A phase I dose-escalating study of combination pemetrexed-based chemotherapy and concomitant radiotherapy for locally advanced or metastatic non-small cell lung or esophageal cancer

Abstract

7062 Background: Pemetrexed (pem, Alimta) is a multitargeted antifolate approved for second-line treatment of metastatic non-small cell lung cancer (NSCLC). Treatment failure with chemoradiotherapy (CRT) is frequently due to development of distant metastasis suggesting a potential need for more effective systemic therapy. The primary objective was to determine whether pem based CRT allows administration of systemically active chemotherapy doses. Methods: Patients (pts) with locally advanced or metastatic (dominant local symptoms) NSCLC or esophageal cancer (ca) were enrolled in a phase I dose-escalating study with chemotherapy delivered on day 1, every 21 days for 2 cycles. Schedule 1 was pem (200–600 mg/m2) with concurrent radiotherapy (RT) 40–66Gy (2 Gy/d). Schedule 2 was pem fixed at recommended single-agent dose (500 mg/m2) and escalating carboplatin doses (AUC 4–6) + concomitant RT (40–66Gy). Results: 30 pts (18 locally advanced, 12 metastatic disease) were enrolled. ECOG performance status was 0 (8 pts, 26.7%), 1 (21 pts, 70.0%), and 2 (1 pt, 3.3%). Schedule 1 enrolled 18 pts (15 NSCLC, 3 esophageal ca); all dose levels were tolerable. One DLT (Grade [Gr] 4 esophagitis) was reported. One pt developed Gr 4 pulmonary embolism (PE) at the end of therapy. Gr 3 toxicities were leukopenia (n=3), dysphagia (1), and dehydration (1). Schedule 2 enrolled 12 NSCLC pts; all dose levels were tolerated. One DLT (Gr 4 PE) was reported at 500 mg/m2 + AUC 6. One pt had Gr 4 leukopenia at 500 mg/m2 + AUC 5. Treatment-related grade 3 toxicities were leukopenia (n=3), dehydration (1), and fatigue (1). Overall responses for Schedule 1 were PR (n=5), SD (5), PD (6), and unknown (2); for Schedule 2, pts had CR (1), PR (3), SD (4), PD (1), and unknown (3). Study is on-going. 3 pts had Gr 1/2 radiation pneumonitis (8 d - 8 w) after RT. Several pts underwent curative intent surgery. In-field responses are being assessed. Conclusions: The combination of pemetrexed (500 mg/m2) with carboplatin (AUC 6) day 1 every 21 days for 2 cycles with concurrent radiotherapy is feasible, allows administration of systemically active doses, and warrants examination in a phase II trial. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly Eli Lilly Eli Lilly Eli Lilly