Biological toxicities as surrogate markers of efficacy in patients treated with mTOR inhibitors for metastatic renal cell carcinoma. Issue 1 (December 2017)

• Record Type: Journal Article
• Authors: Jebali, M.; Elaidi, R.; Brizard, M.; Fouque, J.; Takouchop, C.; Sabatier, B.; Oudard, S.; Medioni, J.
• Is Part Of: BMC cancer. Volume 17:Issue 1(2017)
• Page Start: 1
• Page End: 7
• Publication Date: 2017-12
• Subjects: Drug-related side effects -- Adverse reactions -- mTOR inhibitors -- Metastatic renal cell carcinoma -- Biomarkers; Cancer -- Periodicals; 616.994005
• DOI: 10.1186/s12885-016-2993-7
• Languages: English
• ISSNs: 1471-2407

Abstract

Abstract Background Metabolic toxicities of mTOR inhibitors (mTORi) are well characterized. The purpose of the study was to investigate the relationship between these metabolic toxicities and mTORi efficacy. Methods From 2007 to 2011, metabolic toxicities were retrospectively collected in patients treated with an mTORi (everolimus, temsirolimus) for a metastatic renal cell carcinoma (mRCC) in a single institution. Patients were eligible if they have received an mTORi for at least 28 days. Changes in the following parameters were analyzed: lymphocytes, serum creatinine, glycemia, serum phosphate, liver transaminases, cholesterol, and triglycerides. The efficacy was assessed by progression-free survival (PFS) and tumor response. Results Data were collected from seventy-five patients (everolimus = 44 patients; temsirolimus = 31 patients). Six patients exhibited a partial response, 42 a stable disease and 15 had a progressive disease (12 missing). After a median follow-up of 12.8 months, the median PFS was 6.7 months (95% confidence interval: 4.0-9.1 months). Patients with CB had a statistically more severe absolute increase of glycemia and absolute decrease in phosphatemia (p = 0.002 andp = 0.02 respectively). The Progression Free Survival was significantly higher with the onset rate of hypophosphatemia (p = 0.03) and hyperglycemia (p = 0.001) and lower with the onset rate of lymphopenia (p = 0.004). Conclusions Hyperglycemia, hypophosphatemia and lymphopenia, were significantly associated with tumor response and/or PFS. Those events, as well as their onset rate, should be prospectively monitored as predictors of response to mTORi.