PMID- 22285181
OWN - NLM
STAT- MEDLINE
DCOM- 20120501
LR  - 20181201
IS  - 1879-0852 (Electronic)
IS  - 0959-8049 (Linking)
VI  - 48
IP  - 4
DP  - 2012 Mar
TI  - Phase I trial to investigate the safety, pharmacokinetics and efficacy of 
      sorafenib combined with docetaxel in patients with advanced refractory solid 
      tumours.
PG  - 465-74
LID - 10.1016/j.ejca.2011.12.026 [doi]
AB  - AIM: The safety, pharmacokinetics and efficacy of sorafenib plus docetaxel in 
      patients with advanced refractory cancer were investigated in a phase I, 
      dose-escalation trial. METHODS: Twenty-seven patients in four cohorts received 
      docetaxel on day 1 (cohorts 1 and 4: 75 mg/m2; cohorts 2 and 3: 100 mg/m2) plus 
      sorafenib on days 2-19 (cohorts 1 and 2: 200 mg twice-daily (bid); cohorts 3 and 
      4: 400 mg bid) in 21-day cycles. RESULTS: Most common adverse events (AEs) (grade 
      3-5) included neutropenia (89%), leucopaenia (81%), hand-foot skin reaction (30%) 
      and fatigue (30%). The most common drug-related AEs leading to dose 
      reduction/interruption or permanent discontinuation were dermatologic (41%), 
      gastrointestinal (26%) and constitutional (22%). Coadministration of sorafenib 
      altered the pharmacokinetics of docetaxel. On average, docetaxel area under the 
      concentration-time curve (AUC)(0-24) increased by 5% (cohort 1), 54% (cohort 2), 
      36% (Cohort 3) and 80% (cohort 4) with docetaxel plus sorafenib, while C(max) 
      increased by 16-32%, independent of sorafenib/docetaxel doses. Three of 25 
      evaluable patients (11%) had partial responses; 14 (52%) had stable disease. 
      CONCLUSION: Dose-limiting dermatologic AEs were more common than expected for 
      either therapy alone. A starting dose of docetaxel 75 mg/m2 plus sorafenib 400mg 
      bid (with dose reductions for dermatological toxicities) is proposed for phase 
      II.
CI  - Copyright A(c) 2012 Elsevier Ltd. All rights reserved.
FAU - Awada, Ahmad
AU  - Awada A
AD  - Jules Bordet Institute, Universite Libre de Bruxelles, Brussels, Belgium. 
      ahmad.awada@bordet.be
FAU - Hendlisz, Alain
AU  - Hendlisz A
FAU - Christensen, Olaf
AU  - Christensen O
FAU - Lathia, Chetan D
AU  - Lathia CD
FAU - Bartholomeus, Sylvie
AU  - Bartholomeus S
FAU - Lebrun, Fabienne
AU  - Lebrun F
FAU - de Valeriola, Dominique
AU  - de Valeriola D
FAU - Brendel, Erich
AU  - Brendel E
FAU - Radtke, Martin
AU  - Radtke M
FAU - Delaunoit, Thierry
AU  - Delaunoit T
FAU - Piccart-Gebhart, Martine
AU  - Piccart-Gebhart M
FAU - Gil, Thierry
AU  - Gil T
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120127
PL  - England
TA  - Eur J Cancer
JT  - European journal of cancer (Oxford, England : 1990)
JID - 9005373
RN  - 0 (Benzenesulfonates)
RN  - 0 (Phenylurea Compounds)
RN  - 0 (Pyridines)
RN  - 0 (Taxoids)
RN  - 15H5577CQD (Docetaxel)
RN  - 25X51I8RD4 (Niacinamide)
RN  - 9ZOQ3TZI87 (Sorafenib)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antineoplastic Combined Chemotherapy Protocols/administration & dosage/*adverse 
      effects/*pharmacokinetics/*therapeutic use
MH  - Benzenesulfonates/*administration & dosage/adverse effects/pharmacokinetics
MH  - Cohort Studies
MH  - Disease Progression
MH  - Docetaxel
MH  - Drug Administration Schedule
MH  - Drug Resistance, Neoplasm/drug effects
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Neoplasms/*drug therapy/pathology
MH  - Niacinamide/analogs & derivatives
MH  - Phenylurea Compounds
MH  - Pyridines/*administration & dosage/adverse effects/pharmacokinetics
MH  - Sorafenib
MH  - Taxoids/*administration & dosage/adverse effects/pharmacokinetics
MH  - Treatment Outcome
EDAT- 2012/01/31 06:00
MHDA- 2012/05/02 06:00
CRDT- 2012/01/31 06:00
PHST- 2011/04/18 00:00 [received]
PHST- 2011/12/20 00:00 [revised]
PHST- 2011/12/22 00:00 [accepted]
PHST- 2012/01/31 06:00 [entrez]
PHST- 2012/01/31 06:00 [pubmed]
PHST- 2012/05/02 06:00 [medline]
AID - S0959-8049(11)01075-6 [pii]
AID - 10.1016/j.ejca.2011.12.026 [doi]
PST - ppublish
SO  - Eur J Cancer. 2012 Mar;48(4):465-74. doi: 10.1016/j.ejca.2011.12.026. Epub 2012 
      Jan 27.