@article{TLCR28755,
author = {Takefumi Komiya and Regan M. Memmott and Gideon M. Blumenthal and Wendy Bernstein and Marc S. Ballas and Roopa De Chowdhury and Guinevere Chun and Cody J. Peer and William D. Figg and David J. Liewehr and Seth M. Steinberg and Giuseppe Giaccone and Eva Szabo and Shigeru Kawabata and Junji Tsurutani and Arun Rajan and Phillip A. Dennis},
title = {A phase I/II study of pemetrexed with sirolimus in advanced, previously treated non-small cell lung cancer},
journal = {Translational Lung Cancer Research},
volume = {8},
number = {3},
year = {2019},
keywords = {},
abstract = {Background: Single-agent pemetrexed is a treatment for recurrent non-squamous non-small cell lung cancer (NSCLC) that provides limited benefit. Preclinical studies showed promising synergistic effects when the mammalian target of rapamycin (mTOR) inhibitor sirolimus was added to pemetrexed.
Methods: This was a single-institution phase I/II study of pemetrexed in combination with sirolimus. The primary endpoint for the phase I was to determine the maximum tolerated dose (MTD) and safety of the combination. The primary endpoint for the phase II portion was to determine the overall response rate at the MTD. Key eligibility criteria included recurrent, metastatic NSCLC, ECOG performance status of 0–2, and adequate organ function. Sirolimus was administered orally daily after an initial loading dose, and pemetrexed was given intravenously on day 1 of every 21-day cycle.
Results: Forty-two patients with recurrent, metastatic NSCLC were enrolled, 22 in phase I and 20 in phase II. The MTD was pemetrexed 500 mg/m2 every 3 weeks, and sirolimus 10 mg on day 1, and 3 mg daily thereafter. Treatment-related adverse events (AEs) occurred in 38 (90.5%) patients. The most common grade 3–4 treatment-related AEs were lymphopenia (31%) and hypophosphatemia (19%). Two treatment-related deaths occurred due to febrile neutropenia and infection, respectively. Among 27 total patients treated at the MTD, 6 (22.2%) had a partial response (PR), 12 (44.4%) had stable disease (SD) and 5 (18.5%) had progressive disease. Median progression-free survival (PFS) was 18.4 weeks (95% CI: 7.0–29.4).
Conclusions: The combination of pemetrexed and sirolimus is active in heavily-pretreated NSCLC (ClinicalTrials.gov Identifier: NCT00923273).},
issn = {2226-4477}, url = {https://tlcr.amegroups.org/article/view/28755}
}