前立腺癌(既治療例)に対する3ヵ月徐放性LH-RH agonist,TAP-144-SR(3M)(リュープリンSR注射用キット11.25)の臨床効果の検討

Abstract

前立腺癌103例を対象に, 24週で被験薬TAP-144-SR(3M)(TAP-144として11.25mg含有)2回投与(A群)と, 対照薬TAP-144-SR(1M)(TAP-144として3.75mg含有)6回投与(B群)に無作為割付した.血清中テストステロン濃度の去勢レベル維持率は両群とも100%であった.前立腺癌取り扱い規約中の「前立腺癌の非観血的治療効果判定基準」にしたがった総合効果の維持率は, A群80.4%, B群84.0%と有意差はなかった.A群のAUC1～12W実測値の平均値はB群の77.0%であった.安全性は両群とも特に問題はなかった.TAP-144-SR(3M)は, 長期にわたる前立腺癌治療に適した薬剤であることが示された

A randomized, multicenter, double-blind, parallel-group study was conducted in order to evaluate the hormonal kinetics, pharmacokinetics, efficacy and safety of TAP-144-SR (3M) a three-month sustained-release injectable preparation of leuprorelin acetate, a highly active luteinizing hormone-releasing hormone (LH-RH) derivative by comparing the treatment with two subcutaneous doses of the test medication TAP-144-SR (3M) and the treatment with six subcutaneous doses of the reference medication TAP-144-SR (1M), a 1-month sustained-release injectable preparation. Study participants were 103 patients with prostate cancer in whom a stable anti-tumor effect had been obtained with Leuplin Injection 3.75. The hormonal kinetics revealed that the proportion of the patients "maintaining the castration level of serum testosterone (maximum serum testosterone level during treatment below the castration level [100 ng/dl])" was 100% in both treatment groups. With regard to the efficacy, the proportions of the patients in whom the anti-tumor effects (> or = Stable) of the baseline treatment prior to the initiation of the treatment with the study medication were maintained during the study treatment period (6 months) were comparable; 84.0% with TAP-144-SR (1M) and 80.4% with TAP-144-SR (3M). On evaluation of the pharmacokinetics, the mean value of AUC1-12w of the serum TAP-144 concentration (including the metabolite M-I) for the treatment with TAP-144-SR (3M) was 77.0% that of the treatment with TAP-144-SR (1M). Adverse events were similar in the subjects on TAP-144-SR (3M) and in those on TAP-144-SR (1M). There existed no big differences in kind, incidence or time of occurrence of adverse events between two groups. TAP-144-SR (3M) showed no clinically relevant findings in particular. These results indicate that one dose of TAP-144-SR (3M) is comparable to three doses of the already approved Leuplin injection 3.75 in serum testosterone level-inhibitory effect, efficacy and safety. Hence, it is considered that TAP-144-SR (3M) is a drug suitable for treatment of prostate cancer over a prolonged period of time.