Powles, Thomas, Sarwar, Naveed, Jones, Rob, Wilson, Peter, Boleti, Ekaterini, Protheroe, Andrew, Crabb, Simon J, Shamash, Jonathan, Stockdale, Andrew, Rashid, Sukaina, Nathan, Paul and Chowdury, Simon
An indirect comparison of the toxicity of sunitinib and pazopanib in metastatic clear cell renal cancer.
European Journal of Cancer (doi:10.1016/j.ejca.2012.05.022). (PMID:22766517).
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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 12weeks 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 (800mg once daily (OD)) and sunitinib (50mg 4/2) were given. Regular Common Toxicity Criteria (CTC) toxicity assessment was performed during the first 12weeks 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.
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