Primary therapy of metastatic prostate cancer (stage D2, pT3N1M1, GII/III) consists either of orchiectomy/1.0 g/m2 diethylstilbestrol-diphosphate (DESP) for 10 days or of antiandrogens plus luteinizing hormone releasing hormone analogues or of primary cytotoxic compounds – all resulting in an average response rate of 60–80% for 2–5 years. Tumor progression diagnosed by increase of PAP, PSA, bone scan, and/or urinary obstruction can again be treated by 1 g/m2 DESP, improving the performance status (Karnofsky index) by 50–70%. The high incidence (about 40%) of toxicity of estrogens (cardiovascular, edema, gastrointestinal) has caused a distinct decline in the use of DESP in the primary and secondary therapy. Our pharmacokinetic studies considered DESP a prodrug with subsequent bioactive metabolites, being modulated by liver/kidney and the enterohepatic system. On the basis of this clinical research work, two pilot studies have been performed: (1) DESP 1 g/m2 plus Farmorubicin 40 mg/m2/week on an outpatient basis. Three of 5 patients survived longer than 6 months with their hormone (Estracyt) resistant prostate carcinoma, having a low pain status (Karnofsky index > 30%). Side effects were tolerable. In another trial the patients were treated with 3 g/day ifosfamide (short-term infusion) plus adequate Uromitexane for 5 days and 1.0 g/m2 DESP for 10 days. The Karnofsky index was significantly improved with moderate toxicity (gastrointestinal tract). Studies 1 and, probably, 2 show that various multimodal therapies produce similar effects in progressive prostate cancer, however, with different toxicities. The bioactivation of the metabolites of DESP after preinfusion with cytotoxic compounds such as Farmorubicin or ifosfamide is presently investigated.

Keywords:
Prostate cancer, Therapies, Progression rate, Hormonal, nonhormonal agents
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© 1988 S. Karger AG, Basel
1988
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