Methyl-CCNU and methotrexate therapy in patients with advanced colorectal cancer after failure of 5-fluorouracil chemotherapy

Thirty-six patients with advanced colorectal cancer whose disease progressed during treatment with 5-fluorouracil (5-FU) chemotherapy were treated with methyl-CCNU and methotrexate. Five patients (14%) achieved a partial response (PR), three (8%) showed disease regression less than that required for a PR, and three (8%) showed evidence of stable disease. Twenty-five patients (69%) progressed on treatment. Tumor regression was seen only in patients with good performance status (ECOG 0.1). The median survival time of patients achieving a PR was 31 weeks. Those patients with stable disease or disease regression less than a PR had median survival times of 49 and 32 weeks, respectively. The comparable figure for those patients with disease progression was 17 weeks. Myelosuppression, principally in the form of leukopenia and thrombocytopenia, was common. Nausea and vomiting were universal with methyl-CCNU, and mucositis and diarrhea occurred commonly due to methotrexate. These results demonstrate the limited activity of chemotherapy in refractory colorectal cancer. They also reaffirm that poor pretreatment performance status should exclude patients from futile attempts at palliative therapy or phase II clinical trials, as these patients derive little or no benefit from them.