A phase I/II study of pemetrexed with sirolimus in advanced, previously treated non-small cell lung cancer.
Lung cancer
pemetrexed
phase I/II, sirolimus
thymidylate synthase (TS)
Journal
Translational lung cancer research
ISSN: 2218-6751
Titre abrégé: Transl Lung Cancer Res
Pays: China
ID NLM: 101646875
Informations de publication
Date de publication:
Jun 2019
Jun 2019
Historique:
entrez:
2
8
2019
pubmed:
2
8
2019
medline:
2
8
2019
Statut:
ppublish
Résumé
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. 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. Forty-two patients with recurrent, metastatic NSCLC were enrolled, 22 in phase I and 20 in phase II. The MTD was pemetrexed 500 mg/m The combination of pemetrexed and sirolimus is active in heavily-pretreated NSCLC (ClinicalTrials.gov Identifier: NCT00923273).
Sections du résumé
BACKGROUND
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
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
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/m
CONCLUSIONS
CONCLUSIONS
The combination of pemetrexed and sirolimus is active in heavily-pretreated NSCLC (ClinicalTrials.gov Identifier: NCT00923273).
Identifiants
pubmed: 31367538
doi: 10.21037/tlcr.2019.04.19
pii: tlcr-08-03-247
pmc: PMC6626857
doi:
Banques de données
ClinicalTrials.gov
['NCT00923273']
Types de publication
Journal Article
Langues
eng
Pagination
247-257Déclaration de conflit d'intérêts
Conflicts of Interest: Phillip A. Dennis is employed by Astrazeneca and owns its stocks. Marc S. Ballas is employed by GlaxoSmithKline and receives personal fees from Astrazeneca and Bristol Myers Squibb. The other authors have no conflicts of interest to declare.
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