title: Angiotensin Inhibitors as Treatment of Sunitinib/Pazopanib-induced Hypertension in Metastatic Renal Cell Carcinoma.
abstract: Research suggests that baseline use of angiotensin system inhibitors (ASIs) improves outcome in patients with metastatic renal cell carcinoma (mRCC), but it remains unknown whether the type of antihypertensive medication used to initiate management at onset of treatment-induced hypertension (HTN) is associated with outcome. We evaluated the association of ASIs and outcome among patients with mRCC treated with first-line tyrosine kinase inhibitors (TKIs).
  
  
  
  We identified 303 consecutive patients with mRCC who were treated with sunitinib or pazopanib in a single university hospital cancer center. Statistical analyses were performed using the Kaplan-Meier method and Cox regression adjusted for known risk factors.
  
  
  
  Progression-free survival (PFS) and overall survival (OS) were similar among patients with baseline HTN (n = 197; 65%) versus patients with no baseline HTN (n = 106; 35%) (PFS; P = .72) (OS; P = .54). There was a significant difference between patients with treatment-induced HTN (n = 110) versus patients with no treatment-induced HTN (n = 193) for PFS (15.6 vs. 6.4 months, respectively; P < .001) and OS (34.9 vs. 13.9 months, respectively; P < .001). Use of ASIs at baseline (n = 126; 41.6%) had no impact on outcome as compared with patients receiving other antihypertensive medication (n = 71; 23.4%) or with patients with no baseline antihypertensive medication (n = 106; 35.0%). Among patients with TKI-induced HTN (n = 110), however, ASI users (n = 91) demonstrated improved OS (37.5 vs. 18.1 months; P = .001) and PFS (17.1 vs. 7.2 months; P = .004) versus ASI nonusers (n = 19), respectively.
  
  
  
  Our results demonstrate survival benefit for ASI users among patients with TKI-induced HTN. These results, however, require further validation in a prospective setting.
authors.affiliation: Comprehensive Cancer Center, Helsinki University Central Hospital, Helsinki, Finland. Electronic address: patrick.penttila@helsinki.fi.
authors.forename: Patrick
authors.initials: P
authors.lastname: Penttilä
authors.affiliation: Comprehensive Cancer Center, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Juhana
authors.initials: J
authors.lastname: Rautiola
authors.affiliation: STAT-Consulting, Nokia, Finland.
authors.forename: Tuija
authors.initials: T
authors.lastname: Poussa
authors.affiliation: Comprehensive Cancer Center, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Katriina
authors.initials: K
authors.lastname: Peltola
authors.affiliation: Comprehensive Cancer Center, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Petri
authors.initials: P
authors.lastname: Bono
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy*; D007191:Indazoles; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects; D007680:Kidney Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects; D011758:Pyrroles / Q000008:administration & dosage / Q000009:adverse effects; D012189:Retrospective Studies; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects; D000077210:Sunitinib; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D020533:Angiogenesis Inhibitors; D000806:Angiotensin-Converting Enzyme Inhibitors; D007191:Indazoles; D007211:Indoles; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; D013449:Sulfonamides; C516667:pazopanib; D000077210:Sunitinib
keywords: Angiogenesis; Angiotensin system inhibitors; Hypertension; Renal cancer; Tyrosine kinase inhibitors