前立腺癌に対する徐放型LH-RH analogue, ICI 118630(Zoladex)の臨床効果

Abstract

前立腺癌患者12例に対し, LH-RH analogue, ICI 118630 (Zoladex(R))のDepot剤3.6 mg (1日平均溶出量120 μg)を4週ごとに3回皮下投与し, その安全性とホルモン動態への影響について検討を行い, あわせて抗腫瘍効果も評価した.臨床効果は, 対象病巣改善度でCR 1例, PR 6例, NC 3例, PD 2例で, 58.3%の改善がみられた.自覚症状総合改善度は8/10例に改善がみられた.内分泌効果では, 全例において本剤投与直後より血清ホルモンレベル(LH, FSH, testosterone)の上昇がみられたが, 2週目より有意に下降し, 本剤の薬理作用によると考えられるホルモン動態が観察され, 内分泌効果は100%を示した.なお, 12例の平均去勢時期は3.1±0.9週であった.副作用は女性化乳房1例, 高脂血症2例みられたが, いずれも軽微であり, 特別な処置を必要とせず試験を終了した.Zoladex(R)の血中濃度の推移から本在位の蓄積は認められなかった

The antitumor effect and safety and endocrinological effect of a depot formulation of luteinizing hormone-releasing hormone (LH-RH) analogue ICI 118630 (Zoladex) were studied. Each depot containing 3.6 mg of ICI 118630 (corresponding to the average daily release of 120 micrograms) was subcutaneously injected 3 times at 4 week intervals to 12 prostate cancer patients in total at 4 centers from August 1984 to March 1985. Of the 12 patients, 7 showed an objective clinical response (1 CR and 6 PR patients), 3 showed no change and the remaining 2 showed PD. Overall subjective improvement was obtained in 8 of 10 patients (80.0%). Serum hormone levels (LH, FSH, and testosterone) increased immediately after injection of depot and then significantly decreased during and after 2 weeks of treatment. These changes seen in 100% of the patients were attributable to the pharmacological action of the drug. Medical castration was attained in 3.1 +/- 0.9 weeks on average. Observed side effects included gynecomastia in 1 and hyperlipidemia in 2 patients which were all mild. The trial was continued in the patients who required no special medical treatment. Changes in blood Zoladex concentrations suggested no accumulation. These findings demonstrate the safety and useful endocrinological and antitumor effects of Zoladex in prostate cancer through its pharmacological action, that is, LH-RH agonistic action.