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Chemotherapy for hormone-refractory disease

Despite the effectiveness of initial hormonal therapy, metastatic prostate cancer is an incurable disease, with patients surviving a median of 9-12 months after the development of androgen insensitivity.

One very recent advance is the acceptance of PSA as a surrogate marker for response in hormone-refractory prostate cancer. Currently, a PSA decline of more than 50% from pre-treatment baseline, which persists for at least 4 weeks, is considered a partial response in clinical trials. Although not proven in a phase III setting, utilization of PSA levels has helped identify new, potentially active chemotherapy regimens for use in patients with advanced androgen-independent disease.

In this Section:

• Mitaxantrone plus prednisone
• Estramustine (Emcyt)

 

Mitaxantrone plus prednisone

The combination of Mitaxantrone (Novantrone) and prednisone has been approved for use in patients with hormone-refractory prostate cancer who are experiencing pain. Mitaxantrone (12 mg/ml IV) is administered every 3 weeks. Prednisone is given as a 10-mg oral daily dose. Toxicities of the combination include leukopenia and thinning of the hair.

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Estramustine (Emcyt)

Estramustine (Emcyt) is a chemo-hormonal agent that combines an estrogen molecule with a nitrogen mustard molecule. This unique agent binds to the nuclear matrix and to microtubule-associated proteins in the cytoplasm. In so doing, it synergizes the effects of the topoisomerase II inhibitor etoposide (acting within the nucleus) as well as the vinca alkyloids and taxanes (inhibiting microtubule formation in the cytoplasm). Several active regimens have been developed based on these properties; all of them have response rates of approximately 50%, as measured by PSA decline or a 50% decrease in the size of soft-tissue disease.

Estramustine (280 mg tid) and etoposide (50 mg bid ) are administered orally for 21 days and cycles are repeated every 8 days. Toxicities include temporary hair loss, leukopenia, anemia and nausea.

Estramustine (280 mg tid) and vinblastine ([Velban] 4-6 mg/m/wk IV) for 6 weeks every 8 weeks. Toxicities include nausea and leukopenia.

Estramustine (280 mg tid PO x 3d) and paclitaxel ([Taxol] 90 mg/m/IV on day 2) for 6 weeks every 8 weeks. Toxicities include leukopenia.

Estramustine (280 mg tid PO x 5d) and docetaxel ([Taxotere] 60 mg/m/IV on day 3) every 21 days. Toxicities include nausea, fatigue, and leukopenia.

 

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