Sorafenib tosylate and paclitaxel induce anti-angiogenic, anti-tumour and anti-resorptive effects in experimental breast cancer bone metastases.
OBJECTIVE
In this study we investigated sorafenib tosylate and paclitaxel as single and combination therapies regarding their effects on tumour growth and vasculature as well as their potency to inhibit osteolysis in experimental breast cancer bone metastases.


METHODS
Nude rats bearing breast cancer bone metastases were treated with sorafenib tosylate (7 mg/kg, n=11), paclitaxel (5mg/kg, n=11) or the combination of both (n=10) and were compared to untreated controls (n=11). In a longitudinal study, volumes of osteolyses and respective soft tissue tumours were measured in these groups by MRI and volume CT, while changes in cellularity within bone metastases were assessed by diffusion-weighted imaging. Dynamic contrast-enhanced MRI and vessel size imaging was performed to determine changes of tumour vasculature within osseous lesions non-invasively.


RESULTS
Animals treated with sorafenib tosylate or paclitaxel showed significantly reduced growth of both, the osteolytic lesions and the soft tissue tumours as well as a decreased cellularity in bone metastases compared to control rats. Effects on the tumour vasculature of these drugs included significantly reduced blood volume as well as significant changes of the vessel permeability and the mean vessel calibers. When combining sorafenib tosylate with paclitaxel for the treatment of bone metastases positive combination effects were observed, particularly on reducing vessel permeability in these lesions.


CONCLUSIONS
The application of sorafenib tosylate monotherapy or in combination with paclitaxel is effective against experimental breast cancer bone metastases resulting in anti-angiogenic, anti-tumour and anti-resorptive effects.
Merz
Maximilian
M
Department of Medical Physics in Radiology, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Komljenovic
Dorde
D
Zwick
Stefan
S
Semmler
Wolfhard
W
Bäuerle
Tobias
T
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001557:Benzenesulfonates / Q000008:administration & dosage; D001859:Bone Neoplasms / Q000188:drug therapy / Q000503:physiopathology / Q000556:secondary*; D001862:Bone Resorption / Q000188:drug therapy*; D001943:Breast Neoplasms; D005260:Female; D006801:Humans; D009536:Niacinamide / Q000031:analogs & derivatives; D017239:Paclitaxel / Q000008:administration & dosage; D010671:Phenylurea Compounds; D011725:Pyridines / Q000008:administration & dosage; D051381:Rats; D011923:Rats, Nude; D000077157:Sorafenib; D023041:Xenograft Model Antitumor Assays
D020533:Angiogenesis Inhibitors; D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib; D017239:Paclitaxel