Phase II trial of oral piritrexim in advanced, previously treated transitional cell cancer of bladder

Oral piritrexim (PTX), a second generation antimetabolite, has been shown to be an active agent against methotrexate refractory transitional cell cancer (TCC) of the bladder in phase I trials. We conducted a phase II trial of this drug in patients with TCC of the bladder who failed a first line chemotherapy regimen. Methods: Oral PTX was started at the dose of 25 mg three times per day for 5 days weekly for 3 weeks followed by one week of rest. If this was tolerated the dose was increased to 50 mg three times a day. Patients were monitored for response rate and toxicity. Results: Seventeen patients were entered into the trial. Two patients did not complete the required 2 courses of treatment to be evaluable. There were 13 evaluable patients. Among the 13 no one achieved a complete response (CR), however, there were 3 partial responses (PRs=RR: 23%) and 5 stable diseases (SDs). The responses lasted 2, 8 and 14 months. The major dose-limiting toxicity was myelosuppression. Two patients died on treatment. One death was due to neutropenic fever and the cause of death in the second patient is thought to be a cerebral vascular accident (CVA). Conclusion: PTX is an active drug in the treatment of TCC of the bladder. Bone marrow suppression is the most common dose-limiting toxicity. In view of the observed responses and toxicities in this study and other studies, we suggest that the role of PTX be further investigated in the following clinical settings: 1. Palliative initial treatment in patients with TCC of the bladder who are not candidates for more aggressive chemotherapy. 2. As first line chemotherapy in combination with other active drugs.