徐放型LH-RH analogue, ICI 118630 (Zoladex)による前立線癌内分泌療法

Abstract

前立腺癌患者90例に対し, ICI 118630 (Zoladex(R)) depot製剤(0.9 mg, 1.8 mg, 3.6 mg)を4週ごとに3回, 12週にわたって皮下投与し, 用量別に臨床効果, 安全性および内分泌動態への影響について検討した.臨床効果においては, 対象病巣改善度評価可能症例70例において, 0.9 mg群22例中14例, 1.8 mg群23例中11例3.6 mg群25例中17例の改善度が見られ, 自覚症状総合改善度も同様に72例中, 各々75.0%, 81.8%, 88.0%の改善がみられたが, 3群間に有意差はみられなかった.内分泌効果は, 評価可能症例75例中内分泌効果ありと認められたものは0.9 mg群25例中23例, で1.8 mg群, 3.6 mg群は各々全例に効果がみられたが, 3群間に有意差はみられなかった.Zoladex(R) depot剤投与による去勢効果は, 早くて2週でみられ, 全例平均去勢到達時期は3.5±1.7週であった.副作用は0.9 mg群26例中5例, 1.8 mg群29例中8例, 3.6 mg群30例中2例に認められたが, 3群間に有意差はみられなかった.臨床至適用量に関しては, 早期に去勢効果が得られることから3.6 mg投与が望ましい

To investigate the clinical efficacy, safety and endocrinology of ICI 118630 (Zoladex) depot formulation at 3 different dose levels (0.9, 1.8 and 3.6 mg), 90 patients were randomized to receive either one of the 3 doses from April, 1985 to March, 1986 in 28 centers. The depot preparation was injected subcutaneously every 4 weeks 3 times (for up to 12 weeks). Clinical efficacy was evaluated in terms of tumor response and overall subjective response. In 70 patients eligible for tumor response evaluation, 14 out of 22 (63.6%) in the 0.9 mg group, 11 out of 23 (47.8%) in the 1.8 mg group, and 17 out of 25 (68.0%) in the 3.6 mg group showed clinical improvement, that is, either complete response or partial response. In 72 eligible patients for overall subjective response evaluation, clinical subjective improvement was observed in 75.0, 81.8 and 88.0% of the patients in the 3 groups, respectively. There was no significant difference between the groups. As for endocrinology, there were 75 eligible patients. Endocrinological effect was observed in 23 out of 25 (92.0%) in the 0.9 mg group, 100% in both 1.8 mg and 3.6 mg groups. There was no significant difference between the groups. Castration was achieved by week 3.5 +/- 1.7 of therapy on average and by week 2 in the earliest case. There was no significant difference in incidence of side effects between the 3 groups: 5 out of 26 (19.2%) in the 0.9 mg group, 8 out of 29 (27.6%) in the 1.8 mg group, and 2 out of 30 (6.7%) in the 3.6 mg group. Flares presented as an increase in bone pain in 2 and as ureteric obstruction in 2 all in the 1.8 mg group but none in the other 2 dose groups. These flares disappeared on further treatment with Zoladex. These patients showed a clinical-response. The blood level of Zoladex was dose dependent, reaching its peak at week 2 of therapy in all 3 dose groups. There was no evidence of accumulation. Since these results demonstrate that 3.6 mg produces medical castration earlier, it may well be considered as an optimal dose in men.