Paolozzi F P, Gaver R C, Newman N B, Poiesz B J, DeFino S, Louie A, Comis R L
Division of Hematology-Oncology, SUNY Health Science Center, Syracuse 13210.
Invest New Drugs. 1990 May;8(2):171-80. doi: 10.1007/BF00177253.
Bleomycin is an agent with significant antitumor efficacy whose major dose limiting toxicity is pulmonary fibrosis. Attempts have thus been made to identify congeners with reduced toxicity and with comparable or greater antitumor activity. Tallysomycin S10b is a bleomycin analogue possessing significantly greater potency, equal or reduced lung toxicity, and slightly greater antineoplastic activity when compared to the parent compound in preclinical studies. This report describes our experience with tallysomycin S10b in 30 patients with a variety of non-hematologic neoplasms. Pulmonary toxicity, occurring in 4 patients, was the major toxicity. The recommended cumulative dose of tallysomycin S10b was difficult to establish from the results of this study, as pulmonary toxicity appeared to be more idiosyncratic than dose- or schedule-dependent. The employment of more sensitive methods for detecting pulmonary toxicity in this study suggest that tallysomycin S10b may have reduced pulmonary toxicity compared to the parent compound. Both bleomycin and tallysomycin S10b have similar t1/2 beta half-lives of 2-4 h. Six patients had prolonged terminal elimination half-lives of tallysomycin S10b, but no clear relationship between this phenomenon and efficacy or toxicity was evident. No complete or partial responses occurred. Disease stabilization occurred in 4 of 15 patients with diagnoses of renal cell carcinoma, rectal cancer and lung cancer. Five of eight patients with non-measurable disease had stable disease, including one with mesothelioma, one with carcinoma of the head and neck, two with renal cell cancer and one with colon carcinoma.
博来霉素是一种具有显著抗肿瘤疗效的药物，其主要剂量限制性毒性为肺纤维化。因此，人们试图寻找毒性降低且具有相当或更高抗肿瘤活性的同类物。在临床前研究中， tallysomycin S10b是一种博来霉素类似物，与母体化合物相比，其效力显著更高，肺毒性相当或降低，抗肿瘤活性略高。本报告描述了我们对30例患有各种非血液系统肿瘤的患者使用tallysomycin S10b的经验。4例患者出现肺毒性，这是主要毒性。由于肺毒性似乎更具特异性而非剂量或给药方案依赖性，因此难以根据本研究结果确定tallysomycin S10b的推荐累积剂量。本研究中采用更敏感的方法检测肺毒性表明，与母体化合物相比，tallysomycin S10b的肺毒性可能降低。博来霉素和tallysomycin S10b的β半衰期相似，均为2 - 4小时。6例患者的tallysomycin S10b终末消除半衰期延长，但该现象与疗效或毒性之间无明显关系。未出现完全缓解或部分缓解。15例诊断为肾细胞癌、直肠癌和肺癌的患者中有4例病情稳定。8例不可测量疾病患者中有5例病情稳定，包括1例间皮瘤患者、1例头颈部癌患者、2例肾细胞癌患者和1例结肠癌患者。
