In a study of 127 patients with advanced measurable pancreatic cancer, objective response rates of 2% (melphalan), 10% (5-FU and methyl-CCNU), and 7% (5-FU, methyl-CCNU, and streptozocin) were achieved. No responses occurred in the 28 patients treated with VP-16-213 who had already received prior chemotherapy. Toxicity was greater for the two- and three-drug combinations than for melphalan. There was no difference in survival following use of the three treatment regimens. Further studies are needed to develop effective chemotherapy for patients with cancer of the pancreas.