Biweekly chemotherapy with oxaliplatin, irinotecan, infusional Fluorouracil, and leucovorin: a pilot study in patients with metastatic colorectal cancer.

Abstract

PURPOSE:

To determine the feasibility, recommended doses, plasma pharmacokinetics, and antitumor activity of a biweekly chemotherapy regimen with oxaliplatin (L-OHP), irinotecan (CPT-11), infusional fluorouracil (5-FU), and leucovorin (LV) in metastatic colorectal cancer patients.

PATIENTS AND METHODS:

Patients received CPT-11 followed by L-OHP and LV 200 mg/m(2) and followed by 5-FU 3,800 mg/m(2) as a 48-hour infusion, repeated every 2 weeks. In the first part of the study, an escalation of CPT-11 dose and/or a decrease of the L-OHP dose were planned. Once the recommended doses of CPT-11 and L-OHP were determined, all subsequent patients were treated at the recommended doses.

RESULTS:

Forty-two patients entered the study. CPT-11 175 mg/m(2) and L-OHP 100 mg/m(2) in combination with LV 200 mg/m(2) and 5-FU 3,800 mg/m(2) could be administered with acceptable toxicities; 39 patients were treated at these dose levels. The pharmacokinetics parameters of the agents used and their metabolites did not seem to be influenced by the concomitant use of the other drugs. The most relevant toxicities were diarrhea and neutropenia, with 14% of patients experiencing one episode of febrile neutropenia. In five patients (11.9%) a complete and in 25 (59.5%) a partial response was demonstrated, for an objective response rate of 71.4% (95% confidence interval, 47% to 83%). In 11 patients (26%), a surgical resection of residual disease could be performed. Median progression-free and overall survival times were 10.4 and 26.5 months, respectively.

CONCLUSION:

This biweekly regimen is feasible and has acceptable and manageable toxicities and no apparent relevant pharmacokinetics interactions. This combination is associated with a promising antitumor activity, time to progression, and survival. A phase III randomized trial in Italy planned by the Gruppo Oncologico Nord Ovest has just started.

• Authors: Alfredo Falcone, Gianluca Masi, Giacomo Allegrini, Romano Danesi, Elisabetta Pfanner, Isa Maura Brunetti, Antonello Di Paolo, Samanta Cupini, Mario Del Tacca, Pierfranco Conte
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 20 Issue 19 Pg. 4006-14 (Oct 01 2002) ISSN: 0732-183X [Print] United States
• PMID: 12351598 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article)

Chemical References

• Organoplatinum Compounds
• Oxaliplatin
• Irinotecan
• Leucovorin
• Fluorouracil
• Camptothecin

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects, pharmacokinetics)
• Camptothecin (administration & dosage, adverse effects, analogs & derivatives, pharmacokinetics)
• Colorectal Neoplasms (drug therapy, pathology)
• Female
• Fluorouracil (administration & dosage, adverse effects, pharmacokinetics)
• Humans
• Infusions, Intravenous
• Irinotecan
• Leucovorin (administration & dosage, adverse effects, pharmacokinetics)
• Male
• Middle Aged
• Neoplasm Metastasis
• Organoplatinum Compounds (administration & dosage, adverse effects, pharmacokinetics)
• Oxaliplatin
• Pilot Projects
• Survival Analysis
• Treatment Outcome