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The changes of lipid metabolism in advanced renal cell carcinoma patients treated with everolimus: a new pharmacodynamic marker?

Pantano F, Santoni M, Procopio G, Rizzo M, Iacovelli R, Porta C, Conti A, Lugini A, Milella M, Galli L, Ortega C, Guida FM, Silletta M, Schinzari G, Verzoni E, Modica D, Crucitti P, Rauco A, Felici A, Ballatore V, Cascinu S, Tonini G, Carteni G, Russo A, Santini D - PLoS ONE (2015)

Bottom Line: Basal BMI was significantly higher in patients who experienced a CB (p=0,0145).C,T and C+T raises were significantly associated with baseline BMI (p=0.0412, 0.0283 and 0.0001).At the multivariate analysis, only C+T increase was associated with improved TTP (p=0.005).

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Oncology, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128 Rome, Italy.

ABSTRACT

Background: Everolimus is a mammalian target of rapamycin (mTOR) inhibitor approved for the treatment of metastatic renal cell carcinoma (mRCC). We aimed to assess the association between the baseline values and treatmentrelated modifications of total serum cholesterol (C), triglycerides (T), body mass index (BMI), fasting blood glucose level (FBG) and blood pressure (BP) levels and the outcome of patients treated with everolimus for mRCC.

Methods: 177 patients were included in this retrospective analysis. Time to progression (TTP), clinical benefit (CB) and overall survival (OS) were evaluated.

Results: Basal BMI was significantly higher in patients who experienced a CB (p=0,0145). C,T and C+T raises were significantly associated with baseline BMI (p=0.0412, 0.0283 and 0.0001). Median TTP was significantly longer in patients with T raise compared to patients without T (10 vs 6, p=0.030), C (8 vs 5, p=0.042) and C+T raise (10.9 vs 5.0, p=0.003). At the multivariate analysis, only C+T increase was associated with improved TTP (p=0.005). T raise (21.0 vs 14.0, p=0.002) and C+T increase (21.0 vs 14.0, p=0.006) were correlated with improved OS but were not significant at multivariate analysis.

Conclusion: C+T raise is an early predictor for everolimus efficacy for patients with mRCC.

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Related in: MedlinePlus

Correlation between change in C (panel A), T (panel B), C+T (panel C) and basal BMI (panel D) with OS during everolimus therapy.
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pone.0120427.g003: Correlation between change in C (panel A), T (panel B), C+T (panel C) and basal BMI (panel D) with OS during everolimus therapy.

Mentions: In order to assess the impact of basal biomarkers on clinical outcome we divided the study population into two groups for each parameter according the presence of elevated FBG (cut-off 100 mg/dl sec. International Diabetes Federation (IDF) criteria of metabolic syndrome [22]; median basal value: 95 mg/dl; range: 65–243 mg/dl), BP (cut-off 130 mm/Hg for systolic pressure and 85 mm/Hg for diastolic pressure sec. IDF criteria;22 median basal value: 130 mm/Hg; range 100–160 mm/Hg for systolic BP and 80; range 60–140 mm/Hg for diastolic BP), C (cut-off 200 mg/dL sec. AACE Criteria [23]; median basal value: 187 mg/dl, range: 115–407 mg/dl), T (150 mg/dl sec. IDF criteria [22]; median basal value: 151 mg/dl; range: 56–560 mg/dl) and BMI (cutoff 24.99 sec. WHO Criteria [24]; median BMI: 25.60; range: 17.72–37.11). None of these basal biomarkers correlated with an improved TTP or OS (Table 3). Basal BMI was significantly higher in patients who experienced a CB compared to those with PD as best response during treatment with everolimus 25.91 (95% C.I. 25.34–26.73) vs 23.22 (95% C.I.: 23.11–25.61) (p = 0,0145—Fig 1, panel D). Finally, TTP (15.71 vs 9.23 months, p = 0.013—Fig 2, panel D) and OS (23.02 vs 16.11 months, p = 0.027—Fig 3, panel D) were significantly higher in the 87 patients with elevated basal BMI compared to the 90 patients with normal or low BMI, even if in multivariate analysis this parameter did not demonstrate to be as an independent predictive factor (Table 3).


The changes of lipid metabolism in advanced renal cell carcinoma patients treated with everolimus: a new pharmacodynamic marker?

Pantano F, Santoni M, Procopio G, Rizzo M, Iacovelli R, Porta C, Conti A, Lugini A, Milella M, Galli L, Ortega C, Guida FM, Silletta M, Schinzari G, Verzoni E, Modica D, Crucitti P, Rauco A, Felici A, Ballatore V, Cascinu S, Tonini G, Carteni G, Russo A, Santini D - PLoS ONE (2015)

Correlation between change in C (panel A), T (panel B), C+T (panel C) and basal BMI (panel D) with OS during everolimus therapy.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4401714&req=5

pone.0120427.g003: Correlation between change in C (panel A), T (panel B), C+T (panel C) and basal BMI (panel D) with OS during everolimus therapy.
Mentions: In order to assess the impact of basal biomarkers on clinical outcome we divided the study population into two groups for each parameter according the presence of elevated FBG (cut-off 100 mg/dl sec. International Diabetes Federation (IDF) criteria of metabolic syndrome [22]; median basal value: 95 mg/dl; range: 65–243 mg/dl), BP (cut-off 130 mm/Hg for systolic pressure and 85 mm/Hg for diastolic pressure sec. IDF criteria;22 median basal value: 130 mm/Hg; range 100–160 mm/Hg for systolic BP and 80; range 60–140 mm/Hg for diastolic BP), C (cut-off 200 mg/dL sec. AACE Criteria [23]; median basal value: 187 mg/dl, range: 115–407 mg/dl), T (150 mg/dl sec. IDF criteria [22]; median basal value: 151 mg/dl; range: 56–560 mg/dl) and BMI (cutoff 24.99 sec. WHO Criteria [24]; median BMI: 25.60; range: 17.72–37.11). None of these basal biomarkers correlated with an improved TTP or OS (Table 3). Basal BMI was significantly higher in patients who experienced a CB compared to those with PD as best response during treatment with everolimus 25.91 (95% C.I. 25.34–26.73) vs 23.22 (95% C.I.: 23.11–25.61) (p = 0,0145—Fig 1, panel D). Finally, TTP (15.71 vs 9.23 months, p = 0.013—Fig 2, panel D) and OS (23.02 vs 16.11 months, p = 0.027—Fig 3, panel D) were significantly higher in the 87 patients with elevated basal BMI compared to the 90 patients with normal or low BMI, even if in multivariate analysis this parameter did not demonstrate to be as an independent predictive factor (Table 3).

Bottom Line: Basal BMI was significantly higher in patients who experienced a CB (p=0,0145).C,T and C+T raises were significantly associated with baseline BMI (p=0.0412, 0.0283 and 0.0001).At the multivariate analysis, only C+T increase was associated with improved TTP (p=0.005).

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Oncology, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128 Rome, Italy.

ABSTRACT

Background: Everolimus is a mammalian target of rapamycin (mTOR) inhibitor approved for the treatment of metastatic renal cell carcinoma (mRCC). We aimed to assess the association between the baseline values and treatmentrelated modifications of total serum cholesterol (C), triglycerides (T), body mass index (BMI), fasting blood glucose level (FBG) and blood pressure (BP) levels and the outcome of patients treated with everolimus for mRCC.

Methods: 177 patients were included in this retrospective analysis. Time to progression (TTP), clinical benefit (CB) and overall survival (OS) were evaluated.

Results: Basal BMI was significantly higher in patients who experienced a CB (p=0,0145). C,T and C+T raises were significantly associated with baseline BMI (p=0.0412, 0.0283 and 0.0001). Median TTP was significantly longer in patients with T raise compared to patients without T (10 vs 6, p=0.030), C (8 vs 5, p=0.042) and C+T raise (10.9 vs 5.0, p=0.003). At the multivariate analysis, only C+T increase was associated with improved TTP (p=0.005). T raise (21.0 vs 14.0, p=0.002) and C+T increase (21.0 vs 14.0, p=0.006) were correlated with improved OS but were not significant at multivariate analysis.

Conclusion: C+T raise is an early predictor for everolimus efficacy for patients with mRCC.

Show MeSH
Related in: MedlinePlus