Optimizing cancer radiotherapy with 2-deoxy-D-glucose - Dose escalation studies in patients with glioblastoma multiforme
Optimizing cancer radiotherapy with 2-deoxy-D-glucose - Dose escalation studies in patients with glioblastoma multiforme
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DOI：
10.1007/s00066-005-1320-z
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发表时间：
2005-08-01
影响因子：
3.1
通讯作者：
Jain, V
中科院分区：
文献类型：
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作者：
Singh, DH;Banerji, AK;Jain, V
背景与目的：在几种类型的恶性肿瘤中，较高的葡萄糖利用率和糖酵解率通常与不良预后相关。自己早期对模型系统的研究表明，不可代谢的葡萄糖类似物2-脱氧-d -葡萄糖（2-DG）可以选择性地使癌细胞敏感，同时保护正常细胞，以剂量依赖的方式增强放射治疗的疗效。I/II期临床试验表明，在脑胶质瘤患者中，口服剂量为200 mg/kg体重（BW）的2-DG与大剂量γ辐射的组合耐受性良好。由于较高的2-DG剂量有望提高治疗效果，目前的研究是为了检查多形胶质母细胞瘤患者在联合治疗（2-DG +放疗）期间增加2-DG剂量的耐受性和安全性。患者和方法：组织学证实的多形性胶质母细胞瘤（WHO标准）未经治疗的患者纳入研究。每周7次Co-60 γ射线（5 Gy/次）被递送到肿瘤体积（术前CT/MRI评估）加上3 cm边缘。禁食过夜后，在照射前30分钟口服2-DG剂量（200-250-300 mg/kg BW）。通过监测生命参数和副反应，研究急性毒性和耐受性。对存活患者的晚期放射损伤和治疗反应进行放射学和临床研究。结果：多数患者出现类似低血糖的短暂性副作用。耐受性和患者对联合治疗的依从性非常好，直到2-DG剂量为250 mg/kg BW。然而，在300 mg/kg体重的较高剂量下，6名患者中有2名非常不安，无法完成治疗，尽管即使在该剂量下也未观察到重要参数的显着变化。在接受完整治疗并在治疗后11至46个月存活的10名患者中，有7名在随访期间未观察到正常脑组织的明显损伤。结论：2-DG口服联合大剂量放疗（5 Gy/次/周）对胶质母细胞瘤患者安全、耐受，无急性毒性，对正常脑无后期放射损伤。需要进一步的临床研究来评估联合治疗的疗效。
Background and Purpose: Higher rates of glucose utilization and glycolysis generally correlate with poor prognosis in several types of malignant tumors. Own earlier studies on model systems demonstrated that the nonmetabolizable glucose analog 2-de-oxy-D-gLucose (2-DG) could enhance the efficacy of radiotherapy in a dose-dependent manner by selectively sensitizing cancer cells while protecting normal cells. Phase I/II clinical trials indicated that the combination of 2-DG, at an oral dose of 200 mg/kg body weight (BW), with large fractions of gamma-radiation was well tolerated in cerebral glioma patients. Since higher 2-DG doses are expected to improve the therapeutic gain, present studies were undertaken to examine the tolerance and safety of escalating 2-DG dose during combined treatment (2-DG + radiotherapy) in glioblastoma multiforme patients.Patients and Methods: Untreated patients with histologically proven glioblastoma multiforme (WHO criteria) were included in the study. Seven weekly fractions of Co-60 gamma-rays (5 Gy/fraction) were delivered to the tumor volume (presurgical CT/MRI evaluation) plus 3 cm margin. Escalating 2-DG doses (200-250-300 mg/kg BW) were administered orally 30 min before irradiation after overnight fasting. Acute toxicity and tolerance were studied by monitoring the vital parameters and side effects. Late radiation damage and treatment responses were studied radiologically and clinically in surviving patients.Results: Transient side effects similar to hypoglycemia were observed in most of the patients. Tolerance and patient compliance to the combined treatment were very good up to a 2-DG dose of 250 mg/kg BW. However, at the higher dose of 300 mg/kg BW, two out of six patients were very restless and could not complete treatment, though significant changes in the vital parameters were not observed even at this dose. No significant damage to the normal brain tissue was observed during follow-up in seven out of ten patients who received complete treatment and survived between 11 and 46 months after treatment.Conclusion: Oral administration of 2-DG combined with Large fractions of radiation (5 Gy/fraction/week) is safe and could be tolerated in glioblastoma patients without any acute toxicity and Late radiation damage to the normal brain. Further clinical studies to evaluate the efficacy of the combined treatment are warranted.