Phase I study of pemetrexed and concurrent radiotherapy for previously untreated elderly patients with locally advanced non‐squamous non‐small cell lung cancer

Abstract

BackgroundChemoradiotherapy 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.MethodsThe 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/m2 (level 2).ResultsTwo 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.ConclusionsDuring combined treatment with pemetrexed and concurrent radiotherapy, a pemetrexed dose of 400 mg/m2 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.

Phase I dose escalation study of pemetrexed and concurrent thoracic radiation in elderly patients with non-squamous non–small-cell lung cancer

“…However, the response rate of 66.7% is comparable with that of other studies, and the median overall survival was >5 years. Recently, Takemoto et al reported the results of a Phase I dose escalation study similar to ours in elderly patients with LA-NSCLC [12]. In their study, two patients were enrolled at pemetrexed Dose Level 1 (400 mg/m 2 ); however, one patient, who experienced prolonged leukopenia and chemoradiotherapy, was discontinued on Day 35.…”

Real-World Incidence of Febrile Neutropenia among Patients Treated with Single-Agent Amrubicin: Necessity of the Primary Prophylactic Administration of Granulocyte Colony-Stimulating Factor

“…It is interesting to note that single-agent amrubicin treatment in elderly patients was not a risk factor in the present study, whether they were 65 years or older or 75 years or older. Although chemotherapy in elderly patients is known to have different results than in younger patients [ 32 , 33 , 34 ], it is presumed that chemotherapy can safely be administered to even elderly patients with good PS and an appropriate dose setting. An amrubicin dose of 45 mg/m 2 was a factor for longer OS, and decrease in dose before treatment was a risk factor.…”

Dabrafenib and trametinib therapy in an elderly patient with non‐small cell lung cancer harboring the BRAF V600E mutation

“…There is limited clinical information about patients harboring BRAF mutations, especially in elderly patients and those with poor PS, because BRAF mutations are only found in a few populations. Intensive treatment, such as combination chemotherapy or combined modality, does not usually produce a survival benefit in patients aged >70 or 75 years 12–14 . On the other hand, the use of therapies targeting other driver oncogenes is recommended, regardless of the patient's age and general condition, because of the marked responses they induce and their mild toxicities 15–17 .…”

“…Intensive treatment, such as combination chemotherapy or combined modality, does not usually produce a survival benefit in patients aged >70 or 75 years. [12][13][14] On the other hand, the use of therapies targeting other driver oncogenes is recommended, regardless of the patient's age and general condition, because of the marked responses they induce and their mild toxicities. [15][16][17] However, the patient in the present case was 86 years old, which is classified as "oldest old", and the supportive care rates in this age group range from 55%-67%.…”