A multicenter phase II study of irinotecan (CPT-11) alternated with 5-fluorouracil and leucovorin as first-line treatment of patients with metastatic colorectal cancer

Cancer Chemother Pharmacol. 2003 Oct;52(4):339-45. doi: 10.1007/s00280-003-0601-4. Epub 2003 Jul 8.

Abstract

Purpose: In this multicenter phase II study the efficacy and safety of the alternating schedule of irinotecan (CPT-11) with bolus 5-fluorouracil (5-FU) and leucovorin (LV) were assessed as first-line chemotherapy in patients with metastatic colorectal cancer (CRC).

Patients and methods: Enrolled in the study were 43 patients with advanced CRC. They received CPT-11 350 mg/m2 i.v. on day 1, alternating with LV 20 mg/m2 i.v. and 5-FU 425 mg/m2 i.v. daily for five consecutive days, on days 22-26 (Mayo Clinic regimen). One cycle consisted of 6 weeks.

Results: A total of 179 cycles were administered with a median of four per patient (range one to nine). Efficacy was analyzed on an intention-to-treat basis. The overall objective response rate was 30% (95% CI 16-44), with four complete responses and nine partial responses, whereas 20 patients (4%) showed stable disease. The median time to disease progression was 9.0 months and median survival was 18.5 months. Grade 3/4 diarrhea was mainly related to CPT-11 rather than to 5-FU (9.3% vs 4.7% of patients), whereas grade 3/4 neutropenia was higher during 5-FU administration (16.3% vs 7.0% of patients).

Conclusions: The alternating schedule of CPT-11 with 5 days bolus of 5-FU and low-dose LV showed a clinical benefit in terms of tumor growth control as first-line treatment of patients with metastatic CRC. The overall safety data confirmed this alternating combination as a well-tolerated treatment.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antidotes / therapeutic use*
  • Antimetabolites, Antineoplastic / adverse effects
  • Antimetabolites, Antineoplastic / therapeutic use*
  • Antineoplastic Agents, Phytogenic / adverse effects
  • Antineoplastic Agents, Phytogenic / therapeutic use*
  • Camptothecin / adverse effects
  • Camptothecin / analogs & derivatives*
  • Camptothecin / therapeutic use*
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / pathology
  • Female
  • Fluorouracil / adverse effects
  • Fluorouracil / therapeutic use*
  • Humans
  • Infusions, Intravenous
  • Irinotecan
  • Leucovorin / therapeutic use*
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Survival Analysis

Substances

  • Antidotes
  • Antimetabolites, Antineoplastic
  • Antineoplastic Agents, Phytogenic
  • Irinotecan
  • Leucovorin
  • Fluorouracil
  • Camptothecin