Rocha Lima Caio M, Lin Edward H, Kim George P, Giguere Jeffrey K, Marshall John, Zalupski Mark, Papageorgio Chris, Auber Miklos L, Kaleta Remigiusz, McHenry M Brent, Trifan Ovidiu C, Philip Philip A
University of Miami Sylvester Comprehensive Cancer Center Miami, FL.
Gastrointest Cancer Res. 2012 Sep;5(5):155-60.
The aim of this phase 2 study was to evaluate the safety and efficacy of ixabepilone plus cetuximab in patients with advanced pancreatic cancer.
Eligible patients had advanced pancreatic adenocarcinoma that was metastatic or not amenable to resection, a Karnofsky performance status ≥70%, and no prior therapy for advanced disease. Patients received ixabepilone 32 mg/m(2) (3-hour IV infusion) every 3 weeks and cetuximab 250 mg/m(2) (1-hour IV infusion) weekly. The primary efficacy end point was the 6-month survival rate. Secondary end points included tumor response rate, overall survival, progression-free survival, and tolerability.
A total of 54 patients were enrolled on this study. The 6-month survival rate was 57% (31/54: 95% CI: 43-71%) with a median overall survival of 7.6 months (95% CI: 5.5-12.2 months). Patients who developed acneiform rash (n = 36) had a median survival of 8.8 months, compared with 2.6 months for those without rash (n = 18). Of 31 patients with measurable disease (defined as response-evaluable), 4 had confirmed partial responses and an additional 24 had stable disease. The combination was generally well-tolerated with the most common grade 3/4 hematological toxicities being leucopenia (39%) and neutropenia (33%). The most common grade 3/4 nonhematologic toxicity was fatigue (17%).
The combination of ixabepilone and cetuximab was active and had acceptable toxicity. The efficacy results are similar to single-agent ixabepilone and gemcitabine-based combination therapies in patients with advanced pancreatic cancer. Exploratory analyses suggest a trend toward improved survival for patients who experienced rash.
本2期研究旨在评估伊沙匹隆联合西妥昔单抗治疗晚期胰腺癌患者的安全性和疗效。
符合条件的患者患有转移性或不可切除的晚期胰腺腺癌，卡氏评分≥70%，且既往未接受过晚期疾病治疗。患者每3周接受一次伊沙匹隆32 mg/m²（静脉输注3小时），每周接受一次西妥昔单抗250 mg/m²（静脉输注1小时）。主要疗效终点为6个月生存率。次要终点包括肿瘤缓解率、总生存期、无进展生存期和耐受性。
本研究共纳入54例患者。6个月生存率为57%（31/54：95%置信区间：43 - 71%），中位总生存期为7.6个月（95%置信区间：5.5 - 12.2个月）。出现痤疮样皮疹的患者（n = 36）中位生存期为8.8个月，未出现皮疹的患者（n = 18）中位生存期为2.6个月。在31例可测量疾病（定义为可评估缓解情况）的患者中，4例确认部分缓解，另外24例病情稳定。该联合治疗总体耐受性良好，最常见的3/4级血液学毒性为白细胞减少（39%）和中性粒细胞减少（33%）。最常见的3/4级非血液学毒性为疲劳（17%）。
伊沙匹隆和西妥昔单抗联合治疗具有活性且毒性可接受。疗效结果与伊沙匹隆单药及基于吉西他滨的联合治疗方案在晚期胰腺癌患者中的疗效相似。探索性分析表明，出现皮疹的患者有生存改善的趋势。
