Randomized phase II study of platinum-based chemotherapy plus controlled diet with or without metformin in patients with advanced non-small cell lung cancer
Mené sur 164 patients atteints d'un cancer du poumon non à petites cellules de stade avancé, cet essai de phase II évalue l'efficacité, du point de vue de la progression de la maladie, de la survie, et de la réduction du risque de décès, de l'ajout de la metformine à une chimiothérapie à base de sels de platine
Objectives : Accumulating evidence indicates anti-diabetic drug metformin has anti-cancer effectby controlling cancer metabolism. We evaluated whether addition of metformin to chemotherapy improved survival of lung cancer patients. Materials and methods : This randomized phase II study enrolled 164 patients with chemo-native, EGFR-ALK wild-type, stage IIIB/IV non-small-cell lung cancer (NSCLC). Patients were randomized to receive chemotherapy either with metformin (1000 mg twice daily) or alone every3 weeks for six cycles. The patients received gemcitabine (1000 mg/m 2) on days 1 and 8 and 5 area under the curve carboplatin on day 1. Exploratory studies included serum metabolic panels, positron-emission tomography (PET) imaging, and genetic mutation tests for metabolism-related genes. Results : Metformin group showed no significant difference in the risk of progression or death compared to the control group (progression: hazard ratio [HR] = 1.01 [95% confidenceinterval (CI) = 0.72 − 1.42], P = 0.935; death: HR = 0.95 [95% CI = 0.67–1.34], P = 0.757). Squamous cell carcinoma (SqCC) had significantly higher fluorodeoxyglucose(FDG) uptake on baseline PET image than non-SqCC NSCLC ( P = 0.004). In the SqCC with high FDG uptake, the addition of metformin significantly decreased the risk of progression and death (progression: HR = 0.31 [95% CI = 0.12−0.78], P = 0.013; death: HR = 0.42 [95% CI = 0.18–0.94], P = 0.035). The HDL-cholesterol level was significantly increased after the treatmentin metformin group compared to control group ( P = 0.011). The metformin group showed no survival benefit in the patients with hyperinsulinemia or patients whose insulin level was decreased after treatment. Conclusions : Addition of metformin to chemotherapy provided no survival benefit in unselected NSCLC patients. However, it significantly improved the survival of the selected patients with SqCC showing high FDG uptake. It suggests metformin shows the synergistic anti-tumor effect in the tumor which are highly dependent on glucose metabolism.
Lung Cancer 2020