TRIMETREXATE IN ADVANCED HORMONE-REFRACTORY PROSTATE-CANCER - AN ECOGPHASE-II TRIAL

The antitumor activity and toxicity of trimetrexate (TMTX) was evaluat ed in measurable, hormone-refractory, advanced prostate cancer patient s. Patients were required to have an ECOG performance status < 3, bidi mensionally measurable disease, serum creatinine less than or equal to 1.5 mg/dL, normal bone marrow function, and adequate hepatic function . Prior non-hormonal systemic therapy, active infection, third space e ffusions were exclusion criteria. TMTX 12 mg/m(2) daily for five days (8 mg/m(2) for patients with any prior radiation therapy or age greate r than or equal to 75 years) was administered every 3 weeks. There wer e no responses in the 18 eligible patients. Median time to treatment f ailure and median survival were 6 and 20 weeks, respectively. Myelosup pression was the most frequent toxicity observed and was mild to sever e in all but 4 patients. Two patients whom experienced life-threatenin g reversible leukopenia and grade 4 thrombocytopenia developed in 2 fu rther patients. Non-hematologic toxicity was also reversible and was m ild to severe. TMTX at this dose and schedule is inactive in advanced, hormone-refractory prostate cancer.