前立腺癌に対する3ヵ月徐放型LH-RH agonist(Zoladex LA 10.8mg depot)の臨床効果の検討

Abstract

日本人前立腺癌患者40例(新鮮例20例, 切替例20例)を対象に, 10.8mgデポ1筒を単回皮下投与し, 有効性及び安全性を評価した.その結果, 薬力学的効果では, 新鮮例全例の血清テストステロン濃度は投与4週後迄に去勢域値以下へ抑制され, 12週後まで維持された.新鮮例の抗腫瘍効果を評価した結果, 投与12週後の奏効率は90.0%で, PSAの正常化率は75.0%であった.副作用は27例に見られ, ほてりが20.0%と最も高かった.10.8mgデポの投与結果を3.6mgデポの臨床成績と比較した結果, 有効性及び安全性は3.6mgデポと同様と考えられた.新鮮例で薬物血中濃度を測定した結果, 投与2時間後に最高血清中濃度に達し, 72時間後迄に速やかに減少した.前立腺癌患者に単回皮下投与することで, 有効性は12週間持続し, 3.6mgデポと同様の良好な忍容性を認めた

Pharmacodynamics (PD), anti-tumor effects, safety and pharmacokinetics of a 3-month formulation of goserelin (Zoladex (R)LA 10.8 mg depot: "10.8 mg depot") were investigated in a collaborative multicenter study. Study participants were 40 Japanese patients with prostate cancer comprising 20 untreated patients and 20 switch patients who had been receiving Zoladex(R) 3.6 mg depot for 3 months or longer. Serum testosterone levels, serum LH levels, prostate-specific antigen (PSA) levels and drug concentrations were measured until 12 weeks after a single subcutaneous dose of 10.8 mg depot. Anti-tumor effects were evaluated by means of changes in the tumor lesions and the PSA levels at 12 weeks. After administration to the untreated patients, 10.8 mg depot reduced serum testosterone to the castrate range within 4 weeks and the reduction was maintained for up to 12 weeks. In the switch patients, serum testosterone suppression that had been produced by previous treatment with Zoladex(R) 3.6 mg depot was maintained for up to 12 weeks following 10.8 mg depot administration. The anti-tumor effect at 12 weeks was 90.0% including partial response cases. The ratio of PSA normalization at 12 weeks was 75.0%. Fifty-seven adverse reactions were observed in 27 of the 40 patients (67.5%), but none were clinically significant. Although a disease flare presented as urinary retention in 1 of the untreated patients, all patients completed the study. Serum goserelin was detected up to 12 weeks after the administration of 10.8 mg depot. In conclusion a single dose of 10.8 mg depot showed a satisfactory PD-effect and brought about clinical efficacy persisting for at least 12 weeks and was well tolerated in patients with prostate cancer.