A phase II study of Didemnin B (NSC 325319) in advanced malignant melanoma: an Eastern Cooperative Oncology Group study (PB687).
A phase II study of Didemnin B (NSC 325319) in advanced malignant melanoma: an Eastern Cooperative Oncology Group study (PB687).
复制标题
Didemnin B (NSC 325319) 治疗晚期恶性黑色素瘤的 II 期研究：东部肿瘤合作组研究 (PB687)。
DOI：
10.1023/a:1006110431250
复制
发表时间：
1998
影响因子：
3.4
通讯作者：
Borden,E
中科院分区：
文献类型：
--
作者：
Hochster,H;Oratz,R;Ettinger,DS;Borden,E
目的：dideminin B是一种新型的海洋天然产物，含有特殊的氨基酸片段。在人类肿瘤干细胞试验中，该药物显示出有希望的临床前抗肿瘤活性，包括对B16黑色素瘤和黑色素瘤分离株的活性。方法：我们进行了一项II期研究，在cremoophor中给予dideminb，起始剂量为4.2 mg/m2/IV，每28天。可测量的转移性或晚期恶性黑色素瘤患者符合条件。所有患者先前未接受化疗，表现状态为0或1。在第2和第3周期中，剂量分别增加到4.9和5.6 mg/m2。结果：19例患者入组治疗，平均每个患者一个周期。这些患者中有8人因毒性退出研究，其中7人在第一或第二周期出现类过敏反应。一名患者在3个周期后因严重肌病退出研究，这是一种新描述的毒性。2例无法评估疗效，5例被认为稳定，包括1例在第一个周期出现软组织疾病的短暂PR。另一名患者病情稳定12个周期后才进展，一名患者在3个周期后选择性退出研究，共7名患者病情稳定。一名患者有可测量的部分缓解（PR），但由于严重的肌病（当时新描述的毒性），在三个周期后退出研究。未见血液学毒性。用止吐剂控制恶心呕吐。结论：本研究不确定didemin B在黑色素瘤中的活性。活动的迹象是可见的，特别是在软组织肿块，但由于发生类过敏反应，大量患者不能完全评估活动。这项研究不排除临床上重要的dideminb活性水平。
Purpose: Didemnin B is a novel marine natural product cyclic depsipeptide containing unusual amino acid moieties. This agent demonstrates promising preclinical antitumor activity, including activity against B16 melanoma and against melanoma isolates in the human tumor stem cell assay.Methods: We conducted a phase II study of Didemnin B, given in Cremophor, at a starting dose of 4.2 mg/m2/IV q 28 days. Patients with measurable metastatic or advanced malignant melanoma were eligible. All patients were previously untreated with chemotherapy and had performance status 0 or 1. Doses were escalated to 4.9 and 5.6 mg/m2 in cycles 2 and 3, respectively.Results: Nineteen patients were entered and treated with a median of one cycle per patient. Eight of these patients went off study for toxicity including 7 with anaphylactoid reactions in the first or second cycle. One patient went off study after 3 cycles with severe myopathy, a newly described toxicity. Two were not evaluable for response and five were considered stable, including one patient with a transient PR of soft tissue disease in the first cycle. Another patient had stable disease for twelve cycles before progressing and one went off study electively after 3 cycles, for a total of 7 patients with stable disease. One patient with a measurable partial remission (PR) and went off study after three cycles due to severe myopathy, a then newly-described toxicity. No hematologic toxicity was seen. Nausea and vomiting were controlled with anti-emetics.Conclusions: This study was indeterminate with respect to the activity of Didemnin B in melanoma. Signs of activity were seen, particularly in soft tissue masses, though a large number of patients could not be evaluated fully for activity due to the occurrence of anaphylactoid reactions. This study does not preclude a clinically important level of activity for Didemnin B.