Division of hematology/oncology, Department of medicine, University of New Mexico Comprehensive Cancer Center, Albuquerque, New Mexico.
University of California Riverside and Kaiser Permanente Riverside, Moreno valley, California.
Cancer Med. 2017 Sep;6(9):2042-2051. doi: 10.1002/cam4.1138. Epub 2017 Aug 11.
Hepatocellular Carcinoma (HCC) incidence is increasing in the USA. Gemcitabine (G) and oxaliplatin (O) are active in HCC and biliary duct cancer (BDC). Erlotinib (E) is an EGFR tyrosine kinase inhibitor (TKI) with known activity against both. We sought to evaluate the efficacy of the combination G+O+E. Patients with either of the two diagnosis were treated in a phase II trial. Simons 2 stage design was used. A disease-control rate (DCR), complete response (CR) + partial response (PR)+ stable disease (SD) at 24 weeks of ≤20% and >40% (P0 and P1 of 0.2 and 0.4, respectively) were set as undesirable (null) and desirable results. 26 HCC and 7 BDC patients were accrued. In HCC, 1 PR, 10 SD, and 9 PDs were seen. DCR in HCC was 42%. Among seven (7) patients with BDC, one patient was not evaluable; one achieved a long lasting PR, and five patients had SD and DCR was 86%. Median overall survival (OS) times and progression-free survivals (PFS) were 196 and 149 days in HCC and 238 days and not reached in BDC. PFS at 26 weeks in HCC was 41% and at 21 weeks in BDC was 60%. Grade 3 toxicities in >5% of patients were fatigue (12.9%), neutropenia (9.6%), thrombocytopenia (9.6%), and diarrhea (6.4%). G+O+E exceeded both preset P0a and P1 of the primary objective with a PFS of 41% at 26 weeks for HCC and preliminary BDC data may warrant further investigations.
原发性肝癌（HCC）在美国的发病率正在上升。吉西他滨（G）和奥沙利铂（O）在 HCC 和胆管癌（BDC）中具有活性。厄洛替尼（E）是一种表皮生长因子受体酪氨酸激酶抑制剂（TKI），对两者均有已知的活性。我们试图评估 G+O+E 联合治疗的疗效。两种诊断中的任何一种的患者都在一项 II 期试验中接受治疗。采用西蒙两阶段设计。设定疾病控制率（DCR），即 24 周时≤20%和>40%的完全缓解（CR）+部分缓解（PR）+稳定疾病（SD）（P0 和 P1 分别为 0.2 和 0.4）为不理想（无效）和理想结果。共入组 26 例 HCC 和 7 例 BDC 患者。在 HCC 中，观察到 1 例 PR、10 例 SD 和 9 例 PD。HCC 的 DCR 为 42%。在 7 例 BDC 患者中，1 例不可评价；1 例获得持久的 PR，5 例 SD，DCR 为 86%。HCC 的中位总生存期（OS）和无进展生存期（PFS）分别为 196 和 149 天，BDC 为 238 天和未达到。HCC 患者 26 周时的 PFS 为 41%，BDC 患者 21 周时的 PFS 为 60%。>5%的患者发生 3 级毒性的有疲劳（12.9%）、中性粒细胞减少（9.6%）、血小板减少（9.6%）和腹泻（6.4%）。G+O+E 超过了主要目标的预设 P0a 和 P1，HCC 的 26 周 PFS 为 41%，BDC 的初步数据可能需要进一步研究。
