Biological toxicities as surrogate markers of efficacy in patients treated with mTOR inhibitors for metastatic renal cell carcinoma

BMC Cancer

Research Article

R. Elaidi¹  C. Takouchop¹  M. Jebali²  M. Brizard³  S. Oudard⁴  J. Medioni⁴  J. Fouque⁵  B. Sabatier⁵ 

[1] Association pour la Recherche sur les Thérapeutiques Innovantes en Cancérologie (ARTIC), Hôpital Européen Georges Pompidou, Paris, France;Department of Medical Oncology (Centre d’Essais Clinique Précoces en Cancérologie [CEPEC]), Hôpital Européen Georges Pompidou, 20 rue Leblanc, 75015, Paris, France;Department of Medical Oncology (Centre d’Essais Clinique Précoces en Cancérologie [CEPEC]), Hôpital Européen Georges Pompidou, 20 rue Leblanc, 75015, Paris, France;Association pour la Recherche sur les Thérapeutiques Innovantes en Cancérologie (ARTIC), Hôpital Européen Georges Pompidou, Paris, France;Department of Medical Oncology (Centre d’Essais Clinique Précoces en Cancérologie [CEPEC]), Hôpital Européen Georges Pompidou, 20 rue Leblanc, 75015, Paris, France;Paris Descartes University, Paris, France;Department of Pharmacy, Hôpital Européen Georges Pompidou, Paris, France;

关键词: Drug-related side effects;    Adverse reactions;    mTOR inhibitors;    Metastatic renal cell carcinoma;    Biomarkers;   

DOI  :  10.1186/s12885-016-2993-7

 received in 2016-05-03, accepted in 2016-12-13,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundMetabolic 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.MethodsFrom 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.ResultsData 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 and p = 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).ConclusionsHyperglycemia, 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.

【 授权许可】

CC BY   
© The Author(s). 2017