Although the clinical efficacy of radiation therapy (RT) has been demonstrated in elderly patients with locally advanced non-small-cell lung cancer (NSCLC), the combination of pemetrexed (PEM) and RT has not been examined in clinical trials yet. Therefore, we conducted a phase I / II study to evaluate the appropriate PEM dose, efficacy and safety of PEM plus RT in elderly patients with locally advanced NSCLC.
Eligibility criteria included performance status (PS) 0-2, aged 71 years or older, pathologically confirmed NSCLC, locally advanced stage (IIIA / IIIB), adequate organ function, and written informed consent. Patients received PEM (500mg/m2 on day1 of a 28-day cycle, 4 course) and RT (total 60 Gy / 30 fractions over 6 weeks). The primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and adverse events (AEs).
A total of 41 patients (4 patients in phase I, 37 patients in phase II) were enrolled. Median age was 79 years old (range 71-87) and 31 patients were male. Eighteen patients were squamous cell carcinoma, 27 of 41 patients were stage IIIA, and 38 patients were PS 0-1. ORR was 80.5%. Median OS was 24.6 months and median PFS was 6.8 months. There were 2 treatment related deaths, caused by RT pneumonitis in one patient and severe infection in one patient. Common hematological AEs were leucopenia and neutropenia, whereas, common non-hematological AEs were anorexia and constipation. Interstitial lung disease caused by PEM developed in 3 patients. RT related AEs were mainly observed, including radiation esophagitis (grade 1: 22 patients, 2: 6 patients, 3: 1 patient) and RT pneumonitis (grade 1: 11 patients, 2: 14 patients, 3: 7 patients, 5: 1 patient).
This combination treatment shows promising activity, but RT related toxicities were relatively severe. Therefore, the use of this treatment require close caution for elderly patients.
Clinical trial identification
Legal entity responsible for the study
National hospital organization network funding
S. Atagi: Honoraria: Eli Lilly Japan, Chugai, Taiho, Boehringer Ingelheim, Pfizer Japan, Ono, and AstraZeneca. Research Funding: Chugai, Pfizer, Ono, Merck Serono, Boehringer Ingelheim, AstraZeneca, Taiho, Yakult, Eli Lilly. N. Nogami: Honoraria: Chugai, Taihou, Eli Lilly, Pfizer, AstraZeneca, Ono, BMS, Nippon Boehringer. All other authors have declared no conflicts of interest.