A phase I study of sequential irinotecan and 5-fluorouracil/leucovorin

R. M. Goldberg, S. H. Kaufmann, P. Atherton, J. A. Sloan, A. A. Adjei, H. C. Pitot, S. R. Alberts, J. Rubin, L. L. Miller, C. Erlichman

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Background: Irinotecan (CPT-11) and 5–fluorouracil (5–FU)/leucovorin are active agents in colorectal cancer. A sequence-dependent synergism of SN–38 followed by 5–FU/leucovorin in vitro led us to conduct a phase I trial of CPT–11 followed by 5–FU/leucovorin to determine the maximum tolerated dose (MTD) and toxicities of this regimen and to obtain preliminary indications of its activity in patients with advanced solid tumors. Patients and methods: Fifty-six patients were enrolled in sequential cohorts to receive escalating doses of CPT–11 (90 min infusion) on day 1, followed by leucovorin 20 m/m2 (intravenous push) and 5–FU (90 min infusion) on days 2–5 of each 21–day cycle. Results: A total of 347 treatment cycles (median 4, range 1–25) were administered. Dose-limiting toxicities were diarrhea, neutropenia and fatigue. Nine patients with colorectal cancer and one with gastric cancer had partial or minor responses. Eight of the 10 had prior chemotherapy. Conclusions: CPT–11 and 5–FU/leucovorin, as constituents of this novel mechanism-based schedule, have promising activity in patients who have received prior chemotherapy. The recommended phase II/III starting doses are CPT–11 275 mg/m2 over 90 min on day 1, and 5–FU 400 mg/m2 plus leucovorin 20 mg/m2 on days 2–5 every 21 days. This combination can be administered safely to this schedule if there is strict adherence to the 90 min infusion time for both CPT–11 and 5–FU.

Original languageEnglish (US)
Pages (from-to)1674-1680
Number of pages7
JournalAnnals of Oncology
Issue number10
StatePublished - Oct 2002


  • 5-Fluorouracil
  • Irinotecan
  • Leucovorin
  • Phase I

ASJC Scopus subject areas

  • Hematology
  • Oncology


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