非ステロイド性抗アンドロゲン剤フルタミドの前立腺癌に対する治療効果第2相用量設定試験

Abstract

1)内分泌療法未治療の前立腺癌症例に対し, 375mg/日の用量で単独療法として使用しえる。この際, testosterone産生阻害療法に比し, 「生活の質」が保たれる。2)内分泌療法再燃例に対しても, ある程度その効果が期待できる。3)フルタミドと他の精巣性testosterone阻害剤との併用で, その併用効果が期待できる。4)また, LH-RHアナログの投与によるflare-up現象をフルタミドを併用することにより予防することが可能である

The phase II study of flutamide, a pure anti-androgen, was performed to estimate the clinical doses on 165 hormone untreated or treated patients with prostatic cancer. The hormone-untreated patients were given orally flutamide of 90, 375, 750 or 1, 125 mg/day in three divided doses daily for 12 weeks. Responses were not observed at the 90 mg/day dose except for improvement of clinical symptoms. However, an objective response rate of 48.8-46.7% was obtained at 375-1, 125 mg/day doses. In hormone-treated patients including cases refractory to the previous hormonal treatment, the objective response rates were 13.3 and 8.3% in 375 and 750 mg/day flutamide groups, respectively. Side effects such as gynecomastia, nausea, vomiting, diarrhea, and abnormal laboratory findings such as the elevation of hepatic transaminases were observed. The incidence increased dose-dependently. Determinations of serum hormone levels revealed an increase in testosterone levels by the use of flutamide. In conclusion 375 mg/day of flutamide is the optimal dose in monotherapy for hormone-untreated patients with prostatic cancer, where the quality of life can be maintained compared with therapies involving testosterone suppression. This dose is also expected to show some efficacy in cases refractory to hormone treatment.