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Phase II trial of oral piritrexim in advanced, previously treated transitional cell cancer of bladder
1Department of Medicine, University of Wisconsin, Madison, USA.
Unlabelled:
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.
Insights
Oral piritrexim (PTX) shows activity in advanced bladder cancer. This phase II trial found PTX effective in patients with transitional cell cancer (TCC) who failed prior chemotherapy, with myelosuppression as a key toxicity.
Area of Science:
- Oncology
- Pharmacology
Background:
- Transitional cell cancer (TCC) of the bladder is a significant clinical challenge.
- Methotrexate-refractory TCC necessitates exploration of novel therapeutic agents.
- Piritrexim (PTX) is a second-generation antimetabolite with demonstrated activity in early trials.
Purpose of the Study:
- To evaluate the efficacy and toxicity of oral piritrexim (PTX) in patients with TCC of the bladder.
- To assess PTX as a second-line treatment option for patients who have not responded to first-line chemotherapy.
Main Methods:
- A phase II clinical trial was conducted.
- Patients received oral PTX at escalating doses (25 mg to 50 mg three times daily for 5 days weekly for 3 weeks).
- Response rate and toxicity, particularly myelosuppression, were closely monitored.
Main Results:
- Thirteen evaluable patients were assessed.
- A response rate of 23% (3 partial responses) was observed, with responses lasting up to 14 months.
- The primary dose-limiting toxicity was myelosuppression, with two treatment-related deaths.
Conclusions:
- Oral piritrexim (PTX) demonstrates activity in the treatment of TCC of the bladder.
- Myelosuppression is a significant dose-limiting toxicity requiring careful management.
- Further investigation of PTX is warranted in palliative settings or as part of combination chemotherapy.