Oxaliplatin added to the simplified bimonthly leucovorin and 5-fluorouracil regimen as second-line therapy for metastatic colorectal cancer (FOLFOX6)

• Published in: European journal of cancer (1990) Vol. 35; no. 9; pp. 1338 - 1342
• Main Authors: Maindrault-Goebel, F, Louvet, C, André, T, Carola, E, Lotz, J.P, Molitor, J.L, Garcia, M.L, Gilles-Amar, V, Izrael, V, Krulik, M, de Gramont, A
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Oxford Elsevier Ltd 01.09.1999; Elsevier
• Subjects: 5-fluorouracil; Biological and medical sciences; Gastroenterology. Liver. Pancreas. Abdomen; leucovorin; Medical sciences; metastatic colorectal cancer; oxaliplatin; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumors; 5-fluorouracil; oxaliplatin; metastatic colorectal cancer; leucovorin; Antineoplastic agent; Human; Treatment efficiency; Fluoropyrimidine derivatives; Calcium folinate; Metastasis; Malignant tumor; Colonic disease; Chemotherapy; Oxaliplatin; Digestive diseases; Intestinal disease; Pyrimidine derivatives; Colon; Therapeutic protocol; Fluorouracil; Platinum II Complexes
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/S0959-8049(99)00149-5

For patients resistant to leucovorin (LV) and 5-fluorouracil (5-FU), the addition of oxaliplatin (85 or 100 mg/m 2) to bimonthly LV–5-FU has given a response rate of 20–46%. The highest response rate has been observed with oxaliplatin 100 mg/m 2 (FOLFOX2). The present phase II study (FOLFOX6) infused oxaliplatin (100 mg/m 2) with LV (400 mg/m 2) as a 2-h infusion on day 1, followed by bolus 400 mg/m 2 and a 46-h infusion (2.4–3 g/m 2) of 5-FU, every 2 weeks. Among the 60 patients treated, 16 (27%) had partial responses (95% confidence interval: 15–38), 27 (45%) had stable disease, 15 (25%) experienced disease progression and 2 (3%) had non-measurable disease. From the start of FOLFOX6, median progression-free survival was 5.3 months and median survival 10.8 months. From the 448 cycles analysed, NCI-CTC grade 3–4 toxicities per patient were: peripheral neuropathy 16%, nausea 7%, diarrhoea 7%, mucositis 5%, neutropenia 24%, thrombocytopenia 2%. Overall 26 (46%) patients experienced grade 3–4 toxicities. Because of toxicity, only 36% of the patients received ≥90% of the scheduled oxaliplatin dose intensity. FOLFOX6 was active in pretreated patients resistant to LV–5-FU and is being investigated as first-line therapy. We are now investigating FOLFOX7, a regimen with a higher oxaliplatin dose intensity and a lower 5-FU dose.