Patients with metastatic colorectal carcinoma who have failed 5-fluorouracil-based chemotherapy have no effective second-line treatment available. Recent studies demonstrating clinical synergy between cisplatin and etoposide, and others exploring the efficacy of etoposide regimens utilizing chronic oral administration, suggested the utility of a new regimen incorporating these elements to treat refractory colorectal carcinoma. Fourteen patients were treated with weekly cisplatin and daily oral etoposide for 21 days in cycles of 28-35 days. Toxicity was significant, both hematologic and gastrointestinal in these pretreated patients. There were no objective responses, and median survival was 9.5 months. Weekly cisplatin and daily oral etoposide are poorly tolerated and ineffective in the treatment of refractory colorectal carcinoma. Further studies are needed to discover effective therapy for this disease.