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Trimetrexate in advanced hormone-refractory prostate cancer. An ECOG phase II trial
Abstract:
The antitumor activity and toxicity of trimetrexate (TMTX) was evaluated in measurable, hormone-refractory, advanced prostate cancer patients. Patients were required to have an ECOG performance status < 3, bidimensionally measurable disease, serum creatinine < or = 1.5 mg/dL, normal bone marrow function, and adequate hepatic function. Prior non-hormonal systemic therapy, active infection, third space effusions were exclusion criteria. TMTX 12 mg/m2 daily for five days (8 mg/m2 for patients with any prior radiation therapy or age > or = 75 years) was administered every 3 weeks. There were no responses in the 18 eligible patients. Median time to treatment failure and median survival were 6 and 20 weeks, respectively. Myelosuppression was the most frequent toxicity observed and was mild to severe in all but 4 patients. Two patients whom experienced life-threatening reversible leukopenia and grade 4 thrombocytopenia developed in 2 further patients. Non-hematologic toxicity was also reversible and was mild to severe. TMTX at this dose and schedule is inactive in advanced, hormone-refractory prostate cancer.
Insights
Trimetrexate (TMTX) showed no antitumor activity in advanced prostate cancer patients. The drug caused significant myelosuppression and other toxicities, indicating it is inactive at this dose and schedule.
Area of Science:
- Oncology
- Pharmacology
Background:
- Advanced prostate cancer, particularly hormone-refractory, presents significant treatment challenges.
- Evaluating novel chemotherapeutic agents is crucial for improving patient outcomes.
Purpose of the Study:
- To assess the antitumor activity and toxicity of trimetrexate (TMTX) in patients with advanced, hormone-refractory prostate cancer.
- To determine the safety profile and efficacy of TMTX in this patient population.
Main Methods:
- A clinical trial was conducted on 18 eligible patients with measurable, hormone-refractory, advanced prostate cancer.
- Patients received trimetrexate (TMTX) at a dose of 12 mg/m2 daily for five days every 3 weeks (or 8 mg/m2 for specific subgroups).
- Eligibility criteria included ECOG performance status < 3, measurable disease, and adequate organ function.
Main Results:
- No objective tumor responses were observed in any of the 18 eligible patients.
- The median time to treatment failure was 6 weeks, and the median survival was 20 weeks.
- Myelosuppression was the most common toxicity, observed in all but 4 patients, with some experiencing severe leukopenia and thrombocytopenia.
Conclusions:
- Trimetrexate (TMTX) demonstrated no antitumor activity in advanced, hormone-refractory prostate cancer at the tested dose and schedule.
- The observed toxicities, primarily myelosuppression, were significant and limit its therapeutic potential in this setting.