Original Paper Oxaliplatin Added to the Simpli®ed Bimonthly Leucovorin and 5-Fluorouracil Regimen as Second-line Therapy for Metastatic Colorectal Cancer (FOLFOX6) F. Maindrault-Goebel, 1 C. Louvet, 1 T. Andre Â, 2 E. Carola, 3 J.P. Lotz, 2 J.L. Molitor, 1 M.L. Garcia, 1 V. Gilles-Amar, 1 V. Izrael, 2 M. Krulik 1 and A. de Gramont 1 on behalf of GERCOR 1 Service de Me Âdecine Interne-Oncologie, Ho à pital Saint-Antoine, 184, rue du Faubourg Saint-Antoine, 75571 Paris Cedex 12; 2 Service d'Oncologie Me Âdicale, Ho Ãpital Tenon, 4, rue de la Chine, 75970 Paris Cedex 20; and 3 Ho Ãpital de Senlis, Service de Me Âdecine 2, 60109 Senlis Cedex, France For patients resistant to leucovorin (LV) and 5-¯uorouracil (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% con®dence interval: 15±38), 27 (45%) had stable disease, 15 (25%) experienced disease progression and 2 (3%) had non-measurable disease. From the start of FOL- FOX6, 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 ®rst-line therapy. We are now investigating FOLFOX7, a regi- men with a higher oxaliplatin dose intensity and a lower 5-FU dose. # 1999 Elsevier Science Ltd. All rights reserved. Key words: oxaliplatin, 5-¯uorouracil, leucovorin, metastatic colorectal cancer Eur J Cancer, Vol. 35, No. 9, pp. 1338±1342, 1999 INTRODUCTION IN VITRO and in vivo preclinical studies on colorectal cancer have shown that oxaliplatin is active against colorectal cell lines and is synergistic with 5-¯uorouracil (5-FU) [1]. In phase II trials, oxaliplatin used as a single agent generated a 10% response rate with mild toxicity in patients whose dis- ease progressed whilst under treatment with ¯uoropyr- imidines [2]. Oxaliplatin has also been used in combination with leucovorin (LV) and 5-FU continuous infusion. The ®rst studies concerned a 5-day chronomodulated regimen [3]. The FOLFOX studies on patients whose cancers were resistant to LV±5-FU tested 48-h bimonthly regimens in combination with oxaliplatin at diVerent doses [4]. Figure 1 shows the diVerent FOLFOX regimens. The feasibility study (FOLFOX1) used the bimonthly regimen FOLFUHD with oxaliplatin (130 mg/m 2 ) every other cycle [5]. FOLFOX2 used FOLFUHD in conjunction with oxaliplatin (100 mg/ m 2 ) at every cycle [6]. FOLFOX3 combined FOLFUHD with oxaliplatin (85 mg/m 2 ) at every cycle [7, 8]. FOLFOX4 combined the bimonthly regimen LV5FU2 with oxaliplatin (85 mg/m 2 ) at every cycle [8]. The higher response rate with FOLFOX2 than FOLFOX3 and -4, respectively, 46% versus 18±23%, suggested that European Journal of Cancer, Vol. 35, No. 9, pp. 1338±1342, 1999 # 1999 Elsevier Science Ltd. All rights reserved. Pergamon Printed in Great Britain PII: S0959-8049(99)00149-5 0959-8049/99/$ - see front matter 1338 Correspondence to A. de Gramont, e-mail: aimery.de-gramont@sat. ap-hop-paris.fr Received 22 Jan. 1999; revised 18 May 1999; accepted 7 Jun. 1999.