Improved Survival in Patients With Advanced Colorectal Carcinoma Failing 5-Fluorouracil Who Received Irinotecan Hydrochloride and Have High Intratumor C-fos Expression

This study determines the prognostic role of c-fos protein expression in patients with colon cancer who previously failed therapy with 5-fluorouracil (5-FU). Patients with advanced colorectal who were refractory to 5-FU therapy received irinotecan (CPT-11) by a 90-minute intravenous infusion at a dose of 125 mg/m2 weekly for four weeks followed by a 2-week rest period were eligible for oncogene assessment. C-fos protein expression was evaluated using archival formalin-fixed, paraffin-embedded tumor tissue, and an automated immunoperoxidase histochemical technique. Thirty-five patients were found to have > 25% positive c-fos activity. Nine patients had no detectable c-fos expression. Characteristics of patient subgroups were not different, however, the median survival of patients with elevated c-fos expression from the time of treatment with CPT-11 was 436 days, whereas patients with no detectable c-fos expression had a median survival of 365 days (p = 0.045). C-fos exhibits a casual role in the initiation of apoptosis and is implicated in differentiation and proliferation. It has been shown to correlate with poor survival in breast cancer, but improved survival in patients with astrocytic glioma. In this analysis, there is a suggestion that elevated c-fos expression is a good prognostic marker for patients with refractory colorectal carcinoma.