Bevacizumab in Combination With Radiotherapy and Temozolomide for Patients With Newly Diagnosed Glioblastoma Multiforme. (12th January 2015)

• Record Type: Journal Article
• Authors: van Linde, Myra E.; Verhoeff, Joost J.C.; Richel, Dirk J.; van Furth, Wouter R.; Reijneveld, Jaap C.; Verheul, Henk M.W.; Stalpers, Lukas J.A.
• Is Part Of: Oncologist. Volume 20:Number 2(2015)
• Page Start: 107
• Page End: 108
• Publication Date: 2015-01-12
• Subjects: Oncology -- Periodicals; Tumors -- Periodicals; Cancérologie -- Périodiques; Tumeurs -- Périodiques; Oncology; Tumors; Neoplasms; Electronic journals; Periodicals; Periodicals; 616.994
• DOI: 10.1634/theoncologist.2014-0418
• Languages: English
• ISSNs: 1083-7159

Abstract

Abstract : Background: Patients with a newly diagnosed glioblastoma multiforme (GBM) have a high risk of recurrent disease with a dismal outcome despite intensive treatment of sequential surgery and chemoradiotherapy with temozolomide (TMZ), followed by TMZ as a single agent. Bevacizumab (BV) may increase response rates to chemotherapy in the recurrent treatment setting of GBM. We hypothesized that a neoadjuvant treatment strategy for patients with newly diagnosed GBM using chemoradiotherapy plus BV would improve resectability and thus survival. We performed a phase II trial of the treatment strategy of BV plus chemoradiation to determine the safety of this combination in patients who had already undergone primary surgery for their GBM. Methods: After a biopsy (6 patients) or a resection (13 patients) of a newly diagnosed GBM, 19 patients received radiotherapy (30 fractions of 2 Gy) in combination with daily TMZ 75 mg/m 2 and BV 10 mg/kg on days 1, 14, and 28, followed by 6 monthly cycles of TMZ 150–200 mg/m 2 on days 1–5. Results: The overall response rate was 26%. Three patients had a complete response after resection, and in two patients, a complete response after resection followed by chemoradiation plus BV was seen. No grade 3–4 toxicities were observed during combination treatment. The median progression‐free survival was 9.6 months (95% confidence interval [CI]: 4.3–14.4 months). The median overall survival was 16 months (95% CI: 8.1–26.3 months), similar to a matched control group that received standard chemoradiotherapy from our institution. Conclusion: Combination of bevacizumab with radiotherapy and TMZ is safe and feasible in patients with newly diagnosed GBM, but because of low response rates, this treatment strategy does not favor a neoadjuvant approach. Abstract : 摘要 研究背景 . 新诊断的多形性胶质母细胞瘤（GBM）患者即使接受了先手术，继而替莫唑胺（TMZ）化疗同步放疗，之后 TMZ 单药化疗的强化治疗方案，仍有高复发风险，预后不良。贝伐珠单抗（BV）可以提高化疗方案在复发 GBM 患者中的反应率。我们推测，一种针对新诊断 GBM 患者的新辅助治疗策略（即 TMZ 同步放化疗联合 BV）能提高该患者人群的手术切除率和生存。我们就此开展了一项 II 期临床研究，评价这一联合治疗方案在接受过首次手术切除的 GBM 患者中的安全性。 研究方法 . 19 例新诊断 GBM 患者在活检（6 例）和手术切除（13 例）后接受放疗（剂量 2 Gy，30 次分割）联合每天 TMZ 化疗（75 mg/m 2 ），在第 1、14、28 天时加用 BV（10 mg/kg）。此后给予 TMZ 单药治疗（150 ∼ 200 mg/m 2 ，第 1 ∼ 5 天，每 28 天一周期方案，共 6 个周期）。 研究结果 . 总体反应率为 26%。3 例患者在手术切除后达到完全缓解， 2 例患者在手术切除继以放化疗联合 BV 治疗后达到完全缓解。联合治疗期间未观察到 3 ∼ 4 级毒性反应。中位无进展生存（PFS）为 9.6 个月[95% 可信区间（CI）4.3 ∼ 14.4 个月]。中位总生存（OS）为 16 个月（95%CI 8.1 ∼ 26.3 月），与匹配的对照组（来自本机构，接受标准放化疗方案的患者）相似。 研究结论 . BV 联合 TMZ 同步放化疗方案在新诊断 GBM 患者中是安全可行的，但由于反应率较低，并不支持将其作为该患者人群的新辅助治疗策略。 The Oncologist 2015;20:107–108