Palliative chemotherapy can add to the duration and quality of life in patients with advanced pancreatic and biliary cancer, albeit in a limited way. Between March 1995 and October 1997, 31 symptomatic patients were treated with etoposide in a phase II trial. Measurements of objective and subjective responses were performed, the latter by the treating physician and with the method of clinical benefit response (CBR). Quality of life was evaluated with the EORTC QLQ-C30 questionnaire. A partial response was seen in 2 (6%) patients. Subjective responses/quality of life gains were seen in 6 (19%), 7 (23%) and 9 (29%) patients, respectively, with the different methods. Median survival was 4.5 months. WHO grade 3 and 4 toxicity, alopecia excluded, was seen in 20% of the patients. The clinical activity of etoposide is limited, and in the same low range as other drugs in these diseases.