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 > or = 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.

• Authors: Ghassan K Abou-Alfa, Richard Letourneau, Graydon Harker, Manuel Modiano, Herbert Hurwitz, Nerses Simon Tchekmedyian, Kevie Feit, Judie Ackerman, Robert L De Jager, S Gail Eckhardt, Eileen M O'Reilly
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 24 Issue 27 Pg. 4441-7 (Sep 20 2006) ISSN: 1527-7755 [Electronic] United States
• PMID: 16983112 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antimetabolites, Antineoplastic
• Antineoplastic Agents, Phytogenic
• Deoxycytidine
• exatecan
• Camptothecin
• Gemcitabine

Topics

• Adult
• Aged
• Aged, 80 and over
• Antimetabolites, Antineoplastic (administration & dosage, therapeutic use)
• Antineoplastic Agents, Phytogenic (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Camptothecin (administration & dosage, analogs & derivatives)
• Deoxycytidine (administration & dosage, analogs & derivatives, therapeutic use)
• Disease-Free Survival
• Drug Administration Schedule
• Female
• Humans
• Male
• Middle Aged
• Pancreatic Neoplasms (drug therapy, pathology)
• Survival Analysis
• Treatment Outcome
• Gemcitabine