PMID- 25252180
OWN - NLM
STAT- MEDLINE
DCOM- 20160425
LR  - 20181202
IS  - 1464-410X (Electronic)
IS  - 1464-4096 (Linking)
VI  - 117
IP  - 1
DP  - 2016 Jan
TI  - Sunitinib-induced hypertension, neutropaenia and thrombocytopaenia as predictors 
      of good prognosis in patients with metastatic renal cell carcinoma.
PG  - 110-7
LID - 10.1111/bju.12940 [doi]
AB  - OBJECTIVES: 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). 
      PATIENTS AND 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). CONCLUSION: 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.
CI  - (c) 2014 The Authors BJU International (c) 2014 BJU International Published by John 
      Wiley & Sons Ltd.
FAU - Rautiola, Juhana
AU  - Rautiola J
AD  - Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland.
AD  - Laboratory of Molecular Oncology, Molecular Cancer Biology Research Program, 
      Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.
FAU - Donskov, Frede
AU  - Donskov F
AD  - Department of Oncology, Aarhus University Hospital, Aarhus, Denmark.
FAU - Peltola, Katriina
AU  - Peltola K
AD  - Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland.
FAU - Joensuu, Heikki
AU  - Joensuu H
AD  - Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland.
AD  - Laboratory of Molecular Oncology, Molecular Cancer Biology Research Program, 
      Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.
FAU - Bono, Petri
AU  - Bono P
AD  - Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland.
AD  - Laboratory of Molecular Oncology, Molecular Cancer Biology Research Program, 
      Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.
LA  - eng
PT  - Journal Article
DEP - 20150602
PL  - England
TA  - BJU Int
JT  - BJU international
JID - 100886721
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Biomarkers)
RN  - 0 (Indoles)
RN  - 0 (Pyrroles)
RN  - V99T50803M (Sunitinib)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Agents/administration & dosage/*adverse effects/therapeutic use
MH  - Biomarkers
MH  - Carcinoma, Renal Cell/*drug therapy/epidemiology/mortality
MH  - Female
MH  - Humans
MH  - Hypertension/*chemically induced/epidemiology
MH  - Indoles/administration & dosage/*adverse effects/therapeutic use
MH  - Kaplan-Meier Estimate
MH  - Kidney Neoplasms/*drug therapy/epidemiology/mortality
MH  - Male
MH  - Middle Aged
MH  - Neutropenia/*chemically induced/epidemiology
MH  - Prognosis
MH  - Pyrroles/administration & dosage/*adverse effects/therapeutic use
MH  - Retrospective Studies
MH  - Sunitinib
MH  - Thrombocytopenia/*chemically induced/epidemiology
MH  - Treatment Outcome
OTO - NOTNLM
OT  - angiogenesis
OT  - biomarkers
OT  - renal cell carcinoma
OT  - sunitinib
OT  - tyrosine kinase inhibitor
EDAT- 2014/09/25 06:00
MHDA- 2016/04/26 06:00
CRDT- 2014/09/25 06:00
PHST- 2014/09/25 06:00 [entrez]
PHST- 2014/09/25 06:00 [pubmed]
PHST- 2016/04/26 06:00 [medline]
AID - 10.1111/bju.12940 [doi]
PST - ppublish
SO  - BJU Int. 2016 Jan;117(1):110-7. doi: 10.1111/bju.12940. Epub 2015 Jun 2.