Woolley P V, Freiha F S, Smith D C, Carlson L, Hofacker J, Quinn N, Grove W, Trump D L
University of Pittsburgh Cancer Institute, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.
Cancer Chemother Pharmacol. 1999;44(6):511-7. doi: 10.1007/s002800051126.
To assess the antitumor activity of the benzothiopyranoindazole CI-958 ¿5-[(2-aminomethyl)amino]-2-[2-(diethylamino)ethyl]-2H- [l]benzothiopyrano[4,3,2-cd]-indazol-8-ol trihydrochloride¿ in hormone-resistant prostate carcinoma, using an intravenous dose of 700 mg/m(2) every 3 weeks.
Patients eligible for this study had advanced prostate carcinoma that had failed hormonal treatment. Changes in an initially elevated prostate-specific antigen (PSA) level and regression of objectively measurable disease were used as response criteria.
All 33 patients enrolled were evaluated. Of 30 with elevated PSA levels, 6 had a >50% decline maintained for >30 days; response durations ranged from 105 to 623 days. Eleven patients had objectively measurable disease; two had partial responses (lasting 316 and 461 days) consisting of shrinkage of retroperitoneal nodes and of masses surrounding the rectum and bladder. The survival of all responding patients ranged from 366 days to 709 days and the median survival of all patients was 12 months (range 1-23 + months). Neutropenia was common, but thrombocytopenia was not. Nonhematologic side effects included nausea, vomiting, anorexia, asthenia, and chills, but were usually mild. The drug caused phlebitis when given into peripheral veins and central venous administration is recommended. No consistent reductions in cardiac function were documented by sequential assessment of left ventricular ejection fractions.
CI-958 has modest but definite antitumor activity in hormone-resistant prostate carcinoma. Its toxicities include neutropenia, nausea, vomiting, anorexia, asthenia, chills and phlebitis.
使用每3周静脉注射剂量为700mg/m²的苯并噻吩并吲哚唑CI-958（5-[(2-氨基甲基)氨基]-2-[2-(二乙氨基)乙基]-2H-[1]苯并噻吩并[4,3,2-cd]吲哚-8-醇三盐酸盐）评估其在激素抵抗性前列腺癌中的抗肿瘤活性。
符合本研究条件的患者患有晚期前列腺癌且激素治疗失败。最初升高的前列腺特异性抗原（PSA）水平的变化以及客观可测量疾病的消退被用作反应标准。
所有33名入组患者均接受了评估。在30名PSA水平升高的患者中，6名患者的PSA水平下降超过50%并维持超过30天；反应持续时间为105至623天。11名患者有客观可测量的疾病；两名患者有部分反应（持续316天和461天），表现为腹膜后淋巴结以及直肠和膀胱周围肿块缩小。所有有反应患者的生存期为366天至709天，所有患者的中位生存期为12个月（范围1至23 +个月）。中性粒细胞减少很常见，但血小板减少不常见。非血液学副作用包括恶心、呕吐、厌食、乏力和寒战，但通常较轻。药物经外周静脉给药时会引起静脉炎，建议采用中心静脉给药。通过连续评估左心室射血分数未记录到一致的心脏功能降低。
CI-958在激素抵抗性前列腺癌中具有适度但明确的抗肿瘤活性。其毒性包括中性粒细胞减少、恶心、呕吐、厌食、乏力、寒战和静脉炎。
