PMID- 27981711
OWN - NLM
STAT- MEDLINE
DCOM- 20170630
LR  - 20181202
IS  - 1464-410X (Electronic)
IS  - 1464-4096 (Linking)
VI  - 119
IP  - 6
DP  - 2017 Jun
TI  - Sorafenib dose escalation in treatment-naive patients with metastatic renal cell 
      carcinoma: a non-randomised, open-label, Phase 2b study.
PG  - 846-853
LID - 10.1111/bju.13740 [doi]
AB  - OBJECTIVE: To assess the efficacy and safety of sorafenib dose escalation in 
      metastatic renal cell carcinoma (mRCC). PATIENTS AND METHODS: Intra-patient dose 
      escalation may enhance the clinical benefit of targeted anticancer agents in 
      metastatic disease. In this non-randomised, open-label, Phase 2b study, 
      treatment-naive patients with mRCC were initially treated with the standard oral 
      sorafenib dose [400 mg twice daily (BID)]. Two dose escalations were planned, 
      each 200 mg BID after 28 days at the prior level. Dose reductions, interruptions, 
      or delayed escalations were used to manage adverse events (AEs). The primary 
      endpoint was objective response rate (ORR) in the modified intent-to-treat (mITT) 
      population, which comprised patients with >/=6 months of treatment including >/=4 
      months of therapy at their highest tolerated dose. Secondary endpoints included 
      progression-free survival (PFS) and safety. RESULTS: In all, 83 patients received 
      sorafenib. The dose received for the longest duration was 400, 600, and 800 mg 
      BID in 48.2%, 15.7%, and 24.1% of patients, respectively. The ORR was 44.4% [n = 
      8/18; 95% confidence interval (CI) 21.5-69.2] and 17.9% (n = 12/67; 95% CI 
      9.6-29.2) in the mITT and ITT populations, respectively. The median (95% CI) PFS 
      was 7.4 (6.0-11.7) months (ITT). The most common AEs of any grade were hand-foot 
      skin reaction (66.3%) and diarrhoea (63.9%). CONCLUSION: Sorafenib demonstrated 
      clinical benefit in treatment-naive patients with mRCC. However, relatively few 
      patients could sustain doses of >400 mg BID. There was evidence that, where 
      tolerated, escalation from the standard sorafenib dose may have enhanced clinical 
      benefit. However, this study does not support dose escalation for most patients 
      with treatment-naive mRCC. Alternative protocols for sorafenib dose escalation 
      could be explored.
CI  - (c) 2016 The Authors BJU International (c) 2016 BJU International Published by John 
      Wiley & Sons Ltd.
FAU - Gore, Martin E
AU  - Gore ME
AD  - Royal Marsden Hospital, London, UK.
FAU - Jones, Robert J
AU  - Jones RJ
AD  - Beatson West of Scotland Cancer Centre, University of Glasgow, Glasgow, UK.
FAU - Ravaud, Alain
AU  - Ravaud A
AD  - Hopital Saint-Andre CHU, Bordeaux, France.
FAU - Kuczyk, Markus
AU  - Kuczyk M
AD  - Medizinische Hochschule Hannover, Hannover, Germany.
FAU - Demkow, Tomasz
AU  - Demkow T
AD  - Bayer Vital GmbH, Leverkusen, Germany.
FAU - Bearz, Alessandra
AU  - Bearz A
AD  - Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie, Warszawa, Poland.
FAU - Shapiro, JoAnn
AU  - Shapiro J
AD  - IRCCS Centro Rif Oncologico, Aviano, Italy.
FAU - Strauss, Uwe Phillip
AU  - Strauss UP
AD  - IRCCS Policlinico San Matteo, Medicina Interna ed Oncologia Medica, Pavia, Italy.
FAU - Porta, Camillo
AU  - Porta C
AD  - Bayer HealthCare Pharmaceuticals Inc., Whippany, NJ, USA.
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
DEP - 20170109
PL  - England
TA  - BJU Int
JT  - BJU international
JID - 100886721
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Phenylurea Compounds)
RN  - 25X51I8RD4 (Niacinamide)
RN  - 9ZOQ3TZI87 (Sorafenib)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Agents/*administration & dosage
MH  - Carcinoma, Renal Cell/*drug therapy/*secondary
MH  - Disease-Free Survival
MH  - Female
MH  - Humans
MH  - Kidney Neoplasms/*drug therapy/pathology
MH  - Male
MH  - Middle Aged
MH  - Niacinamide/administration & dosage/*analogs & derivatives
MH  - Phenylurea Compounds/*administration & dosage
MH  - Research Design
MH  - Sorafenib
MH  - Treatment Outcome
OTO - NOTNLM
OT  - #KidneyCancer
OT  - dose escalation
OT  - renal cell carcinoma
OT  - sorafenib
OT  - targeted therapy
OT  - tyrosine kinase inhibitor
EDAT- 2016/12/17 06:00
MHDA- 2017/07/01 06:00
CRDT- 2016/12/17 06:00
PHST- 2016/12/17 06:00 [pubmed]
PHST- 2017/07/01 06:00 [medline]
PHST- 2016/12/17 06:00 [entrez]
AID - 10.1111/bju.13740 [doi]
PST - ppublish
SO  - BJU Int. 2017 Jun;119(6):846-853. doi: 10.1111/bju.13740. Epub 2017 Jan 9.