Dept of Radiation Oncology, Unit 97, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX.
J Clin Oncol. 2011 Aug 1;29(22):3037-43. doi: 10.1200/JCO.2010.33.8038. Epub 2011 Jun 27.
This phase II trial was designed to assess the efficacy and safety of cetuximab, gemcitabine, and oxaliplatin followed by cetuximab, capecitabine, and radiation therapy in locally advanced pancreatic cancer (LAPC).
Treatment-naive eligible patients (n = 69) received intravenous gemcitabine (1,000 mg/m(2)) and oxaliplatin (100 mg/m(2)) every 2 weeks for four doses, followed by radiation (50.4 Gy to the gross tumor only) with concurrent capecitabine (825 mg/m(2) twice daily on radiation treatment days). Cetuximab (500 mg/m(2)) was started on day 1 of chemotherapy and was continued every 2 weeks during chemotherapy and chemoradiotherapy. Diagnostic cytology specimens were immunostained for Smad4(Dpc4) expression.
Median overall survival time was 19.2 months (95% CI, 14.2 to 24.2 months), and 1-year, 2-year, and 4-year actuarial overall survival rates were 66.0%, 25.02%, and 11.3%, respectively. Acneiform rash correlated with improved survival (P = .001), but initial CA19-9, borderline resectable initial stage, and surgical resection (n = 7) did not. The 1-year and 2-year radiographic local progression rates were 22.8% and 61.0%, respectively. The worst acute toxic effects were GI toxicity (32% and 10% for grades 2 and 3, respectively); fatigue (26% and 6% for grades 2 and 3, respectively); sensory neuropathy (9% and 1% for grades 2 and 3, respectively); and acneiform rash (54% and 3% for grades 2 and 3, respectively). Smad4(Dpc4) expression correlated with a local rather than a distant dominant pattern of disease progression (P = .016).
This regimen appears effective and has acceptable toxicity. The primary end point (1-year overall survival rate > 45%) was met, with encouraging survival duration. Smad4(Dpc4) immunostaining correlated with the pattern of disease progression. Prospective validation of Smad4(Dpc4) expression in cytology specimens as a predictive biomarker is warranted and may lead to personalized treatment strategies for patients with localized pancreatic cancer.
本Ⅱ期临床试验旨在评估西妥昔单抗、吉西他滨和奥沙利铂联合治疗后序贯西妥昔单抗、卡培他滨和放疗在局部晚期胰腺癌（LAPC）中的疗效和安全性。
符合条件的初治患者（n=69）接受静脉注射吉西他滨（1000mg/m2）和奥沙利铂（100mg/m2）每 2 周 4 个剂量，随后进行放疗（仅对大体肿瘤给予 50.4Gy），同时给予卡培他滨（825mg/m2，每天 2 次，在放疗日给予）。西妥昔单抗（500mg/m2）于化疗第 1 天开始，并在化疗和放化疗期间每 2 周继续使用。诊断细胞学标本进行 Smad4（Dpc4）表达的免疫染色。
中位总生存时间为 19.2 个月（95%CI，14.2 至 24.2 个月），1 年、2 年和 4 年的总生存率分别为 66.0%、25.02%和 11.3%。痤疮样皮疹与生存改善相关（P=0.001），但初始 CA19-9、边界可切除的初始分期和手术切除（n=7）则无相关性。1 年和 2 年的放射性局部进展率分别为 22.8%和 61.0%。最严重的急性毒性作用是胃肠道毒性（分别为 2 级和 3 级 32%和 10%）；疲劳（分别为 2 级和 3 级 26%和 6%）；感觉神经病变（分别为 2 级和 3 级 9%和 1%）；和痤疮样皮疹（分别为 2 级和 3 级 54%和 3%）。Smad4（Dpc4）表达与局部而非远处疾病进展模式相关（P=0.016）。
该方案似乎有效且毒性可接受。主要终点（1 年总生存率>45%）得到满足，且生存时间令人鼓舞。Smad4（Dpc4）免疫染色与疾病进展模式相关。需要对细胞学标本中 Smad4（Dpc4）表达作为预测生物标志物进行前瞻性验证，这可能为局部胰腺癌患者带来个体化治疗策略。
