Introduction Glioblastoma (GBM) has poor survival with standard treatment. Experimental data suggest potential for metabolic treatment with low carbohydrate ketogenic diet (KD). Few human studies of KD in GBM have been done, limited by difficulty and variability of the diet, compliance, and feasibility issues. We have developed a novel KD approach of total meal replacement (TMR) program using standardized recipes with ready-made meals. This pilot study evaluated feasibility, safety, tolerability, and efficacy of GBM treatment using TMR program with “classic” 4:1 KD. Method GBM patients were treated in an open-label study for 6 months with 4:1 [fat]:[protein + carbohydrate] ratio by weight, 10 g CH/day, 1600 kcal/day TMR. Patients were either newly diagnosed (group 1) and treated adjunctively to radiation and temozolomide or had recurrent GBM (group 2). Patients checked blood glucose and blood and urine ketone levels twice daily and had regular MRIs. Primary outcome measures included retention, treatment-emergent adverse events (TEAEs), and TEAE-related discontinuation. Secondary outcome measures were survival time from treatment initiation and time to MRI progression. Results Recruitment was slow, resulting in early termination of the study. Eight patients participated, 4 in group 1 and 4 in group 2. Five (62.5%) subjects completed the 6 months of treatment, 4/4 subjects in group 1 and 1/4 in group 2. Three subjects stopped KD early: 2 (25%) because of GBM progression and one (12.5%) because of diet restrictiveness. Four subjects, all group 1, continued KD on their own, three until shortly before death, for total of 26, 19.3, and 7 months, one ongoing. The diet was well tolerated. TEAEs, all mild and transient, included weight loss and hunger ( n = 6) which resolved with caloric increase, nausea ( n = 2), dizziness ( n = 2), fatigue, and constipation ( n = 1 each). No one discontinued KD because of TEAEs. Seven patients died. For these, mean (range) survival time from diet initiation was 20 months for group 1 (9.5–27) and 12.8 months for group 2 (6.3–19.9). Mean survival time from diagnosis was 21.8 months for group 1 (11–29.2) and 25.4 months for group 2 ( 13.9–38.7). One patient with recurrent GBM and progression on bevacizumab experienced a remarkable symptom reversal, tumor shrinkage, and edema resolution 6–8 weeks after KD initiation and survival for 20 months after starting KD. Conclusion Treatment of GBM patients with 4:1 KD using total meal replacement program with standardized recipes was well tolerated. The small sample size limits efficacy conclusions. Trial registration NCT01865162 registered 30 May 2013, and NCT02302235 registered 26 November 2014, https://clinicaltrials.gov/

中文翻译：

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用“经典”4:1 生酮饮食全餐替代治疗多形性胶质母细胞瘤

介绍 胶质母细胞瘤 (GBM) 在标准治疗下的存活率很低。实验数据表明低碳水化合物生酮饮食（KD）代谢治疗的潜力。由于饮食的难度和可变性、依从性和可行性问题，很少有人对 GBM 中的 KD 进行过人体研究。我们开发了一种全新的 KD 方法来进行全餐替代 (TMR) 计划，使用标准食谱和现成餐。这项初步研究评估了使用 TMR 计划和“经典”4:1 KD 治疗 GBM 的可行性、安全性、耐受性和有效性。方法 GBM 患者在一项开放标签研究中接受 6 个月的治疗，[脂肪]：[蛋白质 + 碳水化合物]重量比为 4:1，10 g CH/天，1600 kcal/天 TMR。患者要么是新诊断的（第 1 组）并接受了放疗和替莫唑胺的辅助治疗，要么是复发性 GBM（第 2 组）。患者每天两次检查血糖、血液和尿酮水平，并定期进行 MRI 检查。主要结果指标包括保留、治疗出现的不良事件 (TEAE) 和 TEAE 相关的停药。次要结果指标是从治疗开始的生存时间和到 MRI 进展的时间。结果招募缓慢，导致研究提前终止。8 名患者参加，第 1 组 4 名，第 2 组 4 名。5 名 (62.5%) 受试者完成了 6 个月的治疗，第 1 组 4/4 名受试者和第 2 组 1/4 名受试者。三名受试者提前停止 KD：2 ( 25%）是因为 GBM 进展，1 人（12.5%）是因为饮食限制。四个科目，所有第 1 组，自己继续 KD，三个直到死前不久，总共 26、19.3 和 7 个月，一个正在进行。饮食耐受性良好。TEAE 都是轻微和短暂的，包括体重减轻和饥饿 (n = 6)，随着热量增加、恶心 (n = 2)、头晕 (n = 2)、疲劳和便秘 (各​​ n = 1) 而消退。没有人因为 TEAE 而停用 KD。七名患者死亡。对于这些，从饮食开始的平均（范围）存活时间对于第 1 组 (9.5-27) 为 20 个月，对于第 2 组 (6.3-19.9) 为 12.8 个月。第 1 组 (11-29.2) 和第 2 组 (13.9-38.7) 从诊断开始的平均生存时间为 21.8 个月和 25.4 个月。一名复发性 GBM 和贝伐珠单抗进展的患者在 KD 开始后 6-8 周经历了显着的症状逆转、肿瘤缩小和水肿消退，并在开始 KD 后存活了 20 个月。结论 使用标准化食谱的全膳食替代方案治疗 4:1 KD 的 GBM 患者具有良好的耐受性。小样本量限制了疗效结论。试验注册 NCT01865162 注册于 2013 年 5 月 30 日，NCT02302235 注册于 2014 年 11 月 26 日，https://clinicaltrials.gov/