Characterization of hyperglycemia, hypercholesterolemia, and hyperlipidemia in patients with advanced renal cell carcinoma treated with temsirolimus or interferon-α
Authors: P. L. de Souza, S. Radulovic, J. Beck, K. Pendergrass, N. Siddique, J. P. Dutcher, A. Berkenblit, A. Thiele, M. Krygowski, G. R. Hudes
Journal: Journal of Clinical Oncology (2008)

5116 Background: Temsirolimus (TEMSR), an inhibitor of mTOR has been approved in the US for treatment of patients (pts) with advanced renal cell carcinoma (RCC) and in Europe (for RCC pts with 3 prognostic risk factors). Hyperglycemia (HG), hypercholesterolemia (HC), and hyperlipidemia (HL) were significant adverse events observed in RCC pts treated with TEMSR vs interferon-α (IFN; Hudes et al. N Engl J Med 2007; 356: 2271–81). In exploratory analyses, HG was examined in RCC pts treated with TEMSR or IFN in 2 separate subsets, diabetic and non-diabetic. HL and HC were characterized in pts treated with TEMSR or IFN. Methods: Pts in the IFN group received 3 million units (MU) subcutaneously 3x weekly, escalating to 18 MU. Pts in the TEMSR group received 25 mg IV weekly. An unstratified Cox proportional hazards model was used to analyze overall survival (OS) and progression-free survival (PFS). Fisher’s exact test was used to test association between treatment and development of HG, HC and HL. Results: TEMSR was associated with the development of HG in RCC pts with and without a history of diabetes (p=0.001 in non-diabetic pts, p=0.002 in diabetic pts; Table); 16% of non-diabetic pts in the TEMSR arm developed ≥gr 2 HG, compared with 3% in the IFN arm. All diabetic pts in the TEMSR arm developed ≥gr 2 HG compared with 36% in the IFN arm. TEMSR was also associated with the development of ≥gr 2 HC compared with IFN (p=0.001) but not with the development of gr 2 HL (p=0.675). When pts treated with TEMSR vs IFN were compared, there was no evidence of interaction between treatment and HG or HC for OS (HG, p=0.115; HC, p=0.453) or PFS (independent assessment, HG, p=0.739; HC, p=0.227). Conclusions: Compared to IFN, TEMSR treated pts are more likely to develop ≥gr 2 HG and HC, and may require medical management. For OS and PFS, no interaction was detected between HG or HC and treatment. Number of patients, median onset and duration of HG, HL and HC n (%) a IFN (N=207) TEMSR (N=209) P-Value Median Onset, d (range) Median Duration, d (range) n (%) a Median Onset, d (range) Median Duration, d (range) ≥ Grade 2 HG Non-diabetic 0.001 No 105 (97) 102 (84) Yes 3 (3) 58 (15–394) 15 (1–29) 19 (16) 92 (15–382) 15 (1–95) Diabetic 0.002 No 9 (64) 0 (0) Yes 5 (36) 57 (14–76) 28 (20–114) 10 (100) 15 (14–29) 28 (15–155) ≥ Grade 2 HL 0.675 No 173 (95) 191 (93) Yes 10 (6) 60 (28–170) 15 (9–99) 14 (7) 71 (17–394) 15 (8–127) ≥ Grade 2 HC 0.001 No 179 (99) 189 (92) Yes 2 (1) 28.5 (28–29) 71 (71–71) 17 (8) 69 (29–253) 15 (14–141) a : % is representative of those with ≥ Grade 2 HG, HL or HC Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Wyeth Pharmaceuticals Wyeth Pharmaceuticals Wyeth Pharmaceuticals Wyeth Pharmaceuticals Wyeth Pharmaceuticals