Suzuki Ryujiro, Yamamoto Masashi, Saka Hideo, Taniguchi Hiroyuki, Shindoh Joe, Tanikawa Yoshimasa, Nomura Fumio, Gonda Hideo, Imaizumi Kazuyoshi, Hasegawa Yoshinori, Shimokata Kaoru
Division of Respiratory Medicine, Toyohashi Municipal Hospital, 50 Hachiken-nishi, Aotake, Toyohashi, Aichi 441-8570, Japan.
Lung Cancer. 2009 Jan;63(1):72-6. doi: 10.1016/j.lungcan.2008.04.002. Epub 2008 May 21.
Cyclooxygenase (COX-2) overexpression is seen in many malignancies including lung cancer. Recent pre-clinical studies have shown that selective COX-2 inhibitors have demonstrated promising results when used with chemotherapy. Based on these observations, we assessed the efficacy and tolerability of the combination chemotherapy consisting of carboplatin and paclitaxel with meloxicam, a selective COX-2 inhibitor.
Forty-four patients with stage IIIB or IV non-small cell lung cancer (NSCLC), Eastern Cooperative Oncology Group performance status (PS) 0 or 1, who had adequate organ function, were eligible. Patients received paclitaxel 70 mg/m(2) weekly for 3 of 4 weeks with carbopltin (AUC 6) on day 1, as well as daily meloxicam (10 mg/day). The response rate was the primary endpoint. Secondary endpoints were overall survival, toxicity profile and quality of life (using European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and LC13).
From March 2005 to September 2006, 44 patients were evaluated in this study. Gender M/F, 31/13; median age, 64 years (range, 34-75); stage IIIB/IV, 11/33; PS0/1, 22/22; histology Ad/Sq/Other, 29/6/9. Partial response was observed in 19 patients (43%) with stable disease, and there was no complete response, for an overall response rate of 43% (95% confidence interval, 28.5-57.8%). Ten patients (23%) had grade (G) 3 and three (7%) had G4 neutropenia. Three patients (7%) had G3 thrombocytopenia. As for non-hematological toxicities, one case of G4 toxicity (perforation of jejunum) was observed, but other toxicities were mild (one muscle pain, two liver dysfunction, one fatigue and one nausea G3). Grade 2 peripheral neuropathy was observed in only one patient. Using the EORTC QLQ questionnaire, the global health status did not change significantly during this therapy (before and 4 and 8 weeks later). Median follow-up was 13.6 months (range, 1.8-31.3 months). By the time of the final analysis (October 2007), 26 of the initial 44 patients had died. The 1-year survival rate was 64% and median survival time was 15.9 months.
Meloxicam in combination with carboplatin and weekly paclitaxel chemotherapy showed promising activity with encouraging survival. This therapy is relatively well tolerated in advanced NSCLC.
环氧化酶（COX-2）在包括肺癌在内的许多恶性肿瘤中均有过表达。近期临床前研究表明，选择性COX-2抑制剂与化疗联合使用时已显示出有前景的结果。基于这些观察结果，我们评估了卡铂和紫杉醇联合选择性COX-2抑制剂美洛昔康的联合化疗的疗效和耐受性。
44例ⅢB期或Ⅳ期非小细胞肺癌（NSCLC）患者符合条件，这些患者东部肿瘤协作组（ECOG）体能状态（PS）为0或1，且器官功能良好。患者在第1天接受卡铂（AUC 6），并在4周中的3周每周接受紫杉醇70mg/m²，同时每日服用美洛昔康（10mg/天）。缓解率是主要终点。次要终点包括总生存期、毒性特征和生活质量（使用欧洲癌症研究与治疗组织（EORTC）QLQ-C30和LC13量表）。
从2005年3月至2006年9月，本研究评估了44例患者。性别男/女为31/13；中位年龄64岁（范围34 - 75岁）；ⅢB/Ⅳ期为11/33；PS0/1为22/22；组织学类型腺癌/鳞癌/其他为29/6/9。19例患者（43%）观察到部分缓解，疾病稳定，无完全缓解，总缓解率为43%（95%置信区间，28.5 - 57.8%）。10例患者（23%）出现3级（G）中性粒细胞减少，3例（7%）出现4级中性粒细胞减少。3例患者（7%）出现3级血小板减少。至于非血液学毒性，观察到1例4级毒性（空肠穿孔），但其他毒性较轻（1例肌肉疼痛、2例肝功能障碍、1例疲劳和1例3级恶心）。仅1例患者观察到2级周围神经病变。使用EORTC QLQ问卷，在此治疗期间（治疗前、4周和8周后）总体健康状况无显著变化。中位随访时间为13.6个月（范围1.8 - 31.3个月）。到最终分析时（2007年10月），最初44例患者中有26例死亡。1年生存率为64%，中位生存时间为15.9个月。
美洛昔康联合卡铂和每周一次的紫杉醇化疗显示出有前景的活性和令人鼓舞的生存期。这种治疗在晚期NSCLC中耐受性相对良好。
