Combretastatins novel vascular targeting drugs for improving anti-cancer therapy. Combretastatins and conventional therapy.
Combretastatins are a new class of compounds that appear to have anti-tumour activity as a result of specifically targeting the vasculature of tumours. The aim of this study was to investigate the potential of combretastatin A-4 disodium phosphate (CA4DP) to induce vascular effects in a C3H mouse mammary carcinoma, and to see if the anti-tumour response could be improved by combining the drug with conventional anti-cancer therapies. It was found that CA4DP (250 mg/kg) significantly decreased tumour perfusion within 30 minutes after injection and maintained this decrease for several hours, although there was a return to normal by 24 hours. Similar changes were seen in the tumours bioenergetic and oxygenation status. The drug also significantly increased tumour necrosis and had a small inhibitory effect on tumour growth. It was also able to enhance the tumour response to radiation and hyperthermia, when given at the same time or 30 minutes after the radiation and hyperthermia, respectively. Giving the drug 1 hour after cisplatin injection only resulted in a tumour response that was no greater than additive. These results confirm the anti-vascular effects of CA4DP and demonstrate its potential to enhance the anti-tumour activity of conventional therapy.
Horsman
M R
MR
Danish Cancer Society, Department of Experimental Clinical Oncology, Aarhus University Hospital, Denmark.
Murata
R
R
Breidahl
T
T
Nielsen
F U
FU
Maxwell
R J
RJ
Stødkiled-Jørgensen
H
H
Overgaard
J
J
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols; D002945:Cisplatin / Q000008:administration & dosage / Q000627:therapeutic use; D003131:Combined Modality Therapy; D004359:Drug Therapy, Combination; D005260:Female; D006361:Heating; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000503:physiopathology / Q000532:radiotherapy; D051379:Mice; D008809:Mice, Inbred C3H; D013267:Stilbenes / Q000008:administration & dosage / Q000627:therapeutic use*
D000972:Antineoplastic Agents, Phytogenic; D013267:Stilbenes; C058728:fosbretabulin; D002945:Cisplatin