Oxaliplatin activity against metastatic colorectal cancer. A phase II study of 5-day continuous venous infusion at circadian rhythm modulated rate

Francis Levi, Bruno Perpoint, Carlo Garufi, Christian Focan, Philippe Chollet, Petra Depres-Brummer, Rachid Zidani, Silvano Brienza, Moshe Itzhaki, Stefano Iacobelli, Francis Kunstlinger, Julio Gastiaburu, Jean Louis Misset

Research output: Contribution to journalArticlepeer-review

Abstract

Oxaliplatin (L-OHP) is a non-nephrotoxic third generation platinum complex with proven antitumoral activity and minimal haematological toxicity. Circadian scheduling has allowed significant increases in L-OHP dosage and dose intensity and decreases in its toxicities. This phase II trial has tested the antitumour activity of a 5-day circadian schedule of continuous venous infusion of L-OHP against metastatic colorectal cancer. Initial dose was 150 mg/m2/course. An intrapatient dose escalation scheme by 25 mg/m2/course was planned up to 200 mg/m2/course, according to toxicity criteria. The delivery rate of L-OHP was sinusoidally modulated along the 24-h time scale, and was highest at 1600 h. A programmable-in-time ambulatory pump was used, so that all patients could receive their treatment at home. 29 of 30 patients registered were eligible. 25 had failed previous chemotherapy. Three objective responses were observed (response rate: 10%), in patients progressive while on chemotherapy with 5-fluorouracil and folinic acid. Toxicity was moderate. Dose-limiting toxicities were diarrhoea and peripheral sensitive neuropathy. The latter adverse effect appeared to be cumulative. L-OHP, as delivered under this circadian schedule, exhibits clinical antitumour activity against metastatic colorectal cancer. These results, which await further confirmation, support the place of L-OHP in combination regimens including 5-fluorouracil.

Original languageEnglish
Pages (from-to)1280-1284
Number of pages5
JournalEuropean Journal of Cancer
Volume29
Issue number9
DOIs
Publication statusPublished - 1993

ASJC Scopus subject areas

  • Cancer Research
  • Hematology
  • Oncology

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