Phase I Study of Pemetrexed and Concurrent Radiotherapy for Previously Untreated Elderly Patients with Locally Advanced Non-squamous Non-small Cell Lung Cancer

Background: Chemoradiotherapy is the standard treatment for locally advanced non-small cell lung cancer (NSCLC); however, it is disputed whether this treatment is suitable for patients aged ≥75. This study was conducted to determine the maximum tolerated dose (MTD) of pemetrexed for use in concurrent radiotherapy for elderly patients with locally advanced non-squamous NSCLC.

Methods: The eligibility criteria were as follows: aged ≥75 with inoperable stage IIIA or IIIB non-squamous NSCLC, no history of chemotherapy or radiotherapy, a performance status of 0 or 1, and adequate organ function. The patients were scheduled to receive pemetrexed on days 1, 22, 43, and 64 with concurrent once daily thoracic radiotherapy (60 Gy). The initial pemetrexed dose was 400 (level 1), and it was planned to increase the dose to 500 mg/m (level 2).

Results: Two patients were enrolled in this trial. In the first case, the patient suffered prolonged leukocytopenia, and treatment was discontinued on day 35. In the second case, febrile neutropenia occurred on day 32, and the patient developed drug-induced pneumonitis and acute respiratory distress syndrome. Both patients experienced dose-limiting toxicities; therefore, the level 1 dose was considered to be the MTD.

Conclusions: During combined treatment with pemetrexed and concurrent radiotherapy, a pemetrexed dose of 400 mg/m was the MTD; we did not set up a phase II study. Concurrent chemoradiotherapy might be too toxic for elderly patients aged ≥75 with locally advanced NSCLC.