Objective: This phase II study was designed to evaluate the efficacy and toxicity of 3-h interval sequential methotrexate (MTX) and 5-fluorouracil (5-FU) with leucovorin (LV) rescue in the treatment of patients with metastatic colorectal cancer.
Methods: Forty-two patients with histologically confirmed metastatic colorectal cancer and at least one two-dimensionally measurable lesion, aged 30-74 years old, with performance status < or =2 and no or one prior chemotherapy were selected. Patients received sequential MTX 100 mg/m2 by bolus injection and 5-FU 600 mg/m2 at 3 h followed by LV rescue initiated after 24 h (15 mg per body every 6 h for six doses). The treatment was repeated every week or every 2 weeks until disease progression. All patients were treated as out-patients unless complications arose.
Results: All 42 patients entered in this study were assessable both for response and toxicity. Fifteen patients achieved objective responses (one complete and 14 partial), for an overall response rate of 36% (95% CI: 11-51%). Response rates in pretreated patients and patients with naive chemotherapy were 27 and 42%, respectively. Sixteen patients had stable disease and 11 progressed with therapy. The median survival for all patients was 378 days. The hematological toxicity was mild with no grade 3/4 leukopenia. The major non-hematological toxicity was diarrhea (one grade 4, four grade 3).
Conclusions: This 3-h interval sequential MTX and 5-FU with LV rescue is an active regimen in patients with metastatic colorectal cancer. The treatment showed mild toxicity and was administered on an out-patient basis. The present findings suggest that this regimen warrants further investigation in patients with metastatic colorectal cancer.