Phase II trial of bryostatin-1 in combination with cisplatin in patients with recurrent or persistent epithelial ovarian cancer: a California cancer consortium study.
Phase II trial of bryostatin-1 in combination with cisplatin in patients with recurrent or persistent epithelial ovarian cancer: a California cancer consortium study.
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苔藓抑素-1 联合顺铂治疗复发性或持续性上皮性卵巢癌患者的 II 期试验：加州癌症联盟研究。
DOI：
10.1007/s10637-010-9557-5
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发表时间：
2012
影响因子：
3.4
通讯作者：
Doroshow,JamesH
中科院分区：
文献类型：
--
作者：
MorganJr,RobertJ;Leong,Lucille;Chow,Warren;Gandara,David;Frankel,Paul;Garcia,Agustin;Lenz,Heinz-Josef;Doroshow,JamesH
背景加州癌症协会已经进行了一项输注性苔藓抑素与顺铂联合的II期试验，苔藓抑素是一种从海洋无脊椎苔藓虫Bugula Neritina中分离出来的蛋白激酶C抑制剂，Bugula Neritina是外肛门的一员，复发性铂敏感或耐药卵巢癌（OC）患者（pts）。m2连续输注72 h后，给予顺铂50 mg/m2。每3周重复一个周期。剂量选择的基础上获得的CCC在人口的混合tumor types.Results8例复发或持续上皮OC的患者的I期数据接受23个周期的治疗。所有患者既往均接受过铂类化疗; 2例患者既往接受过1个疗程，5例患者既往接受过2个疗程，1例患者既往接受过3个疗程的化疗。中位年龄为64岁（范围32-72），Karnofsky体能状态为90（范围80-100）。中位化疗周期为3个（范围：1-5）。中位无进展生存期和总生存期分别为3个月和8.2个月。最佳缓解包括2例部分缓解（1例铂类耐药患者）、3例疾病稳定患者和3例进展。所有患者均发生3级或4级毒性，包括6例患者的重度肌痛/疼痛/疲劳/虚弱，以及另外2例患者的重度恶心/呕吐/便秘。一个PT经历了癫痫发作和肝功能测试升高，在一个other.ConclusionsA适度的反应率观察与苔藓抑素和顺铂的组合治疗复发性或持续性卵巢癌患者。然而，在该患者人群中观察到的毒性特征（主要是重度肌痛）排除了耐受性，并阻止了在该剂量和方案下对该联合用药进行进一步研究。OC患者的铂预暴露可能加重了观察到的毒性。应谨慎选择OC患者中II期试验药物剂量，这些剂量是由其他肿瘤类型患者的I期试验确定的。
BackgroundThe California Cancer Consortium has performed a Phase II trial of infusional bryostatin, a protein kinase C inhibitor isolated from the marine invertebrate bryozoan, Bugula Neritina, a member of the phylum Ectoprocta, in combination with cisplatin, in patients (pts) with recurrent platinum-sensitive or resistant ovarian cancer (OC).MethodsPts received bryostatin 45 mcg/m2as a 72 h continuous infusion followed by cisplatin 50 mg/m2. Cycles were repeated every 3 weeks. Dosages were chosen based on phase I data obtained by the CCC in a population of pts with mixed tumor types.ResultsEight pts with recurrent or persistent epithelial OC received 23 cycles of treatment. All pts had received previous platinum-based chemotherapy; two pts had received one prior course, five had received two prior courses, and one had received three prior courses of chemotherapy. The median age was 64 (range 32–72), and Karnofsky performance status 90 (range 80–100). A median of 3 cycles of chemotherapy were delivered (range: 1–5). The median progression-free and overall survivals were 3 and 8.2 months respectively. Best responses included two partial responses (one in a platinum-resistant pt), three pts with stable disease, and three progressions. All pts experienced Grade 3 or 4 toxicities including severe myalgias/pain/fatigue/asthenia in six pts, and severe nausea/vomiting/constipation in two other pts. One pt experienced a seizure and liver function tests were elevated in one other.ConclusionsA modest response rate is observed in pts with recurrent or persistent ovarian cancer treated with the combination of bryostatin and cisplatin. The toxicity profile, however, observed in this pt population (primarily severe myalgias), precludes tolerability and prevents this combination from further investigation at this dose and schedule. It is possible that platinum pre-exposure in OC patients exacerbates observed toxicity. Phase II dosages of investigational agents in OC pts that are determined by phase I trials in pts with other tumor types should be chosen cautiously.