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Triplet Combination With Irinotecan Plus Oxaliplatin Plus Continuous-Infusion Fluorouracil and Leucovorin as First-Line Treatment in Metastatic Colorectal Cancer: A Multicenter Phase II Trial

From the Department of Medical Oncology and Department of Radiology, School of Medicine, University General Hospital of Heraklion, Crete; and Department of Medical Oncology, General Hospital of Larisa, Larisa, Greece.

Address reprint requests to Vassilis Georgoulias MD, PhD, Department of Medical Oncology, University General Hospital of Heraklion, P.O. Box 1352, Heraklion 71110, Crete, Greece; e-mail: georgsec{at}med.uoc.gr

PURPOSE: To evaluate the efficacy and tolerance of irinotecan (CPT-11) in combination with oxaliplatin (L-OHP) plus fluorouracil (5-FU)/leucovorin (LV) (de Gramont regimen) as first-line treatment of metastatic colorectal cancer (MCC).

PATIENTS AND METHODS: Thirty-one patients with MCC who had not received prior therapy for metastatic disease were enrolled. Their median age was 60 years; performance status (World Health Organization) was 0 in 12, 1 in 14, and 2 in five patients; 19 patients (61%) had prior surgery, and 14 (45%) had adjuvant chemotherapy. CPT-11 was administered on day 1 at 150 mg/m² as a 90-minute intravenous (IV) infusion; L-OHP was administered on day 2 at 65 mg/m² as a 2-hour IV infusion; and on days 2 and 3, LV 200 mg/m² preceded 5-FU administration of 400 mg/m²/d initial IV bolus dose followed by 600 mg/m²/d 22-hour IV continuous infusion. The regimen was repeated every 2 weeks.

RESULTS: All patients were assessable for toxicity and 30 for response to treatment. Complete response was achieved in two patients (6.5%) and partial response in 16 (51.6%) (overall response rate, 58.1%; 95% confidence interval, 40.7% to 75.4%); eight patients (25.8%) had stable disease, and five (16.1%) had disease progression. The median duration of response was 9 months, and the median time to disease progression was 13 months. Neutropenia grade 3 to 4 occurred in 14 patients (45%) and febrile neutropenia in two (6%). Diarrhea grade 3 to 4 was observed in 10 patients (32%), neurotoxicity grade 3 to 4 in three (9%), and asthenia grade 3 in two (10%). No treatment-related death has occurred.

CONCLUSION: The triplet combination of 5-FU/LV + CPT-11 + L-OHP is a highly active regimen with manageable toxicity as front-line treatment in MCC.

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