A phase II study of bevacizumab plus erlotinib for gemcitabine-refractory metastatic pancreatic cancer
A phase II study of bevacizumab plus erlotinib for gemcitabine-refractory metastatic pancreatic cancer
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DOI：
10.1007/s00280-010-1257-5
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发表时间：
2010-11-01
影响因子：
3
通讯作者：
Tempero, Margaret A.
中科院分区：
文献类型：
--
作者：
Ko, Andrew H.;Venook, Alan P.;Tempero, Margaret A.
一线化疗后进展的转移性胰腺癌患者没有标准治疗。基于同时抑制VEGF和EGFR的潜在叠加或协同活性，我们进行了一项II期研究，评估贝伐单抗联合厄洛替尼在该患者人群中的应用，转移性胰腺癌患者，ECOG体力状态0-1，既往接受过1-3种全身治疗（至少一种基于吉西他滨）。治疗包括贝伐单抗15 mg/kg每21天加厄洛替尼150 mg每日。36例患者入组，包括8例既往接受VEGF靶向治疗和9例既往接受厄洛替尼治疗。中位治疗周期数为2（范围，1-7）。常见毒性包括皮疹（72%）、腹泻（25%）、静脉血栓栓塞事件（15%）和高血压（11%）。一名患者表现出部分反应，其他七名患者病情稳定> 2个周期。在4/26例基线水平> 2x ULN的患者中观察到CA 19 -9下降千分之25%。估计的中位进展时间为40天（95% CI，35-41天），中位生存期为102天（95% CI，74-117天），6个月生存率为22%。基线循环内皮细胞浓度（CD 45（-）/CD 34（+）/CD 31（+））与总生存率呈负相关。贝伐单抗和厄洛替尼联合治疗吉西他滨难治性转移性胰腺癌是安全的，但相对无效。未来的研究应侧重于在这一具有挑战性的人群中细化可能从一线治疗以外的治疗中获益的患者子集。
No standard of care exists for patients with metastatic pancreatic cancer following progression on first-line chemotherapy. Based on potential for additive or synergistic activity by concurrent inhibition of VEGF and EGFR, we conducted a phase II study evaluating the combination of bevacizumab plus erlotinib in this patient population.Patients with metastatic pancreatic adenocarcinoma, ECOG performance status 0-1, and previous exposure to 1-3 systemic therapies (at least one gemcitabine-based) were eligible. Treatment consisted of bevacizumab 15 mg/kg every 21 days plus erlotinib 150 mg daily.Thirty-six patients were enrolled, including eight who had previously received VEGF-targeted therapy and nine prior erlotinib. Median number of treatment cycles was 2 (range, 1-7). Common toxicities included rash (72%), diarrhea (25%), venous thromboembolic events (15%), and hypertension (11%). One patient demonstrated partial response and seven others stable disease for > 2 cycles. CA19-9 decline a parts per thousand yen25% was observed in 4/26 patients with baseline levels > 2x ULN. Estimated median time to progression was 40 days (95% CI, 35-41 days) and median survival 102 days (95% CI, 74-117 days), with a 6-month survival rate of 22%. Baseline concentration of circulating endothelial cells (CD45(-)/CD34(+)/CD31(+)) was inversely associated with overall survival.The combination of bevacizumab and erlotinib is safe but relatively ineffective in patients with gemcitabine-refractory metastatic pancreatic cancer. Future studies should focus on refining subsets of patients in this challenging population likely to benefit from treatment beyond first-line.