PMID- 16724239
OWN - NLM
STAT- MEDLINE
DCOM- 20070423
LR  - 20181201
IS  - 0344-5704 (Print)
IS  - 0344-5704 (Linking)
VI  - 59
IP  - 2
DP  - 2007 Feb
TI  - Sorafenib is efficacious and tolerated in combination with cytotoxic or 
      cytostatic agents in preclinical models of human non-small cell lung carcinoma.
PG  - 183-95
AB  - PURPOSE: Sorafenib tosylate (sorafenib, BAY 43-9006, Nexavar) is a multi-kinase 
      inhibitor that targets tumor cell proliferation and angiogenesis. These studies 
      evaluated the efficacy and tolerability of combinations of sorafenib plus agents 
      used to treat non-small cell lung cancer (NSCLC) using preclinical models of that 
      disease. METHODS: Intravenous (iv) vinorelbine and interperitoneal (ip) cisplatin 
      were administered intermittently (q4d x 3) in combination with sorafenib 
      administered orally (po) once daily for 9 days starting on the same day as the 
      standard agent. In studies with sorafenib and gefitinib, both agents were 
      administered po daily for 10 days starting on the same day. Treatment in all 
      studies was initiated against established sc tumors, and each study was conducted 
      in duplicate. Efficacy was assessed as the delay in tumor growth to a specified 
      size (TGD). RESULTS: Vinorelbine (6.7 mg/kg) and sorafenib (40 mg/kg) produced 
      TGDs of 2.4 and 7.8 days, respectively, in the NCI-H460 NSCLC model. Combination 
      therapy produced a 10.0-day TGD with no increase in toxicity. Combination therapy 
      in the NCI-H23 NSCLC model with the highest evaluated dose levels of sorafenib 
      plus cisplatin was well tolerated and produced TGDs equivalent to those produced 
      by cisplatin alone. Lower dose levels of each agent produced approximately 
      additive TGD's. Combination therapy in the A549 NSCLC model with sorafenib and 
      gefitinib produced TGDs equivalent to that produced by sorafenib alone with no 
      toxicity. Tumor growth in the MDA-MB-231 mammary tumor model, that contains 
      mutations in signal transduction proteins downstream of the EGF receptor (the 
      target of gefitinib) was also inhibited by sorafenib, but not by gefitinib. 
      CONCLUSION: Concurrent administration of sorafenib and vinorelbine, cisplatin or 
      gefitinib was at least as efficacious as the individual agents alone and was well 
      tolerated. These results support the inclusion of sorafenib in clinical trials in 
      NSCLC employing combinations of both cytotoxic and cytostatic agents.
FAU - Carter, Christopher A
AU  - Carter CA
AD  - Bayer Pharmaceuticals Corporation, West Haven, CT 06516, USA. 
      christopher.carter.b@bayer.com
FAU - Chen, Charles
AU  - Chen C
FAU - Brink, Cheryl
AU  - Brink C
FAU - Vincent, Patrick
AU  - Vincent P
FAU - Maxuitenko, Yulia Y
AU  - Maxuitenko YY
FAU - Gilbert, Karen S
AU  - Gilbert KS
FAU - Waud, William R
AU  - Waud WR
FAU - Zhang, Xiaomei
AU  - Zhang X
LA  - eng
PT  - Journal Article
DEP - 20060525
PL  - Germany
TA  - Cancer Chemother Pharmacol
JT  - Cancer chemotherapy and pharmacology
JID - 7806519
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Benzenesulfonates)
RN  - 0 (Cytotoxins)
RN  - 0 (Phenylurea Compounds)
RN  - 0 (Pyridines)
RN  - 0 (Quinazolines)
RN  - 25X51I8RD4 (Niacinamide)
RN  - 5V9KLZ54CY (Vinblastine)
RN  - 9ZOQ3TZI87 (Sorafenib)
RN  - Q20Q21Q62J (Cisplatin)
RN  - Q6C979R91Y (Vinorelbine)
RN  - S65743JHBS (Gefitinib)
SB  - IM
MH  - Administration, Oral
MH  - Animals
MH  - Antineoplastic Agents/administration & dosage
MH  - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
MH  - Benzenesulfonates/administration & dosage
MH  - Carcinoma, Non-Small-Cell Lung/*drug therapy/pathology
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Cisplatin/pharmacology
MH  - Cytotoxins/administration & dosage
MH  - Dose-Response Relationship, Drug
MH  - Drug Administration Schedule
MH  - Female
MH  - Gefitinib
MH  - Humans
MH  - Lung Neoplasms/*drug therapy/pathology
MH  - Mice
MH  - Mice, Nude
MH  - Niacinamide/analogs & derivatives
MH  - Phenylurea Compounds
MH  - Pyridines/administration & dosage
MH  - Quinazolines/pharmacology
MH  - Sorafenib
MH  - Vinblastine/analogs & derivatives/pharmacology/therapeutic use
MH  - Vinorelbine
MH  - Weight Loss/drug effects
MH  - Xenograft Model Antitumor Assays/*methods
EDAT- 2006/05/26 09:00
MHDA- 2007/04/24 09:00
CRDT- 2006/05/26 09:00
PHST- 2006/04/22 00:00 [received]
PHST- 2006/04/23 00:00 [accepted]
PHST- 2006/05/26 09:00 [pubmed]
PHST- 2007/04/24 09:00 [medline]
PHST- 2006/05/26 09:00 [entrez]
AID - 10.1007/s00280-006-0257-y [doi]
PST - ppublish
SO  - Cancer Chemother Pharmacol. 2007 Feb;59(2):183-95. doi: 
      10.1007/s00280-006-0257-y. Epub 2006 May 25.