Dose-escalation study of pemetrexed in combination with carboplatin followed by pemetrexed maintenance therapy for advanced non-small cell lung cancer
Received 26 December 2009; received in revised form 16 February 2010; accepted 18 February 2010. published online 17 March 2010. Corrected Proof
Abstract
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.
ABSTRACT
mg/m