Tamiya Akihiro, Tamiya Motohiro, Shiroyama Takayuki, Saijo Nobuhiko, Nakatani Takeshi, Minomo Shojiro, Tsuji Taisuke, Takeuchi Naoko, Omachi Naoki, Kurata Kanako, Suzuki Hidekazu, Okamoto Norio, Okishio Kyoichi, Hirashima Tomonori, Atagi Shinji
Department of Internal Medicine, Kinki-Chuo Chest Medical Center, Osaka, Japan.
Med Oncol. 2015 Mar;32(3):40. doi: 10.1007/s12032-014-0474-x. Epub 2015 Jan 25.
Gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), is an effective treatment for advanced non-small cell lung cancer (NSCLC) in patients with activating EGFR mutations. However, there have been little evidence-based studies of gefitinib in combination with platinum-doublet therapy in these patients. We performed a phase II trial to determine the efficacy and safety of triplet chemotherapy with gefitinib, carboplatin, and S-1 as a first-line treatment. This was a multicentre, single-arm, phase II trial of carboplatin, S-1, and gefitinib in advanced NSCLC patients with activating EGFR mutations. Patients received four courses of these drugs in 3-4 week cycles. In each cycle, carboplatin (area under curve = 5) was administered on day 1, S-1 (80 mg/m(2)) on days 1-14, and gefitinib (250 mg) every day. Subsequently, the same regimen without carboplatin was administered until disease progression or unacceptable toxicity occurred. The 1-year progression-free survival (PFS) was the primary endpoint, while response rate (RR), PFS, overall survival (OS), and safety were secondary endpoints. Thirty-five patients were enrolled into this study. The 1-year PFS was 74.3% and the overall RR was 85.7%. The median PFS for all patients was 17.6 months (95% confidence interval 15.5-∞), but the median OS was not reached, because 28 patients were still alive after a median follow-up time of 21.4 months. Haematological adverse events (grade 3 or higher) included neutropaenia (17.1%), thrombocytopenia (14.3%), and anaemia (5.7%), while non-haematological adverse events (grade 3 or higher) included elevated aminotransferase (20.0%), diarrhoea (14.3%), and febrile neutropaenia (2.9%). No interstitial lung disease or treatment-related deaths occurred. Combination chemotherapy with carboplatin, S-1, and gefitinib is efficacious and well tolerated as a first-line treatment in advanced NSCLC patients with activating EGFR mutations.
吉非替尼是一种表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI），对具有EGFR激活突变的晚期非小细胞肺癌（NSCLC）患者是一种有效的治疗方法。然而，关于吉非替尼联合铂类双药疗法用于这些患者的循证研究很少。我们进行了一项II期试验，以确定吉非替尼、卡铂和S-1三联化疗作为一线治疗的疗效和安全性。这是一项针对具有EGFR激活突变的晚期NSCLC患者的多中心、单臂II期试验，采用卡铂、S-1和吉非替尼治疗。患者每3-4周接受四个疗程的这些药物治疗。在每个周期中，卡铂（曲线下面积=5）于第1天给药，S-1（80mg/m²）于第1-14天给药，吉非替尼（250mg）每日给药。随后，给予相同方案但不含卡铂的治疗，直至疾病进展或出现不可接受的毒性。1年无进展生存期（PFS）是主要终点，而缓解率（RR）、PFS、总生存期（OS）和安全性是次要终点。35例患者入组本研究。1年PFS为74.3%，总RR为85.7%。所有患者的中位PFS为17.6个月（95%置信区间15.5-∞），但中位OS未达到，因为在中位随访时间21.4个月后仍有28例患者存活。血液学不良事件（3级或更高）包括中性粒细胞减少（17.1%）、血小板减少（14.3%）和贫血（5.7%），而非血液学不良事件（3级或更高）包括转氨酶升高（20.0%）、腹泻（14.3%）和发热性中性粒细胞减少（2.9%）。未发生间质性肺病或与治疗相关的死亡。卡铂、S-1和吉非替尼联合化疗作为具有EGFR激活突变的晚期NSCLC患者的一线治疗有效且耐受性良好。
