Combination chemotherapy of intermittent erlotinib with pemetrexed for pretreated patients with advanced non-small cell lung cancer: A phase I dose-finding study.

Abstract

e18056 Background: Erlotinib and pemetrexed have been approved in second-line treatment for non-small cell lung cancer (NSCLC) and have different mechanisms of action. Their combination could potentially augment the antitumor activity brought by either agent alone. We investigated the safety in combination of erlotinib and pemetrexed in pretreated NSCLC patients. Methods: A phase I dose-finding study was performed in patients with stage III/IV nonsquamous NSCLC whose disease had progressed on or after receiving first-line chemotherapy. This study was registered as UMIN000002900. Patients received 500 mg/m2 of pemetrexed intravenously every 21 days and erlotinib (100 mg in Level 1, 150 mg in Level 2) orally on days 2-16. Results: Twelve patients were recruited. Patient characteristics included median age of 66 (range, 48-78), 9 males, 9 stage IV, 7 adenocarcinoma, and 2 activating mutation-positives in the gene of epidermal growth factor receptor. Treatment was well-tolerated and the recommended dose of erlotinib was fixed on 150 mg. Dose-limiting toxicities were experienced in 3 patients: grade 3 elevation of serum alanine aminotransferase, repetitive grade 4 neutropenia that required the second dose reduction of pemetrexed, and grade 3 diarrhea. None experienced drug-induced interstitial lung disease. Three patients achieved partial response and 5 kept stable disease. Conclusions: Combination chemotherapy of intermittent erlotinib with pemetrexed was well-tolerated with promising efficacy against pretreated advanced nonsquamous NSCLC.