Phase II study of a triplet regimen in advanced colorectal cancer using methotrexate, oxaliplatin and 5-fluorouracil

• Published in: British journal of cancer 2004-10, Vol.91 (8), p.1428-1433
• Main Authors: Guglielmi, A, Barni, S, Zaniboni, A, Pella, N, Belvedere, O, Beretta, G D, Grossi, F, Frontini, L, Puglisi, F, Labianca, R, Sobrero, A
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; clinical; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - pathology; Disease-Free Survival; Drug Resistance; Epidemiology; Feasibility Studies; Female; Fluorouracil - administration & dosage; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Liver Neoplasms - drug therapy; Liver Neoplasms - secondary; Lung Neoplasms - drug therapy; Lung Neoplasms - secondary; Male; Medical sciences; Methotrexate - administration & dosage; Middle Aged; Molecular Medicine; Oncology; Organoplatinum Compounds - administration & dosage; Oxaliplatin; Peritoneal Neoplasms - drug therapy; Peritoneal Neoplasms - secondary; Short Communication; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Treatment Outcome; Tumors
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6602176

Building upon the concept of schedule-specific biochemical modulation of 5-fluorouracil (FU), which alternates bolus and continuous infusion (CI) FU, we have incorporated oxaliplatin (l-OHP) following the bolus part of the regimen to explore the activity of this new combination. Patients with advanced, untreated, measurable colorectal cancer received sequential methotrexate (MTX) (days 1 and 15) → l-OHP+FU (days 2 and 16) (200, 85 and 600 mg m −2 , respectively) followed by 3 weeks of CI FU (200 mg m −2  day −1 ) given from day 29 to 50, modulated by weekly leucovorin (LV) (20 mg m −2 ). After 1 week of rest, the second cycle was started. The treatment was continued until progression or patient's refusal. According to the intention-to-treat analysis on all 46 patients accrued, the response rate was 42% (95% CL=28–55%), with three complete responses and 16 partial responses. The median overall survival was 15.9 months and the median progression-free survival 6.9 months. Toxicity was very mild, with the bolus part of the regimen more toxic than the infusional part (24 vs 7% of grade III–IV, respectively). This new combination of MTX → l-OHP−FU followed by FU CI is well tolerated, feasible and produces activity results similar to other more simple, but more toxic, regimens. Pros and cons of the different fluoropyrimidines–l-OHP combinations are discussed.