Phase I study of bicalutamide (Casodex), a nonsteroidal antiandrogen in patients with prostatic cancer

1)登録症例は16例で, 全例が適格例であった. 2)副作用は16例中8例に認められたが, 軽度で, 臨床上特に問題はなかった.乳房圧痛, 乳房腫脹等の副作用が50mg群で1例, 80mg群で3例及び100mg群で2例に認められた. 3)有効性に関しては, 各投与群の1例ないし2例において, PR以上の抗腫瘍効果が認められた.又, 排尿困難, 排尿痛, 夜間頻尿の改善がみられた. 4)血清中ホルモンでは, LH, FSH, testosterone及びestradiol濃度の上昇が認められた
A phase I study (open trial) of bicalutamide (Casodex), a non-steroidal antiandrogen, was conducted on 16 patients with prostatic cancer (stage C to D). The patients were given 10, 30, 50, 80 or 100 mg of bicalutamide orally daily for 12 weeks. Adverse reactions were observed in 8 out of 16 patients, but almost all were mild. Breast pain, gynecomastia and hot flushes were observed in 6 patients. Adverse reactions regarding liver function tests were observed in 3 patients. These were increased glutamic-oxalacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), alkaliphosphatase (AL-P) or gamma guanosine 5'-triphosphate (gamma-GTP). However, during or after the treatment period the elevated values were reversed to the pretreatment level. In terms of efficacy, anti-tumor effect was observed in 1 or 2 patients at each dose. Serum concentrations of luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone and estradiol increased during treatment. Plasma concentrations of the R (-) enantiomer, which has antiandrogenic activity, reached the steady state 6-8 weeks after the initiation of treatment; its apparent plasma elimination half-life observed following repeated administration was 8.4 +/- 1.1 days. In conclusion, bicalutamide (10-100 mg od) is considered to be tolerated well enough to be administered to patients with prostatic cancer and has shown evidence of anti-tumor effect.