- 作者：Isamu Okamoto ; Koji Takeda ; Haruko Daga ; Masaki Miyazaki ; Kimio Yonesaka ; Hidemi Kiyota ; Junji Tsurutani ; Shinya Ueda ; Yasuko Ichikawa ; Masayuki Takeda ; Risa Sekiguchi ; Kiyomi Tominaga ; Sotaro Enatsu
- 关键词：Pemetrexed ; Carboplatin ; Dose-escalation ; First-line therapy ; Maintenance therapy ; NSCLC
- 刊名：Lung Cancer
- 出版年：2010
- 出版时间：November 2010
- 年：2010
- 卷：70
- 期：2
- 页码：168-173
- 全文大小：117 K
IntroductionThe primary objectives of this study were to determine the recommended dose of pemetrexed and carboplatin in patients with chemo-naive advanced non-small cell lung cancer (NSCLC).Methods
Patients received escalated doses of carboplatin area under the concentration–time curve (AUC) of 5 (cohort 1) or 6 (cohort 2) and pemetrexed 500 mg/m2 every 3 weeks for six cycles. For patients with objective response and stable disease, pemetrexed were continued until disease progression or unacceptable toxicity.
Results
In cohort 1, a dose-limiting toxicity (DLT) was observed in one of the six patients: grade 4 thrombocytopenia. No DLTs were seen in the first 6 patients of cohort 2, and thus the combination of pemetrexed 500 mg/m2 plus carboplatin at AUC 6 was determined as the recommended dose. Among a total of 20 patients, 8 patients received a median of four cycles of pemetrexed monotherapy in a maintenance setting without unexpected or cumulative toxicities. No complete responses and 12 partial responses were observed, giving an overall response rate of 60.0 % [95 % confidence interval (CI), 36.1–80.9 % ]. Median progression-free survival time for all patients was 7.6 months (95 % CI: 4.8–8.0 months).
Conclusions
Pemetrexed 500 mg/m2 plus carboplatin AUC 6 combination therapy followed by pemetrexed maintenance therapy, is generally tolerable, and shows encouraging antitumor activity in chemotherapy-naive patients with advanced NSCLC.