Transperineal 125iodine implantation for treatment of clinically localized prostate cancer: 5-year tumor control and morbidity.

Purpose: To evaluate the efficacy and toxicity of transperineal 125I implants for clinically localized prostate cancer in elderly men in a community cancer setting.

Methods And Materials: From 1988 to 1993, 206 patients, median age 77 years, with localized (Stage T1 and T2), low-grade (Gleason score < or = 7) prostate cancer were treated using pre-planned 125I transperineal implants. Patients were followed for biochemical freedom from disease, overall survival, and treatment-associated morbidity.

Acrolein mercapturates: synthesis, characterization, and assessment of their role in the bladder toxicity of cyclophosphamide.

Acrolein is the metabolite of cyclophosphamide (CP) believed to be involved in the bladder toxicity associated with this anticancer drug. The mechanism by which this extremely reactive intermediate is delivered to the bladder is not known. Glutathione (GSH) readily conjugates with acrolein, and the acrolein mercapturate S-(3-hydroxypropyl)-N-acetylcysteine (3-hydroxy-PrMCA) has been found in the urine of animals and man given CP.

Murine strain differences in metabolism and bladder toxicity of cyclophosphamide.

Cyclophosphamide (CP) undergoes metabolic activation, generating phosphoramide mustard and acrolein which are believed to be responsible for the cytostatic and toxic effects, respectively. In this study, CP-induced bladder toxicity (hemorrhagic cystitis) was found to be significantly greater in the ICR than the C57BL/6N (C-57) strain of mice. Strain differences exist in the distribution of CP metabolites to the bladder, as evidenced by consistently higher levels of acrolein equivalents measured in the urine of the sensitive ICR strain.

Pharmacokinetics, metabolic activation, and lung toxicity of cyclophosphamide in C57/B16 and ICR mice.

A single intraperitoneal dose (200 mg/kg) of cyclophosphamide (CP) resulted in significantly less injury to the C57/B16 strain than to the ICR strain of mice. Maximal thymidine incorporation into total lung DNA, an indirect index of lung injury, and pulmonary hydroxyproline content, a marker of fibrosis, were 56 +/- 10% and 69 +/- 9 of ICR mice, respectively. Pharmacokinetics and metabolism of [side chain-3H]CP and [ring-14C]CP were assessed in vivo.