title: Sunitinib-induced hypertension, neutropaenia and thrombocytopaenia as predictors of good prognosis in patients with metastatic renal cell carcinoma.
abstract: OBJECTIVE
  To evaluate the clinical significance of hypertension (HTN), neutropaenia and thrombocytopaenia as possible new biomarkers of sunitinib efficacy in non-trial patients with metastatic renal cell carcinoma (mRCC).
  
  
  METHODS
  In all, 181 consecutive patients with mRCC were treated with sunitinib; 39 (22%) received sunitinib 50 mg/day 4 weeks on/2 weeks off, 80 (44%) received 37.5 mg/day continuously and 62 (34%) received 25 mg/day continuously as their starting dose. Treatment-induced adverse events (AEs) and their impact on outcome were analysed on multiple sunitinib doses.
  
  
  RESULTS
  During sunitinib treatment 60 patients (33%) developed ≥grade 2 HTN, 88 (49%) ≥grade 2 neutropaenia and 135 (75%) ≥grade 1 thrombocytopaenia. These AEs were associated significantly with longer progression-free survival (PFS; 15.7 vs 6.7; 14.6 vs 6.9; 10.4 vs 4.2 months, respectively; P < 0.001) and overall survival (OS; 37.5 vs 16.2; 33.7 vs 13.2; 22.3 vs 13.2 months, respectively, P ≤ 0.008). Although only neutropaenia was associated with a significantly improved PFS and OS in all sunitinib doses, a similar trend was also seen with HTN and thrombocytopaenia in all sunitinib doses. In multivariate analysis, HTN and neutropaenia were significantly associated with PFS and OS and thrombocytopaenia was significantly associated with PFS. In a 12-week landmark analysis, HTN and thrombocytopaenia were significantly associated with PFS and OS. Patients who developed all three AEs (a favourable biomarker profile) had significantly better outcome than patients without these AEs (a poor biomarker profile); response rate 47% vs 4%, median PFS 27.1 vs 3.5 months and OS not reached vs 5.3 months (all P < 0.001).
  
  
  CONCLUSIONS
  HTN, neutropaenia and thrombocytopaenia were all biomarkers of sunitinib efficacy in patients with mRCC. Our results may help to individualise sunitinib dosing during therapy based on these common sunitinib-related AEs.
authors.affiliation: Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland.|Laboratory of Molecular Oncology, Molecular Cancer Biology Research Program, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.
authors.forename: Juhana
authors.initials: J
authors.lastname: Rautiola
authors.affiliation: Department of Oncology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Frede
authors.initials: F
authors.lastname: Donskov
authors.affiliation: Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Katriina
authors.initials: K
authors.lastname: Peltola
authors.affiliation: Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland.|Laboratory of Molecular Oncology, Molecular Cancer Biology Research Program, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.
authors.forename: Heikki
authors.initials: H
authors.lastname: Joensuu
authors.affiliation: Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland.|Laboratory of Molecular Oncology, Molecular Cancer Biology Research Program, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.
authors.forename: Petri
authors.initials: P
authors.lastname: Bono
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D015415:Biomarkers; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000453:epidemiology / Q000401:mortality; D005260:Female; D006801:Humans; D006973:Hypertension / Q000139:chemically induced* / Q000453:epidemiology; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000453:epidemiology / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced* / Q000453:epidemiology; D011379:Prognosis; D011758:Pyrroles / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D012189:Retrospective Studies; D000077210:Sunitinib; D013921:Thrombocytopenia / Q000139:chemically induced* / Q000453:epidemiology; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib
keywords: angiogenesis; biomarkers; renal cell carcinoma; sunitinib; tyrosine kinase inhibitor