TY - JOUR
T1 - Dose-escalation study of pemetrexed in combination with carboplatin followed by pemetrexed maintenance therapy for advanced non-small cell lung cancer
AU - Okamoto, Isamu
AU - Takeda, Koji
AU - Daga, Haruko
AU - Miyazaki, Masaki
AU - Yonesaka, Kimio
AU - Kiyota, Hidemi
AU - Tsurutani, Junji
AU - Ueda, Shinya
AU - Ichikawa, Yasuko
AU - Takeda, Masayuki
AU - Sekiguchi, Risa
AU - Tominaga, Kiyomi
AU - Enatsu, Sotaro
AU - Nambu, Yoshihiro
AU - Nakagawa, Kazuhiko
N1 - Funding Information:
The study was sponsored and supported by Eli Lilly Japan K.K .
PY - 2010/11
Y1 - 2010/11
N2 - Introduction: The 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 500mg/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 500mg/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 500mg/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.
AB - Introduction: The 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 500mg/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 500mg/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 500mg/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.
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U2 - 10.1016/j.lungcan.2010.02.007
DO - 10.1016/j.lungcan.2010.02.007
M3 - Article
C2 - 20236726
AN - SCOPUS:77957017091
SN - 0169-5002
VL - 70
SP - 168
EP - 173
JO - Lung Cancer
JF - Lung Cancer
IS - 2
ER -
