Oxaliplatin with high-dose leucovorin and 5-fluorouracil 48-hour continuous infusion in pretreated metastatic colorectal cancer

• Published in: European journal of cancer (1990) 1997-02, Vol.33 (2), p.214-219
• Main Authors: de Gramont, A., Vignoud, J., Tournigand, C., Louvet, C., André, T., Varette, C., Raymond, E., Moreau, S., Le Bail, N., Krulik, M.
• Format: Article
• Language: English
• Subjects: 5-FU infusion; Adenocarcinoma - drug therapy; Adenocarcinoma - secondary; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Colonic Neoplasms - pathology; colorectal cancer; Drug Administration Schedule; Female; Fluorouracil - administration & dosage; folinic acid (leucovorin); Gastroenterology. Liver. Pancreas. Abdomen; Humans; Infusions, Intravenous; Leucovorin - administration & dosage; Male; Medical sciences; Middle Aged; Organoplatinum Compounds - administration & dosage; Other diseases. Semiology; Oxaliplatin; Rectal Neoplasms - pathology; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Survival Rate; Treatment Outcome
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/S0959-8049(96)00370-X

Oxaliplatin has shown in vivo cytotoxic activity against colorectal cell lines. Preliminary studies suggest potentiation of fluorouracil (5-FU). To assess this issue, we performed a phase II study in pretreated patients with advanced colorectal cancer (CRC) resistant to leucovorin and 5-FU. The regimen (FOLFOX2) consisted of oxaliplatin 100 mg/m 2 as a 2-h infusion on day 1; leucovorin 500 mg/m 2 as a 2-h infusion, followed by 5-FU 24-h infusion 1.5–2 g/m 2 for two consecutive days every 2 weeks. The initial 5-FU dose was 1.5 g/m 2 for two cycles and increased to 2 g/m 2 in case of no toxicity > grade 2. 46 patients were treated, all with disease progression on leucovorin and 5-FU therapy for metastatic disease, or relapse less than 6 months after the end of adjuvant therapy. One complete response (CR) and 20 partial responses (PRs) were observed for an overall response rate of 46%. 22 patients had prior documented progression while receiving the same schedule of leucovorin and 5-FU as the one used in the FOLFOX2 regimen, and among them, 10 had PRs (45%). From the start of FOLFOX2, median progression-free survival was 7 months and median survival 17 months. WHO toxicity ⩾ grade 3 per patient was: peripheral neuropathy 9%, nausea 4%, diarrhoea 9%, mucositis 13%, neutropenia 39%, thrombocytopenia 11%, alopecia 9%, and allergy 2%. Overall, 21 patients (46%) experienced grade 3–4 toxicity. This combination of leucovorin, 5-FU and oxaliplatin achieves a high response rate in pretreated patients with CRC resistant to leucovorin and 5-FU. Limiting toxicities are neutropenia and peripheral neuropathy.