mesna and Prostatic-Neoplasms

The combination of ifosfamide and mesna was evaluated in a phase II trial in the treatment of metastatic prostate cancer. Two separate groups of patients were to be evaluated: patients with no prior hormonal therapy and hormonally refractory patients. Patients were treated with ifosfamide 1.5 g/M2, and mesna at 30% of the ifosfamide dose was administered immediately before and 4 and 8 h after ifosfamide treatment. Both drugs were given i.v. daily for 5 days every 21 days. Response was assessed every 6 weeks. Of 29 eligible and evaluable patients with hormonally refractory disease, there were two partial responders for a response rate of 7% (95% confidence interval, of 0.1-23%). Of nine eligible patients with no prior hormone treatment, there was one partial response, for a response rate of 11% (95% confidence interval, 0.3-48%). Unfortunately, the target accrual goal for this arm of the study was never achieved. The most common toxicities were myelosuppression and neurologic toxicity. These drugs do not warrant further evaluation in the disease.

Topics: Adenocarcinoma; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Follow-Up Studies; Humans; Ifosfamide; Injections, Intravenous; Leukopenia; Male; Mesna; Neurologic Examination; Prostatic Neoplasms; Remission Induction; Survival Rate

Cyclophosphamide has been considered one of the reference drugs of chemotherapy in randomized trials in hormone-refractory prostate cancer by the National Prostatic Cancer Project (NPCP). Ifosfamide, another oxazaphosphorine agent, and an analog of cyclophosphamide, appears to be more active and less toxic in a broad spectrum of tumors. Fifteen patients with metastatic hormone-refractory prostate cancer were treated with continuous infusion of ifosfamide 2 g/m2 per day for 2 days, together with the uroepithelial protective agent Mesna 2.4 g/m2 per day for 2 days, both to be repeated every 3 weeks. All patients have failed on previous hormonal therapy and 7 patients had received previous chemotherapy. The median age was 66 years. Fourteen patients were evaluable; none of whom achieved an objective response. Four patients were stabilized and 10 had disease progression while on chemotherapy. Major toxicity included 2 reversible encephalopathy, 3 grade I reversible renal toxicity, and 1 hemorrhagic cystitis. We concluded that ifosfamide given in this schedule in this group of patients is not an active agent in prostate cancer.

Topics: Aged; Drug Administration Schedule; Humans; Ifosfamide; Male; Mesna; Middle Aged; Prostatic Neoplasms; Survival Analysis