Niijima T, Aso Y, Akaza H, Fujita K, Fuse H, Hosaka M, Isurugi K, Kamidono S, Katayama T, Kawabe K
Tokyo Seamen's Insurance Hospital.
Hinyokika Kiyo. 1990 Nov;36(11):1343-60.
TAP-144-SR is a sustained release formulation of an LH-RH agonist, leuprorelin acetate (TAP-144), that has been newly developed in Japan. As a phase I study, a single subcutaneous dose of TAP-144-SR was given to 15 patients with prostatic cancer to investigate the safety, endocrinological effects, and serum levels of the drug. The patients were divided into four groups according to the dosage levels of 1.88 mg, 3.75mg, 7.5 mg and 15 mg. No serious side effects were noted in any of the patients treated with any dose. No patients exhibited signs of a local reaction at the site of injection. In two patients transient exacerbation of clinical symptoms owing to "flare up" was observed. Serum testosterone levels decreased to the castration level (less than 1.0 ng/ml) in all of the patients, although the time required to attain the castration level tended to be longer in the patients receiving 1.88 mg. Serum TAP-144 levels increased on the first day and gradually decreased thereafter. In the groups of patients that received 3.75 mg or more of TAP-144-SR, TAP-144 was detected in the serum up to 4 weeks after administration. Based on the results of the phase I study, 3.75 mg and 7.5 mg of TAP-144-SR were selected as the doses for the phase II study. The phase II study was carried out as a multi-center open trial. Patients with stage B-D prostatic cancer received subcutaneously either 3.75 mg (3.75 mg group) or 7.5 mg (7.5 mg group) of TAP-144-SR once every 4 weeks for a total of 3 doses over a period of 12 weeks. TAP-144-SR 3.75 mg was administered to 51 patients and 7.5 mg to 50 patients. Both of these doses were adequate to suppress serum LH and FSH levels. Serum testosterone was decreased to the castration level within 22 days after the first dose, and this suppression was maintained throughout the treatment period. Clinical response rate (CR + PR) was 21% in the 3.75 mg group and 22-24% in the 7.5 mg group according to the Criteria for Evaluating the Direct Response to Chemotherapy in Solid Carcinomas and NPCP criteria. The response rate by the criteria of Japanese Prostatic Cancer Study Group was 51% in the 3.75 mg group and 62% in the 7.5 mg group. Adverse reactions were noted in 26% of patients in the 3.75 mg group and 34% in the 7.5 mg group.(ABSTRACT TRUNCATED AT 400 WORDS)
TAP - 144 - SR是促性腺激素释放激素（LH - RH）激动剂醋酸亮丙瑞林（TAP - 144）的缓释制剂，该制剂是在日本新开发的。作为一项I期研究，对15例前列腺癌患者皮下注射单剂量的TAP - 144 - SR，以研究该药物的安全性、内分泌学效应和血清水平。患者根据1.88毫克、3.75毫克、7.5毫克和15毫克的剂量水平分为四组。接受任何剂量治疗的患者均未出现严重副作用。没有患者在注射部位出现局部反应迹象。观察到2例患者因“flare up”出现临床症状短暂加重。所有患者的血清睾酮水平均降至去势水平（低于1.0纳克/毫升），尽管接受1.88毫克剂量的患者达到去势水平所需时间往往更长。血清TAP - 144水平在第一天升高，此后逐渐下降。在接受3.75毫克或更高剂量TAP - 144 - SR的患者组中，给药后4周内血清中均可检测到TAP - 144。基于I期研究结果，选择3.75毫克和7.5毫克的TAP - 144 - SR作为II期研究的剂量。II期研究作为一项多中心开放试验进行。B - D期前列腺癌患者每4周皮下注射一次3.75毫克（3.75毫克组）或7.5毫克（7.5毫克组）的TAP - 144 - SR，在12周内共注射3剂。3.75毫克组有51例患者，7.5毫克组有50例患者。这两种剂量均足以抑制血清促黄体生成素（LH）和促卵泡生成素（FSH）水平。首次给药后22天内血清睾酮降至去势水平，且在整个治疗期间维持这种抑制作用。根据实体癌化疗直接反应评估标准和NPCP标准，3.75毫克组的临床缓解率（CR + PR）为21%，7.5毫克组为22 - 24%。根据日本前列腺癌研究组标准，3.75毫克组的缓解率为51%，7.5毫克组为62%。3.75毫克组26%的患者出现不良反应，7.5毫克组为34%。（摘要截选至400字）
