Groves M D, Maor M H, Meyers C, Kyritsis A P, Jaeckle K A, Yung W K, Sawaya R E, Hess K, Bruner J M, Peterson P, Levin V A
The Brain Tumor Center, Department of Neuro-Oncology, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Int J Radiat Oncol Biol Phys. 1999 Aug 1;45(1):127-35. doi: 10.1016/s0360-3016(99)00122-4.
To conduct a Phase II study to evaluate the long-term efficacy and safety of high-dose 5'-bromodeoxyuridine (BrdU) and accelerated radiotherapy followed by procarbazine, lomustine (CCNU), and vincristine (PCV) chemotherapy in patients with glioblastoma multiforme.
Between 1994 and 1996, 88 patients were enrolled to receive 1.9 Gy of radiation three times a day for two 5-day cycles separated by 2 weeks; each 5-day cycle was preceded by a continuous 96-hour infusion of BrdU at a dose of 2.1 g/m2/day. After radiotherapy, patients received PCV chemotherapy.
Median survival for all 88 patients was 50 weeks. Seventy (79.5 %) received one or more courses of PCV; their median survival was 57 weeks. Covariates predictive of improved survival were gross total versus subtotal resection or biopsy (p = 0.0048) and radiation dose > or = 56 Gy (p = 0.019). While receiving BrdU, 47 patients (53%) suffered grade 3 or 4 thrombocytopenia or leukopenia; 22 patients (25%) suffered grade 3 or 4 dermatologic toxicity.
Survival was not extended in patients with glioblastoma or gliosarcoma who received BrdU at the dose and administration schedule used in this study. The BrdU dose used in this study resulted in substantial myelosuppressive and dermatologic toxicity.
开展一项II期研究，以评估高剂量5'-溴脱氧尿苷（BrdU）联合加速放疗，随后进行丙卡巴肼、洛莫司汀（CCNU）和长春新碱（PCV）化疗方案对多形性胶质母细胞瘤患者的长期疗效和安全性。
1994年至1996年期间，88例患者入组，接受每天3次、每次1.9 Gy的放疗，共两个5天周期，中间间隔2周；每个5天周期之前连续96小时输注剂量为2.1 g/m²/天的BrdU。放疗后，患者接受PCV化疗。
88例患者的中位生存期为50周。70例（79.5%）接受了一个或多个疗程的PCV治疗；他们的中位生存期为57周。预测生存期改善的协变量为大体全切与次全切或活检（p = 0.0048）以及放疗剂量≥56 Gy（p = 0.019）。在接受BrdU治疗期间，47例患者（53%）出现3级或4级血小板减少或白细胞减少；22例患者（25%）出现3级或4级皮肤毒性。
在本研究中，按照所用剂量和给药方案接受BrdU治疗的胶质母细胞瘤或胶质肉瘤患者生存期并未延长。本研究中使用的BrdU剂量导致了严重的骨髓抑制和皮肤毒性。
