High-dose VP-16-213 and autologous bone marrow transplantation for refractory malignancies: a phase I study.
High-dose VP-16-213 and autologous bone marrow transplantation for refractory malignancies: a phase I study.
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高剂量 VP-16-213 和自体骨髓移植治疗难治性恶性肿瘤：I 期研究。
DOI：
10.1200/jco.1983.1.11.701
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发表时间：
1983
期刊：
影响因子：
--
通讯作者：
F. Greco
中科院分区：
文献类型：
--
作者：
S. Wolff;M. Fer;C. Mckay;K. Hande;J. Hainsworth;F. Greco
VP-16-213, a congener of epipodophyllotoxin, is a useful chemotherapeutic agent especially against small-cell carcinoma of the lung, germ cell carcinoma, and lymphoma. The standard dose of this drug is limited by myelosuppression. Autologous transplantation of cryopreserved bone marrow assures the restoration of hematopoiesis after marrow ablative cytotoxic therapy. By using this technique, VP-16-213 was dose-escalated using a Fibonacci scheme from the previous highest dose administered to humans (1,500 mg/m2) to 2,700 mg/m2 (900 mg/m2 per day for three consecutive days). At 2,700 mg/m2, severe extramedullary toxicity of the mucous membranes was observed in three of three courses. At the next highest dose (2,400 mg/m2), two of 18 courses (11%, p less than 0.01) resulted in severe mucositis, thus defining this dose as the maximally tolerated dose based on extramedullary toxicities. As anticipated, myelotoxicity was severe but based on the kinetics of marrow recovery, VP-16-213 in these doses appeared not to be marrow ablative. Based on responses observed in this study, high-dose VP-16-213 should be explored in phase II studies or used in combination chemotherapy.
