A phase 1 study of fixed dose rate gemcitabine and irinotecan in patients with advanced pancreatic and biliary cancer

Weijing Sun, Maureen R. Hewitt, Marry R. Theobald, Diane Hershock, Daniel G. Haller

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

BACKGROUND. The combination of a fixed dose rate (FDR) infusion of gemcitabine and irinotecan may have a synergistic effect in the treatment of patients with advanced and metastatic pancreatic and biliary cancer. The current study was conducted to determine the dose-limiting toxicity (DLT) and the maximum tolerated dose (MTD) of the combination. METHODS. There were 32 patients with metastatic pancreatic and advanced unresectable/metastatic biliary adenocarcinoma who were entered into this open-label, phase 1 dose escalation trial. Gemcitabine was administered at an FDR of 10 mg/m2/minute intravenously (iv). Irinotecan was administered iv over 60 minutes after gemcitabine. Both gemcitabine and irinotecan were given on Days 1 and 8 of a 21-day cycle. RESULTS. The MTD of the combination was gemcitabine at an FDR of 1200 mg/m2 and irinotecan at a dose of 100 mg/m2. The DLTs were neutropenia and neutropenic fever. Other DLTs included diarrhea, dehydration, and fatigue. Two patients developed deep venous thrombosis during the treatment. The efficacy of the combination was encouraging, even at the lower dose levels. Of 30 assessable patients, there was 1 complete response, 6 partial responses, and 16 patients with stable disease, with a response rate of 23%, a disease control rate of 76%, a median progression-free survival of 4.7 months, and a median overall survival of 7.0 months. The average number of treatment cycles received was 11. CONCLUSIONS. The recommended doses of the combination for future study are gemcitabine at an FDR of 1200mg/m2 and irinotecan at a dose of 100 mg/m2. The efficacy of the combination is encouraging. Further assessment of the combination with or without biologic agents is suggested.

Original languageEnglish (US)
Pages (from-to)2768-2774
Number of pages7
JournalCancer
Volume110
Issue number12
DOIs
StatePublished - Dec 15 2007

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'A phase 1 study of fixed dose rate gemcitabine and irinotecan in patients with advanced pancreatic and biliary cancer'. Together they form a unique fingerprint.

Cite this