Tachihara Motoko, Kiriu Tatsunori, Hata Akito, Hatakeyama Yukihisa, Nakata Kyosuke, Nagano Tatsuya, Yamamoto Masatsugu, Kobayashi Kazuyuki, Ohnishi Hisashi, Katakami Nobuyuki, Nishimura Yoshihiro
Division of Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo 650-0017, Japan.
Department of Medical Oncology, Kobe City Medical Center General Hospital, Kobe, Hyogo 650-0047, Japan.
Cancer Manag Res. 2019 Jul 29;11:7135-7140. doi: 10.2147/CMAR.S208224. eCollection 2019.
Nanoparticle albumin-bound paclitaxel (nab-PTX) plus gemcitabine (GEM) significantly improved overall survival in patients with metastatic pancreatic adenocarcinoma. Anti-tumor synergy between GEM and nab-PTX was recently demonstrated in a mouse model. We planned to assess the efficacy and safety of the combination of nab-PTX + GEM in patients with non-small-cell lung cancer (NSCLC) previously treated with platinum-based chemotherapy.
Patients with advanced NSCLC with progressive disease after platinum-based chemotherapy, an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1, and adequate kidney, liver and bone marrow function were eligible. Treatment consisted of nab-PTX (100 mg/m) + GEM (1000 mg/m) on days 1 and 8 of each 3-week cycle until progression disease or unacceptable toxicity occurred. The primary endpoint was progression-free survival (PFS).
Of the 28 patients enrolled, all were evaluable for response and toxicity. The median age was 68 years (range 47-79), and 23 were male and 5 female. The histologic subtypes were: adenocarcinoma in 19 patients, and squamous cell carcinoma in 9 patients. Seventeen patients had ECOG PS 1 and 11 patients had PS 0. Twenty-four patients were second line and 4 patients were third line. The median number of cycles administered was 4 (range 1-10). The overall response rate was 17.9%. The disease control rate was 67.9%. The median progression-free survival was 3.1 months (95% confidence interval [CI] =1.6-4.1). Adverse events were generally tolerable except grade 3 interstitial pneumonia with in 4 patients (14.3%).
The efficacy of nab-PTX in combination with GEM in advanced second or third-line NSCLC patients was limited and the frequent occurrence of interstitial pneumonia was unacceptable.
纳米白蛋白结合型紫杉醇（nab-PTX）联合吉西他滨（GEM）显著改善了转移性胰腺腺癌患者的总生存期。最近在小鼠模型中证实了GEM与nab-PTX之间的抗肿瘤协同作用。我们计划评估nab-PTX + GEM联合方案在先前接受铂类化疗的非小细胞肺癌（NSCLC）患者中的疗效和安全性。
符合条件的患者为铂类化疗后疾病进展的晚期NSCLC患者，东部肿瘤协作组（ECOG）体能状态（PS）为0或1，且肾、肝和骨髓功能良好。治疗方案为每3周周期的第1天和第8天给予nab-PTX（100 mg/m²）+ GEM（1000 mg/m²），直至疾病进展或出现不可接受的毒性。主要终点为无进展生存期（PFS）。
入组的28例患者均可评估疗效和毒性。中位年龄为68岁（范围47 - 79岁），男性23例，女性5例。组织学亚型为：腺癌19例，鳞状细胞癌9例。17例患者ECOG PS为1，11例患者PS为0。24例患者为二线治疗，4例患者为三线治疗。中位给药周期数为4（范围1 - 10）。总缓解率为17.9%。疾病控制率为67.9%。中位无进展生存期为3.1个月（95%置信区间[CI]=1.6 - 4.1）。不良事件一般可耐受，但4例患者（14.3%）出现3级间质性肺炎。
nab-PTX联合GEM在晚期二线或三线NSCLC患者中的疗效有限，且间质性肺炎频繁发生难以接受。
