Health and Prostate

In recent weeks, the FDA has approved two drugs for prostate cancer: Hoechst’s antiandrogen nilutamide (Nilandron) for metastatic disease and Immunex’ antineoplastic mitoxantrone (Novantrone) for hormone-resistant disease. Neither drug offers a cure for prostate cancer, but both delay disease progression and provide relief of bone pain.

Nilutamide

Nilutamide (Nilandron) is indicated for add-on therapy following surgical or chemical castration. The drug promotes disease regression, prolongs survival, and decreases bone pain. In one double-blind, randomized multicenter study comparing 225 castrated patients who received nilutamide and 232 castrated patients who received placebo, patients in the nilutamide group showed a longer progression-free survival (21.2 months in the nilutamide group versus 14.7 months in the placebo group), a longer median overall survival (27.3 months versus 23.6 months), and significant improvements in bone pain (54% versus 37%). Side effects, experienced by 86% of nilutamide patients, included hot flashes (28% incidence in treated patients and 22% in placebo patients) and transient night blindness (13% in treated patients and 1% in placebo patients). Less frequent side effects seen in clinical studies were nausea, constipation, and dizziness. Two serious side effects were pulmonary toxicity (2% incidence of interstitial pneumonitis) and hepatotoxicity (1% incidence of hepatitis or marked increases in liver enzymes).

The recommended dosage of nilutamide is six 50-mg tablets once daily for 30 days, followed by three 50 mg tablets once daily, with therapy beginning the same day or the day after surgical castration.

Mitoxantrone

Mitoxantrone (Novantrone) is indicated for hormone-resistant prostate cancer when given in combination with corticosteroids. Available for about 10 years for the treatment of acute non-lymphocytic leukemia, mitoxantrone is also under investigation for metastatic breast cancer and non-Hodgkin’s lymphoma. The drug was approved for prostate cancer on the strength of one open-label Canadian study showing that mitoxantrone plus prednisone significantly reduced bone pain in patients who had failed hormone therapy. The unblinded Canadian study involved 161 patients whose cancer had progressed despite castration and antiandrogen therapy (estrogen, luteinizing-hormone-releasing hormone agonists, cyproterone acetate, or flutamide). Patients were randomized to mitoxantrone 12 mg/m2 IV every three weeks plus 5 mg oral prednisone twice daily, or to prednisone alone. Patients who did not respond to prednisone alone were crossed over to mitoxantrone plus prednisone.

Overall, 38% of patients in the mitoxantrone plus prednisone group reported pain relief (or reduction in analgesic use) compared with 12% of patients on prednisone alone. The duration of pain relief was 33 weeks for the combination and eight weeks for prednisone alone. Also, mitoxantrone delayed progression of the disease (time to progression was 24 weeks compared to 10 weeks for prednisone alone) and reduced prostate specific antigen levels (PSA dropped 75% or more in 27% of patients receiving mitoxantrone compared with 5% of patients on prednisone alone). The most common side effects were nausea, hair loss, fatigue, weight loss and infection, and the most serious side effects were left ventricular dysfunction and myelosuppression. Despite the side effects, mitoxantrone therapy was associated with improvements in the quality of life, both physical and functional.