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/m 2 and gemcitabine 1,000 mg/m 2 were administered on days 1 and 8, every 3 weeks. Gemcitabine alone was dosed at 1,000 mg/m 2 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.

Keywords

GemcitabineMedicinePancreatic cancerInternal medicineClinical endpointChemotherapyDeoxycytidineAntimetabolitePhases of clinical researchOncologyGastroenterologyCancerRandomized controlled trial

MeSH Terms

AdultAgedAged80 and overAntimetabolitesAntineoplasticAntineoplastic AgentsPhytogenicAntineoplastic Combined Chemotherapy ProtocolsCamptothecinDeoxycytidineDisease-Free SurvivalDrug Administration ScheduleFemaleHumansMaleMiddle AgedPancreatic NeoplasmsSurvival AnalysisTreatment OutcomeGemcitabine

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Publication Info

Year
2006
Type
article
Volume
24
Issue
27
Pages
4441-4447
Citations
277
Access
Closed

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Cite This

Ghassan K. Abou‐Alfa, Richard Létourneau, Graydon Harker et al. (2006). Randomized Phase III Study of Exatecan and Gemcitabine Compared With Gemcitabine Alone in Untreated Advanced Pancreatic Cancer. Journal of Clinical Oncology , 24 (27) , 4441-4447. https://doi.org/10.1200/jco.2006.07.0201

Identifiers

DOI
10.1200/jco.2006.07.0201
PMID
16983112

Data Quality

Data completeness: 86%