Role of sunitinib and SU12662 on dermatological toxicities in metastatic renal cell carcinoma patients: in vitro, in vivo, and outcomes investigation
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- 作者：Yi Ling Teo (1) (2)
Xue Jing Chong (1)
Xiu Ping Chue (1)
Noan Minh Chau (3)
Min-Han Tan (3)
Ravindran Kanesvaran (3)
Hwee Lin Wee (1)
Han Kiat Ho (1)
Alexandre Chan (1) (2) - 关键词：Sunitinib ; SU12662 ; Metastatic renal cell carcinoma ; Dermatological toxicity ; HRQoL
- 刊名：Cancer Chemotherapy and Pharmacology
- 出版年：2014
- 出版时间：February 2014
- 年：2014
- 卷：73
- 期：2
- 页码：381-388
- 全文大小：381 KB
- 作者单位：Yi Ling Teo (1) (2)
Xue Jing Chong (1)
Xiu Ping Chue (1)
Noan Minh Chau (3)
Min-Han Tan (3)
Ravindran Kanesvaran (3)
Hwee Lin Wee (1)
Han Kiat Ho (1)
Alexandre Chan (1) (2)
1. Department of Pharmacy, Faculty of Science, National University of Singapore, 18 Science Drive 4, Singapore, 117543, Singapore
2. Department of Pharmacy, National Cancer Centre Singapore, Singapore, Singapore
3. Department of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore - ISSN：1432-0843
文摘
Purpose Sunitinib commonly exhibits dose-limiting dermatological toxicities (DTs) that adversely affect health-related quality of life (HRQoL). Pharmacological activity of sunitinib is attributed to sunitinib and an equipotent, active metabolite, SU12662. The objective of this study is to compare the dermatotoxic potential of sunitinib and SU12662, and changes in HRQoL due to DTs. Methods A prospective cohort study was conducted on metastatic renal cell carcinoma patients. Plasma drug concentrations were determined by high-performance liquid chromatography. DTs were graded by Common Terminology Criteria for Adverse Events. HRQoL of patients with hand–foot skin reaction (HFSR) was assessed by the hand–foot syndrome-specific quality-of-life questionnaire (HFS-14). In addition, the IC50s of both compounds were determined with HaCaT keratinocytes. Results Sunitinib was more dermatotoxic in vitro, with a lower IC50 than SU12662 (23.33 vs. 35.32?μM, p?=?0.02). Similar results were observed in vivo, with higher sunitinib-to-SU12662 ratio in patients with pruritus, than patients without pruritus (p?=?0.04). Higher HFS-14 scores were observed in patients with higher HFSR grade and in those with both hands and feet affected, indicating poorer HRQoL. Conclusions Sunitinib may be more dermatotoxic than SU12662 from both in vivo and in vitro evidences. Therefore, appropriate management of DTs may be essential, especially in patients with a reduced sunitinib metabolising ability.