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.[42] 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.[43] 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.[45] 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).[45] 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.
