A phase I/II trial of pemetrexed plus radiotherapy in elderly patients with locally advanced non-small cell lung cancer

Abstract

Background Radiotherapy (RT) is an effective treatment for elderly patients with locally advanced non-small-cell lung cancer (NSCLC); however, no clinical trials have investigated combination RT with pemetrexed (PEM) in chemotherapy-naive patients ≥71 years old. We conducted a phase I/II study to evaluate the appropriate PEM dose, efficacy, and safety of PEM plus RT in elderly patients. Methods Patients ≥71 years with performance status (PS) scores of 0-2 who had pathologically confirmed stage IIIA/IIIB NSCLC received PEM (500 mg/m on day 1 of a 28-day cycle, 4 courses) and RT (a single 2 Gy daily fraction on 5 consecutive days weekly from day 1; 60 Gy total). The primary endpoint was the objective response rate (ORR); the secondary endpoints were progression-free survival (PFS), overall survival (OS), and adverse events (AEs). Results Forty-one patients with a median age of 79 years were enrolled; 31 were men. Eighteen patients had squamous cell carcinoma, 27 had stage IIIA disease, and 38 had PS scores 0-1. The ORR was 80.5%, while the median OS and PFS rates were 24.9 and 6.9 months, respectively. Two treatment-related deaths occurred owing to RT-related pneumonitis and severe infection, respectively. Common hematological AEs were leucopenia and neutropenia; common non-hematological AEs were anorexia and constipation. Three patients developed PEM-induced interstitial lung disease; however, most AEs were RT-related. Conclusions Combination PEM and RT shows promising efficacy but relatively severe RT-related toxicities. Therefore, this treatment should be prescribed to elderly patients with caution. Trial registration UMIN 000005036 .

Phase I Study of Weekly Nab-Paclitaxel Plus Carboplatin And Concurrent Thoracic Radiotherapy in Elderly Patients with Unresectable Locally Advanced Non-Small-Cell Lung Cancer

“…Treatment completion was de ned as the receipt of at least ve doses of nab-paclitaxel plus carboplatin and 64 Gy of thoracic radiotherapy within 58 days from the start of treatment. We considered tolerability and safety to be the most important aspects for elderly Japanese patients because severe lung toxicities have been reported in these patients [11,12]. In addition, we considered that the regimen to be effective if the tolerability was the same as that of carboplatin/paclitaxel in non-elderly patients with locally advanced NSCLC [5].…”

“…However, due to the high incidence of pulmonary toxicities or non-platinum chemotherapy regimen not adapted to durvalumab, neither of these treatments was further developed. In a study using chemoradiotherapy with pemetrexed, although the objective response of the primary endpoint was met with 80.5%, grade 3 or higher pneumonitis was observed in 8 out of 41 patients (19.5%) [12]. Therefore, it was concluded that chemoradiotherapy with pemetrexed should be prescribed to elderly patients with caution.…”