Brell Joanna M, Matin Khalid, Evans Terry, Volkin Robert L, Kiefer Gauri J, Schlesselman James J, Dranko Shelley, Rath Linda, Schmotzer Amy, Lenzner Diana, Ramanathan Ramesh K
University Hospitals Case Medical Center, Ireland Cancer Center, Cleveland, Ohio, USA.
Oncology. 2009;76(4):270-4. doi: 10.1159/000206141. Epub 2009 Mar 4.
There is no standard second-line therapy for advanced pancreatic cancer (APC). We evaluated the epidermal growth factor receptor (EGFR) inhibitor gefitinib and docetaxel in a phase II study following gemcitabine failure.
EGFR overexpression was not required. The initial docetaxel dose was 75 mg/m(2) on day 1 every 21 days. Due to febrile neutropenia in 8 of the first 18 patients, the dose was reduced to 60 mg/m(2). Gefitinib, 250 mg/day orally, was given continuously.
Forty-one patients received treatment and were evaluable. Febrile neutropenia was seen in 11 patients (27%), with most events occurring at the docetaxel dose of 75 mg/m(2) (8 of 18 patients). Common treatment-related grade 3/4 toxicities were: fatigue (7%), nausea (7%), diarrhea (5%) and vomiting (2%). There was 1 partial response and stable disease in 19 patients. Time to progression was 1.8 months and median survival was 4.5 months (95% CI 2.9-5.7).
The tolerability and feasibility of second-line therapy for APC was demonstrated. The combination of gefitinib and docetaxel showed evidence of limited efficacy.
晚期胰腺癌（APC）尚无标准的二线治疗方案。我们在一项吉西他滨治疗失败后的II期研究中评估了表皮生长因子受体（EGFR）抑制剂吉非替尼和多西他赛。
无需EGFR过表达。初始多西他赛剂量为每21天第1天75mg/m²。由于前18例患者中有8例出现发热性中性粒细胞减少，剂量减至60mg/m²。吉非替尼每日口服250mg，持续给药。
41例患者接受治疗并可评估。11例患者（27%）出现发热性中性粒细胞减少，大多数事件发生在多西他赛剂量为75mg/m²时（18例患者中的8例）。常见的3/4级治疗相关毒性为：疲劳（7%）、恶心（7%）、腹泻（5%）和呕吐（2%）。有1例部分缓解，19例患者病情稳定。疾病进展时间为1.8个月，中位生存期为4.5个月（95%CI 2.9 - 5.7）。
证明了APC二线治疗的耐受性和可行性。吉非替尼和多西他赛联合显示出疗效有限的证据。
