title: An indirect comparison of the toxicity of sunitinib and pazopanib in metastatic clear cell renal cancer.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors: Experimental Cancer Medicine Centre, Barts Cancer Institute, Queen Mary University of London, London, UK. thomas.powles@bartshealth.nhs.uk
authors: Thomas
authors: T
authors: Powles
authors: Naveed
authors: N
authors: Sarwar
authors: Rob
authors: R
authors: Jones
authors: Peter
authors: P
authors: Wilson
authors: Ekaterini
authors: E
authors: Boleti
authors: Andrew
authors: A
authors: Protheroe
authors: Simon J
authors: SJ
authors: Crabb
authors: Jonathan
authors: J
authors: Shamash
authors: Andrew
authors: A
authors: Stockdale
authors: Sukaina
authors: S
authors: Rashid
authors: Paul
authors: P
authors: Nathan
authors: Simon
authors: S
authors: Chowdury
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology*; D005260:Female; D006801:Humans; D007191:Indazoles; D007211:Indoles / Q000009:adverse effects*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy; D011446:Prospective Studies; D011743:Pyrimidines / Q000009:adverse effects*; D011758:Pyrroles / Q000009:adverse effects*; D013449:Sulfonamides / Q000009:adverse effects*; D000077210:Sunitinib
chemical_list: D000970:Antineoplastic Agents; D007191:Indazoles; D007211:Indoles; D011743:Pyrimidines; D011758:Pyrroles; D013449:Sulfonamides; C516667:pazopanib; D000077210:Sunitinib