Kubo Emi, Yamamoto Noboru, Nokihara Hiroshi, Fujiwara Yutaka, Horinouchi Hidehito, Kanda Shintaro, Goto Yasushi, Ohe Yuichiro
Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan.
Mol Clin Oncol. 2017 Jan;6(1):56-62. doi: 10.3892/mco.2016.1076. Epub 2016 Nov 9.
The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor gefitinib was initially approved in Japan in 2002 for the treatment of advanced or metastatic non-small-cell lung cancer (NSCLC); however, the optimal order of conventional cytotoxic chemotherapy (carboplatin and paclitaxel) and gefitinib administration has not been determined. We conducted a randomized phase II study of carboplatin and paclitaxel followed by gefitinib vs. gefitinib followed by carboplatin and paclitaxel to select a candidate for further development in a phase III study of chemotherapy-naïve patients with advanced or metastatic NSCLC, regardless of their mutation status. A total of 97 patients meeting this description were randomly assigned to arm A (carboplatin and paclitaxel followed by gefitinib; n=49) or B (gefitinib followed by carboplatin and paclitaxel; n=48) from June, 2003 to October, 2005. Carboplatin and paclitaxel were administered in 4 cycles every 3 weeks; gefitinib was continued until disease progression or development of unacceptable toxicity. The primary endpoint was overall survival; the secondary endpoints were response rate and adverse event prevalence. The median overall follow-up was 65.1 months (range, 28.7-75.1 months). The major toxicities were hematological (carboplatin and paclitaxel) or skin rash, diarrhea and hepatic dysfunction (gefitinib). Interstitial lung disease was observed in 1 patient from each arm. In arms A and B, the carboplatin and paclitaxel response rate, gefitinib response rate, and median survival durations were 34.8 and 26.5%, 33.3 and 35.7%, and 18.8 and 17.2 months, respectively. Arm A was selected for a subsequent phase III study.
表皮生长因子受体（EGFR）酪氨酸激酶抑制剂吉非替尼于2002年在日本首次获批用于治疗晚期或转移性非小细胞肺癌（NSCLC）；然而，传统细胞毒性化疗（卡铂和紫杉醇）与吉非替尼给药的最佳顺序尚未确定。我们进行了一项随机II期研究，比较卡铂和紫杉醇序贯吉非替尼与吉非替尼序贯卡铂和紫杉醇，以选择在晚期或转移性NSCLC初治患者的III期研究中进一步开发的候选方案，无论其突变状态如何。2003年6月至2005年10月，共有97例符合该描述的患者被随机分配至A组（卡铂和紫杉醇序贯吉非替尼；n = 49）或B组（吉非替尼序贯卡铂和紫杉醇；n = 48）。卡铂和紫杉醇每3周进行4个周期给药；吉非替尼持续使用直至疾病进展或出现不可接受的毒性。主要终点为总生存期；次要终点为缓解率和不良事件发生率。中位总随访时间为65.1个月（范围：28.7 - 75.1个月）。主要毒性为血液学毒性（卡铂和紫杉醇）或皮疹、腹泻和肝功能障碍（吉非替尼）。每组均有1例患者出现间质性肺病。在A组和B组中，卡铂和紫杉醇的缓解率、吉非替尼的缓解率以及中位生存期分别为34.8%和26.5%、33.3%和35.7%、18.8个月和17.2个月。A组被选入后续的III期研究。
