Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland 21231, USA.
Int J Radiat Oncol Biol Phys. 2013 Jul 15;86(4):678-85. doi: 10.1016/j.ijrobp.2013.03.032.
Long-term survival rates for patients with resected pancreatic ductal adenocarcinoma (PDAC) have stagnated at 20% for more than a decade, demonstrating the need to develop novel adjuvant therapies. Gemcitabine-erlotinib therapy has demonstrated a survival benefit for patients with metastatic PDAC. Here we report the first phase 2 study of erlotinib in combination with adjuvant chemoradiation and chemotherapy for resected PDAC.
Forty-eight patients with resected PDAC received adjuvant erlotinib (100 mg daily) and capecitabine (800 mg/m(2) twice daily Monday-Friday) concurrently with intensity modulated radiation therapy (IMRT), 50.4 Gy over 28 fractions followed by 4 cycles of gemcitabine (1000 mg/m(2) on days 1, 8, and 15 every 28 days) and erlotinib (100 mg daily). The primary endpoint was recurrence-free survival (RFS).
The median follow-up time was 18.2 months (interquartile range, 13.8-27.1). Lymph nodes were positive in 85% of patients, and margins were positive in 17%. The median RFS was 15.6 months (95% confidence interval [CI], 13.4-17.9), and the median overall survival (OS) was 24.4 months (95% CI, 18.9-29.7). Multivariate analysis with adjustment for known prognostic factors showed that tumor diameter >3 cm was predictive for inferior RFS (hazard ratio, 4.01; P=.001) and OS (HR, 4.98; P=.02), and the development of dermatitis was associated with improved RFS (HR, 0.27; P=.009). During CRT and post-CRT chemotherapy, the rates of grade 3/4 toxicity were 31%/2% and 35%/8%, respectively.
Erlotinib can be safely administered with adjuvant IMRT-based CRT and chemotherapy. The efficacy of this regimen appears comparable to that of existing adjuvant regimens. Radiation Therapy Oncology Group 0848 will ultimately determine whether erlotinib produces a survival benefit in patients with resected pancreatic cancer.
在过去的十年中，接受手术切除的胰腺导管腺癌（PDAC）患者的长期生存率一直停滞在 20%，这表明需要开发新的辅助疗法。吉西他滨联合厄洛替尼治疗转移性 PDAC 已显示出生存获益。在此，我们报告了首例在接受手术切除的 PDAC 患者中进行的厄洛替尼联合辅助放化疗的 2 期研究。
48 例接受手术切除的 PDAC 患者接受辅助厄洛替尼（每天 100mg）和卡培他滨（每天两次，每次 800mg/m2，周一至周五）联合强度调制放射治疗（IMRT），50.4Gy 共 28 个分次，随后接受 4 个周期的吉西他滨（1000mg/m2，每 28 天第 1、8 和 15 天）和厄洛替尼（每天 100mg）治疗。主要终点为无复发生存率（RFS）。
中位随访时间为 18.2 个月（四分位距，13.8-27.1）。85%的患者淋巴结阳性，17%的患者切缘阳性。中位 RFS 为 15.6 个月（95%置信区间，13.4-17.9），中位总生存期（OS）为 24.4 个月（95%置信区间，18.9-29.7）。多变量分析调整已知预后因素后显示，肿瘤直径>3cm 与 RFS 降低（风险比，4.01；P=.001）和 OS 降低（HR，4.98；P=.02）相关，而皮疹的发生与 RFS 改善相关（HR，0.27；P=.009）。在 CRT 和 CRT 后化疗期间，3 级/4 级毒性发生率分别为 31%/2%和 35%/8%。
厄洛替尼可安全地与辅助基于 IMRT 的 CRT 和化疗联合使用。该方案的疗效似乎与现有辅助方案相当。放射治疗肿瘤学组 0848 将最终确定厄洛替尼是否能为接受手术切除的胰腺癌患者带来生存获益。
