The objectives of this project are: (1) To investigate the activity of specific chemotherapeutic agents in advanced prostatic cancer, (2) to determine if sequential therapy with these agents is useful clinically, (3) to determine their therapeutic effectiveness against and in combination with current standard therapy, (4) to determine the predictive value of various in vitro evaluations of chemotherapeutic agents, (5) to investigate the advantage of chemotherapy in patients with stable stage D cancer of the prostate and (6) to determine the effectiveness of adjuvant chemotherapy in patients with stage B, C and D-1 cancer of the prostate. Thirteen separate protocols have been developed; six are currently active. Chemotherapeutic agents so far investigated are 5-Fluorouracil, Cytoxan, Estracyt, Streptozotocin, Procarbazine, DTIC, Leo 1031, Methyl-CCNU, Hydroxyurea and Vincristine. Additional agents under current investigation are Cis-platinum and Methotrexate. In our active protocols Cytoxan and Estracyt continue to be investigated because they have shown activity and benefit in our previous studies. All patients are treated for a minimum of twelve weeks at which time, if progression occurs, crossover to alternate agents is effected. If further progression occurs after crossover, patients are treated at the investigator's discretion, but all patients are followed to death. With patients evaluable to date in Protocols 100, 200, 300 and 400, patients treated with chemotherapy are approaching a statistically significant advantage over standard treatment. Patient entry into most of the remaining protocols is insufficient at this stage for statements about the efficacy of the chemotherapeutic agents utilized.