Shah Gaurav D, Silver Joel S, Rosenfeld Steven S, Gavrilovic Igor T, Abrey Lauren E, Lassman Andrew B
Department of Neurology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
J Neurooncol. 2007 Nov;85(2):217-22. doi: 10.1007/s11060-007-9408-1. Epub 2007 Jun 27.
Reports suggest reasonable efficacy and minimal myelosuppression from combination imatinib and hydroxyurea for recurrent malignant glioma. We retrospectively reviewed 16 patients treated with this regimen who were evaluable for toxicity; 14 were also evaluable for response. The incidence of grade 3-4 hematologic toxicity was 25%. The best radiographic response, by Macdonald criteria, was partial response (PR) in three patients (21%), stable disease (SD) in four (29%), and progressive disease (PD) in seven (50%). One patient with a PR developed therapy-limiting hematologic toxicity on day 19 of treatment, progressing to grade 4 on day 64, and persisting until death on day 127 despite discontinuing both drugs. Another patient with PR and two of four patients with SD also developed grade 3 hematologic toxicity. All patients with grade 3-4 hematologic toxicity had disease control (PR or SD) as best radiographic response, whereas none with PD suffered grade 3-4 hematologic toxicity. Combining imatinib with hydroxyurea is effective in some patients with malignant glioma. However, myelosuppression can persist for months after discontinuing the regimen, precluding further chemotherapy. Disease control may also correlate with hematologic toxicity (p = 0.08), suggesting that glioma and marrow stem cells may share a common sensitivity to this chemotherapy regimen.
报告显示，伊马替尼与羟基脲联合用于复发性恶性胶质瘤具有合理的疗效且骨髓抑制作用最小。我们回顾性分析了16例接受该方案治疗且可评估毒性的患者；其中14例也可评估疗效。3-4级血液学毒性的发生率为25%。根据麦克唐纳标准，最佳影像学反应为3例患者（21%）出现部分缓解（PR），4例（29%）病情稳定（SD），7例（50%）病情进展（PD）。1例PR患者在治疗第19天出现限制治疗的血液学毒性，第64天进展为4级，尽管停用两种药物，但一直持续到第127天死亡。另1例PR患者以及4例SD患者中的2例也出现了3级血液学毒性。所有出现3-4级血液学毒性的患者最佳影像学反应均为病情得到控制（PR或SD），而所有病情进展的患者均未出现3-4级血液学毒性。伊马替尼与羟基脲联合应用对部分恶性胶质瘤患者有效。然而，停用该方案后骨髓抑制可能持续数月，从而无法进行进一步化疗。疾病控制也可能与血液学毒性相关（p = 0.08），这表明胶质瘤和骨髓干细胞可能对该化疗方案具有共同的敏感性。
