A PHASE-II STUDY OF CONTINUOUS-INFUSION 5-FLUOROURACIL IN ADVANCED HORMONE-REFRACTORY PROSTATE-CANCER - AN ILLINOIS CANCER CENTER STUDY

Background. 5-Fluorouracil (5-FU) has been previously associated with therapeutic benefit in hormone refractory prostate cancer. However, no previous study has administered 5-FU as a prolonged continuous infusion, which may be the optimal schedule for this cell-cycle specific agent. Methods. Therefore, 25 patients were treated with 5-FU administered as a continuous intravenous infusion at a dose of 1000 mg/m2/day for 5 days every 28 days. Eligibility required disease defined by bidimensionally measurable lesions or evaluable lesions on bone scan or radiograph with elevated serum levels of prostate-specific antigen (PSA), no severe cytopenias, and an Eastern Cooperative Oncology Group performance status less than 3. Prior chemotherapy was not allowed. Dose modifications were specified for mucositis and hematologic toxicity. Results. Eighteen of 22 patients were evaluable for response and toxicity, whereas 4 were evaluable for toxicity alone. Toxicity was significant using this dose and schedule and included episodes of sudden death (one patient), paroxysmal supraventricular tachycardia (one patient), and congestive heart failure (one patient). Other Grade 3 toxicities included stomatitis (two patients) and diarrhea (one patient). Significant myelosuppression did not occur. Objective responses were not observed, but 12 patients experienced stable disease with a median duration of 4 months. Conclusions. Infusional 5-FU can not be recommended for the treatment of advanced hormone refractory prostate cancer.