Chemotherapeutic agents, including cyclophosphamide, doxorubicin, 5-fluorouracil, dacarbazine, cisplatin, estramustine, and streptozocin, alone or in combination, have produced disappointing overall response rates of approximately 30% (in those with mostly stable disease, with few complete or partial responses), with median survivals of 26 to 33 weeks. In one European trial of 29 patients with advanced, hormone-resistant prostate cancer, single-agent mitomycin C was associated with a total objective response rate of 59% and an actuarial median survival time of 10.8 months. The possibility of combination chemotherapy is a logical extensive of the finding of modest activity with several single agents.
Because of the poor survival results noted with chemotherapy in patients with hormone-resistant prostate cancer, the Southwest Oncology Group examined the role of combination hormone and chemotherapy. One hundred thirty-seven patients were randomized to receive hormonal therapy (DES or orchiectomy) followed by cyclophosphamide plus doxorubicin, at disease progression or as combined modality therapy was associated with a somewhat greater response rate (63% vs 48%, respectively; P = .059), there was no difference in median survival time (25.6 vs 22.0 months for the initial hormonal therapy group and the chemohormonal group, respectively). Thus, combined modality therapy cannot be recommended at this time.
Currently, new emerging therapies, such as abiraterone, enzalutamide, sipuleucel-T and cabazitaxel, will certainly change the way we treat hormone-resistant prostate cancer
. The development of prostate cancer after prolonged exposure to estrogens in transgender women raises questions in the "protective" role of castrate status in cancer pathogenesis.