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Metformin's role in response to induction chemotherapy for multimodal treated head and neck cancers in diabetic patients

Mireștean Camil Ciprian, Paguțe Ovidiu Nicolae, Cîrdei Simona, Apostu Raluca, Buzea Călin, Teacă Cătălina, Roman Ramona, Iancu Roxana Irina, Iancu Dragoș Teodor

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy and recent sequencing of the HNSCC genomic demonstrate the potential of targeting the m-TOR pathway in the treatment of these malignancies. Metformin is one of the most widely prescribed oral anti-diabetic drug but some preclinical evidence suggesting that metformin has anti-cancer properties leading to the inhibition of m-TOR pathway.Metformin plays also a role in modulation of the immune system by potentiating the action of T lymphocyte on the tumor cell and reduces the Warburg effect characteristic of the tumor cell where tumor cells generate ATP from glycolysis in conditions of poor nutrition and hypoxia. The association of Metformin with platinum-based chemotherapy and radiotherapy has shown in some studies potentially synergistic and radio-sensitization.
Some trials demonstrate the benefit of sequential chemotherapy, (induction chemotherapy followed by radiotherapy or concurrent chemo-radiotherapy). The purpose of the study is to evaluate comparatively the imaging response (RECIST CRITERIA) to induction chemotherapy in patients diagnosed with diabetes and head and neck cancers treated with Metformin or not with the induction chemotherapy response of patients without metabolic comorbidities. The results can comparatively evaluate the platinum sensitivity for diabetic patients and the influence of Metformin in the modulation of this sensitivity.The study also aims to compare the benefit of induction chemotherapy to patients who associate diabetes mellitus with advanced local head and neck cancers proposed for multidisciplinary treatment.

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