Dataset Information

A phase I/II study of pemetrexed with sirolimus in advanced, previously treated non-small cell lung cancer.

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).

SUBMITTER: Komiya T

PROVIDER: S-EPMC6626857 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Publications

A phase I/II study of pemetrexed with sirolimus in advanced, previously treated non-small cell lung cancer.

Komiya Takefumi T Memmott Regan M RM Blumenthal Gideon M GM Bernstein Wendy W Ballas Marc S MS De Chowdhury Roopa R Chun Guinevere G Peer Cody J CJ Figg William D WD Liewehr David J DJ Steinberg Seth M SM Giaccone Giuseppe G Szabo Eva E Kawabata Shigeru S Tsurutani Junji J Rajan Arun A Dennis Phillip A PA

Translational lung cancer research 20190601 3

<h4>Background</h4>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.<h4>Methods</h4>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 saf ...[more]

PMID: 31367538

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Dataset Information

A phase I/II study of pemetrexed with sirolimus in advanced, previously treated non-small cell lung cancer.

Background

Methods

Results

Conclusions

Publications

A phase I/II study of pemetrexed with sirolimus in advanced, previously treated non-small cell lung cancer.

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