The effects of cyclophosphamide, ketoconazole, aclacinomycin-A, methotrexate, and scheduled methotrexate-5-fluorouracil combination chemotherapy on the transplantable R-3327 prostatic adenocarcinoma in the F1 hybrid male rat

Abstract

Male F₁ hybrid rats bearing the R-3327 transplantable prostatic adenocarcinoma demonstrating similar growth patterns within the original sample of animals were carefully separated into control and treatment groups. This assured treatment of tumors with similar cell kinetics within each group. In the first study, two separate drug protocols were investigated by intraperitoneal injection, namely cyclophosphamide (100 mg/kg) once every 4 weeks for 8 weeks and scheduled methotrexate (7.5 mg/kg) followed in 90 minutes by 5-fluorouracil (50 mg/kg) once each week for 8 weeks. Excellent suppression of tumor growth was obtained with each treatment protocol. Both were significant at the 0.01 level. In the second study, methotrexate (100 mg/kg) intraperitoneally once each week for 6 weeks, aclacinomycin-A intraperitoneally once each week for 4 weeks, and ketoconazole (60 mg/kg) via gavage 5 times a week for 6 weeks were administered to the animals in each respective group. Aclacinomycin-A and ketoconazole showed significant suppression of tumor growth at the 0.01 and 0.05 levels, respectively. Methotrexate suppressed tumor growth, but did not reach levels of significance over the duration of the study (0.2 < P < 0.3).