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- Title
Exposure-survival analyses of pazopanib in renal cell carcinoma and soft tissue sarcoma patients: opportunities for dose optimization.
- Authors
Verheijen, R.; Swart, L.; Beijnen, J.; Schellens, J.; Huitema, A.; Steeghs, N.; Verheijen, R B; Swart, L E; Beijnen, J H; Schellens, J H M; Huitema, A D R
- Abstract
<bold>Background: </bold>Pazopanib is an angiogenesis inhibitor approved for the treatment of renal cell carcinoma and soft tissue sarcoma. Post hoc analysis of a clinical trial demonstrated a relationship between pazopanib trough concentrations (Cmin) and treatment efficacy. The aim of this study was to explore the pharmacokinetics and exposure-survival relationships of pazopanib in a real-world patient cohort.<bold>Patients and Methods: </bold>Renal cell cancer and soft tissue sarcoma patients who had at least one pazopanib plasma concentration available were included. Using calculated Cmin values and a threshold of > 20 mg/L, univariate and multivariate exposure-survival analyses were performed.<bold>Results: </bold>Sixty-one patients were included, of which 16.4% were underexposed (mean Cmin < 20 mg/L) using the 800 mg fixed-dosed schedule. In univariate analysis Cmin > 20 mg/L was related to longer progression free survival in renal cell cancer patients (34.1 vs. 12.5 weeks, n = 35, p = 0.027) and the overall population (25.0 vs. 8.8 weeks, n = 61, p = 0.012), but not in the sarcoma subgroup (18.7 vs. 8.8 weeks, n = 26, p = 0.142). In multivariate analysis Cmin > 20 mg/L was associated with hazard ratios of 0.25 (p = 0.021) in renal cancer, 0.12 (p = 0.011) in sarcoma and 0.38 (p = 0.017) in a pooled analysis.<bold>Conclusion: </bold>This study confirms that pazopanib Cmin > 20 mg/L relates to better progression free survival in renal cancer and points towards a similar trend in sarcoma patients. Cmin monitoring of pazopanib can help identify patients with low Cmin for whom individualized treatment at a higher dose may be appropriate.
- Subjects
CANCER treatment; RENAL cell carcinoma; NEOVASCULARIZATION inhibitors; DRUG efficacy; SARCOMA; PATIENTS; HETEROCYCLIC compounds; SULFONAMIDES; SURVIVAL analysis (Biometry); TREATMENT effectiveness; THERAPEUTICS
- Publication
Cancer Chemotherapy & Pharmacology, 2017, Vol 80, Issue 6, p1171
- ISSN
0344-5704
- Publication type
journal article
- DOI
10.1007/s00280-017-3463-x