Adamson P C, Zimm S, Ragab A H, Steinberg S M, Balis F, Kamen B A, Vietti T J, Gillespie A, Poplack D G
Pediatric Branch, National Cancer Institute, Bethesda, MD 20892.
Cancer Chemother Pharmacol. 1990;26(5):343-4. doi: 10.1007/BF02897290.
A phase II pediatric trial of a continuous intravenous infusion of 6-mercaptopurine (6-MP) in patients with refractory solid tumors or lymphoma was performed. The dosing schedule of 50 mg/m2 per hour for 48 h was chosen to produce optimal cytotoxic concentrations of 6-MP. There were no complete or partial responses in the 40 patients entered in the trial. Accrual was sufficient for the conclusion to be drawn that there was greater than 95% probability that the true response rate was no greater than 22% and 26% in osteosarcoma and Ewing's sarcoma, respectively. Dose-limiting toxicity was observed in one-third of the patients and included reversible hepatotoxicity, myelosuppression, and mucositis. The excellent penetration of drug into the cerebrospinal fluid (CSF) suggests that future trials of this intravenous dosing schedule should be conducted on tumors of the CNS.
开展了一项针对难治性实体瘤或淋巴瘤患儿的II期试验，对其持续静脉输注6-巯基嘌呤（6-MP）。选择每小时50mg/m²、持续48小时的给药方案，以产生6-MP的最佳细胞毒性浓度。入组该试验的40例患者中无完全缓解或部分缓解。病例数足以得出结论：骨肉瘤和尤因肉瘤的真实缓解率分别不高于22%和26%的概率大于95%。三分之一的患者出现剂量限制性毒性，包括可逆性肝毒性、骨髓抑制和粘膜炎。药物在脑脊液（CSF）中的良好渗透性表明，未来应针对中枢神经系统肿瘤开展该静脉给药方案的试验。
