Abstract | PURPOSE: EXPERIMENTAL DESIGN: We examined serial measurements of cholesterol, triglycerides, and glucose from patients randomized to IFN or temsirolimus in the Global Advanced Renal Cell Carcinoma Trial. Using time-dependent proportional hazards models, we quantified the association between changes in these biomarkers from baseline with overall survival (OS) and progression-free survival (PFS). We also assess the extent to which changes of these biomarkers predict the effects of temsirolimus on survival. RESULTS:
Temsirolimus was associated with larger mean increases in cholesterol (1.02 mmol/L; P < 0.0001), triglycerides (0.32 mmol/L; P = 0.0008), and glucose (1.28 mmol/L; P < 0.0001) compared with IFN and improved survival rate (OS: HR = 0.76, P = 0.02; PFS: HR = 0.70, P = 0.001). Cholesterol increase during study was associated with longer survival (OS: HR = 0.77 per mmol/L, P < 0.0001; PFS: HR = 0.81 per mmol/L; P < 0.0001). Temsirolimus effect on cholesterol predicted its effect on survival with no additional survival advantage observed after adjusting for cholesterol change during study (OS: HR = 1.14, P = 0.37; PFS: HR = 0.88, P = 0.35). Temsirolimus effect on triglycerides or glucose did not predict its effect on survival, with survival advantage in favor of temsirolimus still observed after adjusting for these factors (P = 0.003 and P = 0.002). CONCLUSION:
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Authors | Chee Khoon Lee, Ian C Marschner, R John Simes, Merryn Voysey, Brian Egleston, Gary Hudes, Paul de Souza |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 18
Issue 11
Pg. 3188-96
(Jun 01 2012)
ISSN: 1557-3265 [Electronic] United States |
PMID | 22472176
(Publication Type: Journal Article)
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Chemical References |
- Antineoplastic Agents
- Biomarkers, Tumor
- Blood Glucose
- Triglycerides
- temsirolimus
- Cholesterol
- Sirolimus
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Topics |
- Adult
- Aged
- Aged, 80 and over
- Antineoplastic Agents
(therapeutic use)
- Biomarkers, Tumor
(blood)
- Blood Glucose
- Carcinoma, Renal Cell
(blood, drug therapy, mortality)
- Cholesterol
(blood)
- Disease-Free Survival
- Female
- Humans
- Kidney Neoplasms
(blood, drug therapy, mortality)
- Male
- Middle Aged
- Prognosis
- Sirolimus
(analogs & derivatives, therapeutic use)
- Triglycerides
(blood)
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