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Association of drug exposure with toxicity and clinical response in metastatic renal cell carcinoma patients receiving an attenuated dosing regimen of sunitinib

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Abstract

An attenuated dosing (AD) regimen of 37.5 mg daily in repeated 4 week on, 2 week off cycles has been proposed to ameliorate frequent dose modifications caused by the toxicity observed with the approved dosing regimen of sunitinib for metastatic renal cell carcinoma (mRCC). This study aimed to determine the effect of drug exposure on toxicity and clinical response in patients receiving this regimen. All mRCC patients receiving AD sunitinib were invited to participate. In week 4 of each cycle, toxicity and plasma levels were assessed. Clinical responses were assessed after two cycles. A total of 36 patients were recruited. Patients who manifested ≥grade 2 mucositis (126.46 vs 84.81 ng/mL, p = 0.04) and altered taste (159.91 vs 105.22 ng/mL, p = 0.05) had higher total exposure than those who had grade 1 or no toxicity. Twenty-six patients completed two treatment cycles; four (15 %) had partial responses, 15 (58 %) had a stable disease and 7 (27 %) had progressive disease. No difference in the exposure levels was found among the patients with different clinical outcomes. The AD regimen of sunitinib in Asian mRCC patients provided sufficient drug exposure with a lower incidence of toxicity, with higher drug exposure being observed in patients who experienced toxicity.

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Acknowledgments

The authors would like to acknowledge the Singapore Cancer Society for the provision of grant support for this work.

Conflicts of interest

Drs Kanesvaran, Wee, and Chan serve as consultants to GlaxoSmithKline (Kanesvaran and Chan), Merck Sharp & Dohme (Chan), Pfizer (Wee), Novartis Asia Pacific (Wee), and Abbvie Pte Ltd (Wee). All remaining authors have declared no conflicts of interest.

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Authors and Affiliations

  1. Department of Pharmacy, Faculty of Science, National University of Singapore, 18 Science Drive 4, Singapore, 117543, Singapore

    Yi Ling Teo, Xiu Ping Chue, Hwee Lin Wee, Han Kiat Ho & Alexandre Chan

  2. Department of Medical Oncology, National Cancer Centre Singapore, 11 Hospital Drive, Singapore, 169610, Singapore

    Noan Minh Chau, Min-Han Tan & Ravindran Kanesvaran

  3. Department of Pharmacy, National Cancer Centre Singapore, 11 Hospital Drive, Singapore, 169610, Singapore

    Alexandre Chan

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  1. Yi Ling Teo
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Correspondence to Alexandre Chan.

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Teo, Y.L., Chue, X.P., Chau, N.M. et al. Association of drug exposure with toxicity and clinical response in metastatic renal cell carcinoma patients receiving an attenuated dosing regimen of sunitinib. Targ Oncol 10, 429–437 (2015). https://doi.org/10.1007/s11523-014-0349-2

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  • DOI: https://doi.org/10.1007/s11523-014-0349-2

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