An indirect comparison of the toxicity of sunitinib and pazopanib in metastatic clear cell renal cancer

被引:13
|
作者
Powles, Thomas [1 ]
Sarwar, Naveed [1 ]
Jones, Rob [2 ]
Wilson, Peter [1 ]
Boleti, Ekaterini [3 ]
Protheroe, Andrew [4 ]
Crabb, Simon J. [5 ]
Shamash, Jonathan [1 ]
Stockdale, Andrew [6 ,7 ]
Rashid, Sukaina [1 ]
Nathan, Paul [8 ]
Chowdury, Simon [9 ]
机构
[1] Queen Mary Univ, Barts Canc Inst, Expt Canc Med Ctr, London, England
[2] Beatson Hosp, Dept Med Oncol, Glasgow, Lanark, Scotland
[3] Royal Free Hosp, Dept Med Oncol, London NW3 2QG, England
[4] John Radcliffe Hosp, Dept Med Oncol, London, England
[5] Univ Southampton, Dept Med Oncol, Southampton, Hants, England
[6] Univ Hosp Coventry, Dept Oncol, Coventry, W Midlands, England
[7] Warwickshire NHS Trust, Warwick, England
[8] Mt Vernon Hosp, Dept Oncol, London, England
[9] Guys & St Thomas Hosp, London SE1 9RT, England
关键词
Sunitinib; Pazopanib; Metastatic renal cancer; Toxicity; CARCINOMA; TRIAL;
D O I
10.1016/j.ejca.2012.05.022
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Both sunitinib and pazopanib are widely used as first line therapy in metastatic renal cancer (mRCC). The efficacy of these agents appears similar but they may have distinct toxicity profiles. In this study we compare the severity of symptomatic and asymptomatic toxicity associated with sunitinib and pazopanib. Methods: Two sequential prospective single arm phase II studies investigated either 12 weeks of sunitinib (n = 43) or pazopanib (n = 34) prior to nephrectomy in untreated mRCC. Toxicity was defined as either symptomatic (hand and foot syndrome, mucositis, nausea, fatigue, diarrhoea, oedema, headache, pain, anorexia and change in taste) or asymptomatic (liver toxicity or haematological toxicity). Pazopanib (800 mg once daily (OD)) and sunitinib (50 mg 4/2) were given. Regular Common Toxicity Criteria (CTC) toxicity assessment was performed during the first 12 weeks of therapy. Results: There was no significant difference in the overall number of toxic events (grade 1-4) for sunitinib and pazopanib (mean number of toxic events/patients: 1.97 versus 1.96: p > 0.05). Increased grade 2-4 symptomatic toxicity events occurred with sunitinib (hazard ratio (HR) 1.67 [95% confidence interval (CI): 1.11-2.56] p < 0.03). Sunitinib was associated with an increased grade 2-4 mucositis (16% versus 0% p = 0.02) and fatigue (42% versus 15% p = 0.01). Pazopanib was associated with more frequent grade 1 diarrhoea (39% versus 12%: p = 0.03). Dose reductions for symptomatic toxicity occurred more frequently with sunitinib (26% versus 6% p < 0.05). There was no difference in the occurrence of asymptomatic toxicity. Conclusion: This indirect analysis suggests sunitinib and pazopanib have distinct toxicity profiles which may help guide patient's choice. Further comparative data from randomised trials are awaited. (C) 2012 Elsevier Ltd. All rights reserved.
引用
收藏
页码:3171 / 3176
页数:6
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