Randomized phase III study of exatecan and gemcitabine compared with gemcitabine alone in untreated advanced pancreatic cancer Journal Article
| Authors: | Abou-Alfa, G. K.; Letourneau, R.; Harker, G.; Modiano, M.; Hurwitz, H.; Tchekmedyian, N. S.; Feit, K.; Ackerman, J.; De Jager, R. L.; Eckhardt, S. G.; O'Reilly, E. M. |
| Article Title: | Randomized phase III study of exatecan and gemcitabine compared with gemcitabine alone in untreated advanced pancreatic cancer |
| Abstract: | Purpose: Exatecan mesylate is a hexacyclic, water-soluble, topoisomerase-1 inhibitor. Exatecan has single-agent and combination activity with gemcitabine in advanced pancreatic cancer. A multicenter, randomized, phase III trial comparing exatecan plus gemcitabine versus gemcitabine alone in advanced pancreatic cancer was conducted. Patients and Methods: Eligibility criteria included Karnofsky performance status ≥ 60%, locally advanced or metastatic pancreatic adenocarcinoma, and no prior chemotherapy. Radiation alone for locally advanced disease was permitted. Patients were randomly assigned on a 1:1 basis. For the exatecan plus gemcitabine arm, exatecan 2.0 mg/m2 and gemcitabine 1,000 mg/m2 were administered on days 1 and 8, every 3 weeks. Gemcitabine alone was dosed at 1,000 mg/m2 up to 7 weeks in the first cycle, then once a week for the first 3 weeks of a 4-week cycle. Tumor assessment was performed every 6 weeks. The primary end point was overall survival. An intent-to-treat analysis was used. Results: From August 2001 to January 2003, 349 patients were randomly assigned, 175 to exatecan plus gemcitabine and 174 to gemcitabine alone. Twenty-four patients (6.9%) were not treated. The median survival time was 6.7 months for exatecan plus gemcitabine and 6.2 months for gemcitabine alone (P = .52). One complete response (CR; < 1%) and 11 partial responses (PRs; 6.3%) were observed in the exatecan plus gemcitabine treatment group, and one CR (< 1%) and eight PRs (4.6%) were observed in the gemcitabine-alone group. Grade 3 and 4 toxicities were higher for the exatecan plus gemcitabine arm versus the gemcitabine alone arm; neutropenia (30% v 15%) and thrombocytopenia (15% v 4%). Conclusion: Exatecan plus gemcitabine was not superior to gemcitabine alone with respect to overall survival in the first-line treatment of advanced pancreatic cancer. © 2006 by American Society of Clinical Oncology. |
| Keywords: | survival; adult; cancer survival; controlled study; treatment outcome; aged; aged, 80 and over; disease-free survival; middle aged; survival analysis; major clinical study; clinical trial; fatigue; neutropenia; drug efficacy; drug safety; gemcitabine; disease free survival; pancreas cancer; pancreatic neoplasms; antineoplastic agent; demography; controlled clinical trial; multiple cycle treatment; antimetabolites, antineoplastic; nausea; randomized controlled trial; thrombocytopenia; antineoplastic combined chemotherapy protocols; drug administration schedule; antineoplastic agents, phytogenic; camptothecin; pathology; pancreas tumor; drug derivative; pancreas adenocarcinoma; phase 3 clinical trial; drug administration; deoxycytidine; antineoplastic antimetabolite; race difference; exatecan |
| Journal Title: | Journal of Clinical Oncology |
| Volume: | 24 |
| Issue: | 27 |
| ISSN: | 0732-183X |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 2006-09-20 |
| Start Page: | 4441 |
| End Page: | 4447 |
| Language: | English |
| DOI: | 10.1200/jco.2006.07.0201 |
| PUBMED: | 16983112 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 107" - "Export Date: 4 June 2012" - "CODEN: JCOND" - "Source: Scopus" |
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