BACKGROUND:Advances in comprehension of molecular biology of glioblastoma (GBM) have led to the development of targeted therapies. The aim of the present study was to evaluate the efficacy and safety of a targeted therapeutic approach in which administration of bevacizumab and erlotinib was tailored on the molecular profile of recurrent GBM.
METHODS:We prospectively enrolled ten adult patients suffering from recurrent GBM who had undergone surgical resection and standard chemo-radiotherapy. Tumor tissue was assessed for the expression of EGFRvIII and MGMT promoter methylation by RT-PCR, and for PTEN and VEGF expression by immunohistochemistry. Normal PTEN status was required for inclusion. Patients with VEGF overexpressing tumors (10/10) were treated with bevacizumab (10 mg/kg iv every 2 weeks in 6-week cycles); patients whose tumor expressed EGFRvIII (4/10) added erlotinib (150 mg/day orally; 300 mg/day if on enzyme-inducing antiepileptic drugs). Therapy was continued until disease progression or unacceptable toxicity. Primary endpoints of the study were response rate (RR), 6-month progression-free survival (PFS-6), and safety profile.
RESULTS:The RR and PFS-6 were 100 % (4/4) and 50 % (3/6) in patients treated with bevacizumab+erlotinib (n = 4) and bevacizumab (n = 6), respectively. In the whole cohort (n = 10), RR and PFS-6 were both 70 % (7/10); median PFS and overall survival (OS) were 8.0 (3.0-31.0) and 9.5 (5.0-31.0) months, respectively. No grade 3/4 adverse events were observed; three patients treated with bevacizumab+erlotinib displayed grade 1/2 rash not requiring dose reduction; one patient treated with bevacizumab developed intratumoral hemorrhage requiring treatment discontinuation.
CONCLUSION:To our knowledge, this is the first study on recurrent GBM in which administration of bevacizumab and erlotinib was tailored on the molecular profile of the patient's tumor. Although we treated a limited number of patients, we obtained significantly higher RR and PFS-6 than those reported in a previous trial lacking molecular tumor analysis.
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【Targeted therapy with bevacizumab and erlotinib tailored to the molecular profile of patients with recurrent glioblastoma. Preliminary experience.].
【贝伐单抗和厄洛替尼的靶向治疗针对复发性胶质母细胞瘤患者的分子情况进行了定制。初步经验。】
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DOI：10.1007/s00701-012-1536-5文章类型：杂志文章
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背景：胶质母细胞瘤（GBM）分子生物学的研究进展已导致靶向治疗的发展。本研究的目的是评估靶向治疗方法的疗效和安全性，在该治疗方法中，贝伐单抗和厄洛替尼的给药根据复发性GBM的分子特征进行了调整。
方法：我们前瞻性招募了10例患有GBM复发的成人患者，这些患者均接受了手术切除和标准化学放疗。通过RT-PCR评估肿瘤组织中EGFRvIII和MGMT启动子甲基化的表达，并通过免疫组织化学评估PTEN和VEGF的表达。包括在内需要正常的PTEN状态。使用贝伐单抗（6周周期内，每2周静脉注射10 mg / kg）治疗VEGF过表达肿瘤（10/10）的患者；肿瘤表达EGFRvIII（4/10）的患者加用厄洛替尼（口服150毫克/天；如果使用酶诱导的抗癫痫药，则为300毫克/天）。继续治疗直至疾病进展或出现不可接受的毒性。该研究的主要终点是缓解率（RR），6个月无进展生存期（PFS-6）和安全性。
结果：接受贝伐单抗厄洛替尼（n = 4）和贝伐单抗（n = 6）治疗的患者的RR和PFS-6分别为100％（4/4）和50％（3/6）。在整个队列中（n = 10），RR和PFS-6均为70％（7/10）; PFS中位数和总生存期（OS）分别为8.0（3.0-31.0）和9.5（5.0-31.0）个月。没有观察到3/4级不良事件；三名接受贝伐单抗厄洛替尼治疗的患者出现1/2级皮疹，无需降低剂量；一名接受贝伐单抗治疗的患者发生了肿瘤内出血，需要中止治疗。
结论：据我们所知，这是关于复发性GBM的第一项研究，其中根据患者肿瘤的分子特征量身定制了贝伐单抗和厄洛替尼的给药。尽管我们治疗的患者数量有限，但与先前缺乏分子肿瘤分析的试验中报道的结果相比，我们获得了更高的RR和PFS-6。
方法：我们前瞻性招募了10例患有GBM复发的成人患者，这些患者均接受了手术切除和标准化学放疗。通过RT-PCR评估肿瘤组织中EGFRvIII和MGMT启动子甲基化的表达，并通过免疫组织化学评估PTEN和VEGF的表达。包括在内需要正常的PTEN状态。使用贝伐单抗（6周周期内，每2周静脉注射10 mg / kg）治疗VEGF过表达肿瘤（10/10）的患者；肿瘤表达EGFRvIII（4/10）的患者加用厄洛替尼（口服150毫克/天；如果使用酶诱导的抗癫痫药，则为300毫克/天）。继续治疗直至疾病进展或出现不可接受的毒性。该研究的主要终点是缓解率（RR），6个月无进展生存期（PFS-6）和安全性。
结果：接受贝伐单抗厄洛替尼（n = 4）和贝伐单抗（n = 6）治疗的患者的RR和PFS-6分别为100％（4/4）和50％（3/6）。在整个队列中（n = 10），RR和PFS-6均为70％（7/10）; PFS中位数和总生存期（OS）分别为8.0（3.0-31.0）和9.5（5.0-31.0）个月。没有观察到3/4级不良事件；三名接受贝伐单抗厄洛替尼治疗的患者出现1/2级皮疹，无需降低剂量；一名接受贝伐单抗治疗的患者发生了肿瘤内出血，需要中止治疗。
结论：据我们所知，这是关于复发性GBM的第一项研究，其中根据患者肿瘤的分子特征量身定制了贝伐单抗和厄洛替尼的给药。尽管我们治疗的患者数量有限，但与先前缺乏分子肿瘤分析的试验中报道的结果相比，我们获得了更高的RR和PFS-6。
