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- W2891117532 abstract "e14020 Background: Fundamental research suggests that a combination of everolimus and metformin has synergistic anti-tumour effects with lower chances of drug resistance. Methods: 9 patients with advanced refractory cancer received everolimus and metformin in a 3+3 dose-escalation scheme. Objectives were to determine the dose-limiting toxicities (DLTs), maximum tolerated dose, toxic effects, pharmacokinetics and anti-tumour efficacy. Results: We enrolled 9 patients who stayed on the study for a median duration of 48 days (range: 4-78). 6 patients discontinued due to toxicity and 3 patients because of progressive disease. 4 out of 9 patients experienced a DLT and we terminated patient enrollment. Metformin was eliminated slower and metformin trough concentrations were higher when co-administered with everolimus than as single-agent (half-life: 9.3 h vs 4.3 h; P= .03 and C trough : 0.47 mg/l vs 0.2 mg/l; P =.01). After 9 weeks of treatment, 3 patients were still on study and all had stable disease as evaluated using CT scans and RECIST criteria. The 3 patients that received everolimus and metformin for at least 9 weeks had a significantly longer survival than the 5 patients who had to stop study treatment prematurely due to toxicity (median overall survival: 184 days vs 82 days; P= .048). Conclusions: The combination of everolimus and metformin is poorly tolerated in patients with advanced cancer. This may be due to pharmacokinetic interactions between everolimus and metformin and has implications for diabetic cancer patients that are treated with these drugs. Patients that tolerated the combination survived longer than patients who did not, suggesting that the combination of an mTOR inhibitor and metformin is clinically effective against cancer. This advocates for future clinical trials with combinations of other mTOR inhibitors and biguanides. [Table: see text]" @default.
- W2891117532 created "2018-09-27" @default.
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- W2891117532 date "2017-05-20" @default.
- W2891117532 modified "2023-09-27" @default.
- W2891117532 title "Survival analysis of a phase IB/II study of everolimus and metformin for patients with advanced cancer." @default.
- W2891117532 doi "https://doi.org/10.1200/jco.2017.35.15_suppl.e14020" @default.
- W2891117532 hasPublicationYear "2017" @default.
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