Wehbe T, Glantz M, Choy H, Glantz L, Cortez S, Akerley W, Mills P, Cole B
Rhode Island Hospital, USA.
J Neurooncol. 1998 Sep;39(3):245-51. doi: 10.1023/a:1005710710418.
The new anticancer agent Taxol appears to potentiate the effects of radiation on brain tumor cell lines in vitro and was recently evaluated by our group as a radiosensitizer in a phase I study for primary brain tumors. In that study, we administered Taxol as a three-hour IV infusion repeated every week for six weeks and gave daily cranial irradiation concurrently for a total of 6000 rads. We reviewed the charts of the 60 patients who participated in the study, and identified twelve patients who underwent a second surgery after treatment because of progressive symptoms and an enlarging intracranial mass on MRI. Pathologically, each patient showed prominent radionecrosis, and other evidence of accelerated radiation changes (confluent areas of coagulative necrosis, bizarre nuclei, marked thickening and fibrinoid changes in multiple blood vessels). These changes were noted many weeks earlier than would be expected after radiation therapy alone and were independent of age, and tumor histology. We postulate that the accelerated radiation changes may be due to the radiation sensitizing effects of Taxol. We also noted a change of the pattern of tumor recurrence, compared to historic reports, and a dose-necrosis relationship where the resected tumor is formed completely of necrotic tissue in patients who received 150 mg/m2 or higher dose of Taxol. These observations may be of significance for future study design.
新型抗癌药物紫杉醇似乎能增强辐射对体外脑肿瘤细胞系的作用，并且最近我们小组在一项针对原发性脑肿瘤的I期研究中对其作为放射增敏剂进行了评估。在该研究中，我们以每周重复一次、每次静脉输注三小时、共持续六周的方式给予紫杉醇，并同时每日进行颅脑照射，总计6000拉德。我们查阅了参与该研究的60例患者的病历，确定了12例患者，这些患者在治疗后因症状进展以及MRI显示颅内肿块增大而接受了二次手术。病理检查显示，每位患者均有明显的放射性坏死以及其他加速放射改变的证据（凝固性坏死融合区域、奇异核、多条血管显著增厚和纤维蛋白样改变）。这些改变比单纯放疗后预期的时间要早很多周出现，且与年龄和肿瘤组织学无关。我们推测加速的放射改变可能归因于紫杉醇的放射增敏作用。与既往报道相比，我们还注意到肿瘤复发模式的改变，以及在接受150mg/m²或更高剂量紫杉醇的患者中存在剂量 - 坏死关系，即切除的肿瘤完全由坏死组织构成。这些观察结果可能对未来的研究设计具有重要意义。
