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

Abstract

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 mg/m(2) (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/m(2) over 90 min on day 1, and 5-FU 400 mg/m(2) plus leucovorin 20 mg/m(2) 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.

• Authors: 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
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 13 Issue 10 Pg. 1674-80 (Oct 2002) ISSN: 0923-7534 [Print] England
• PMID: 12377659 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Irinotecan
• Leucovorin
• Fluorouracil
• Camptothecin

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Camptothecin (administration & dosage, analogs & derivatives)
• Diarrhea (chemically induced)
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Fatigue (chemically induced)
• Female
• Fluorouracil (administration & dosage)
• Humans
• Infusions, Intravenous
• Injections, Intravenous
• Irinotecan
• Leucovorin (administration & dosage)
• Male
• Middle Aged
• Neoplasms (drug therapy)
• Neutropenia (chemically induced)