A Phase II Randomized Trial of Chemoradiation with or without Metformin in Locally Advanced Cervical Cancer.
Clin Cancer Res
; 28(24): 5263-5271, 2022 12 15.
Article
em En
| MEDLINE
| ID: mdl-36037303
ABSTRACT
PURPOSE:
Tumor hypoxia is associated with poor response to radiation (RT). We previously discovered a novel mechanism of metformin enhancing tumor RT response by decreasing tumor hypoxia. We hypothesized that metformin would decrease tumor hypoxia and improve cervical cancer response to RT. PATIENTS ANDMETHODS:
A window-of-opportunity, phase II randomized trial was performed in stage IB-IVA cervical cancer. Patients underwent screening positron emission tomography (PET) imaging with hypoxia tracer fluoroazomycin arabinoside (FAZA). Only patients with FAZA uptake (hypoxic tumor) were included and randomized 21 to receive metformin in combination with chemoRT or chemoRT alone. A second FAZA-PET/CT scan was performed after 1 week of metformin or no intervention (control). The primary endpoint was a change in fractional hypoxic volume (FHV) between FAZA-PET scans, compared using the Wilcoxon signed-rank test. The study was closed early due to FAZA availability and the COVID-19 pandemic.RESULTS:
Of the 20 consented patients, 6 were excluded due to no FAZA uptake and 1 withdrew. FHV of 10 patients in the metformin arm decreased by an average of 10.2% (44.4%-34.2%) ± SD 16.9% after 1 week of metformin, compared with an average increase of 4.7% (29.1%-33.8%) ± 11.5% for the 3 controls (P = 0.027). Those with FHV reduction after metformin had significantly lower MATE2 expression. With a median follow-up of 2.8 years, the 2-year disease-free survival was 67% for the metformin arm versus 33% for controls (P = 0.09).CONCLUSIONS:
Metformin decreased cervical tumor hypoxia in this trial that selected for patients with hypoxic tumor. See related commentary by Lyng et al., p. 5233.
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
4_TD
Base de dados:
MEDLINE
Assunto principal:
Neoplasias do Colo do Útero
/
COVID-19
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Metformina
/
Nitroimidazóis
Tipo de estudo:
Clinical_trials
Limite:
Female
/
Humans
Idioma:
En
Revista:
Clin Cancer Res
Ano de publicação:
2022
Tipo de documento:
Article