University of California at San Francisco Helen Diller Family Comprehensive Cancer Center, 1600 Divisadero Street, 4th Floor, Box 1705, San Francisco, CA 94115, USA.
Cancer Chemother Pharmacol. 2010 Nov;66(6):1051-7. doi: 10.1007/s00280-010-1257-5. Epub 2010 Feb 4.
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 ≥25% 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.
在一线化疗进展后，转移性胰腺癌患者尚无标准治疗方法。基于同时抑制 VEGF 和 EGFR 的潜在附加或协同作用，我们进行了一项 II 期研究，评估贝伐珠单抗联合厄洛替尼在这一患者人群中的疗效。
符合条件的患者为转移性胰腺腺癌，ECOG 体能状态 0-1，并且先前接受过 1-3 种全身治疗（至少一种基于吉西他滨）。治疗方案为贝伐珠单抗 15mg/kg 每 21 天一次联合厄洛替尼 150mg 每日一次。
共入组 36 例患者，其中 8 例患者先前接受过 VEGF 靶向治疗，9 例患者先前接受过厄洛替尼治疗。中位治疗周期数为 2 个（范围，1-7 个）。常见的毒性包括皮疹（72%）、腹泻（25%）、静脉血栓栓塞事件（15%）和高血压（11%）。1 例患者有部分缓解，7 例患者疾病稳定超过 2 个周期。26 例基线 CA19-9 水平>2x ULN 的患者中，有 4 例下降≥25%。中位无进展生存期为 40 天（95%CI，35-41 天），中位总生存期为 102 天（95%CI，74-117 天），6 个月生存率为 22%。循环内皮细胞（CD45(-)/CD34(+)/CD31(+））基线浓度与总生存期呈负相关。
贝伐珠单抗联合厄洛替尼治疗吉西他滨耐药转移性胰腺癌安全但疗效相对较差。未来的研究应集中于确定这一具有挑战性的患者人群中可能从一线治疗以外获益的亚组。
