survival were 6.5 (95% CI: 3.5-8.3) and 14.4 months (95% CI: 11.6-19.2 months), respectively. No correlation was observed between pERK and outcomes. Conclusion: The addition of sorafenib to gemcitabine and cisplatin in biliary adenocarcinomas did not improve efficacy over historical data, and toxicity was increased. © 2013 Cancer Research UK. All rights reserved. |
| Keywords: | adult; cancer survival; clinical article; treatment outcome; aged; aged, 80 and over; disease-free survival; middle aged; overall survival; fatigue; neutropenia; sorafenib; cisplatin; advanced cancer; cancer combination chemotherapy; drug efficacy; hypophosphatemia; side effect; gemcitabine; adenocarcinoma; progression free survival; liver toxicity; phase 2 clinical trial; anemia; blood toxicity; leukopenia; thrombocytopenia; antineoplastic combined chemotherapy protocols; alanine aminotransferase blood level; aspartate aminotransferase blood level; lymphocytopenia; gastrointestinal toxicity; hyponatremia; correlation analysis; thromboembolism; bile duct carcinoma; bile duct neoplasms; bile ducts, intrahepatic; cholangiocarcinoma; alkaline phosphatase blood level; hyperbilirubinemia; liver function test; gallbladder neoplasms; amylase blood level; hand foot syndrome; triacylglycerol lipase blood level; deoxycytidine; metabolic disorder; biliary tract neoplasms; bile ducts, extrahepatic; niacinamide; phenylurea compounds |
| Journal Title: | British Journal of Cancer |
| Volume: | 109 |
| Issue: | 4 |
| ISSN: | 0007-0920 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2013-08-20 |
| Start Page: | 915 |
| End Page: | 919 |
| Language: | English |
| DOI: | 10.1038/bjc.2013.432 |
| PROVIDER: | scopus |
| PMCID: | PMC3749586 |
| PUBMED: | 23900219 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 1 October 2013" - "CODEN: BJCAA" - "Source: Scopus" |
