The influence of combretastatin A-4 and vinblastine on interstitial fluid pressure in BT4An rat gliomas.
The influence of combretastatin A-4 disodium phosphate (CA-4, 50mg/kg intraperitoneally (i.p.)) and vinblastine (2mg/kg i.p.) on interstitial fluid pressure (IFP) was assessed in BT4An rat gliomas implanted subcutaneously in the neck. Furthermore the growth inhibitory effect of vinblastine and the distribution of fluorescence-conjugated vinblastine (BODIPY-vinblastine) were investigated. Tumors at different volumes were compared. Whereas CA-4 had no major influence on IFP, independent of tumor size, vinblastine increased the IFP in neoplasms above 8 cm(3) (P=0.03). Vinblastine yielded a significant tumor response only in tumors below 2.1 cm(3) (P=0.03). The distribution of BODIPY-vinblastine was heterogeneous and comparable despite tumor volume differences. We conclude that the influence of vinblastine on IFP is more pronounced than that of CA-4 in BT4An neck tumors, and that vinblastine may reduce subsequent drug delivery to solid tumors by increasing the IFP.
Eikesdal
Hans Petter
HP
Department of Oncology, University of Bergen, Haukeland University Hospital, 5021 Bergen, Norway. hans_eikesdal@hotmail.com
Landuyt
Willy
W
Dahl
Olav
O
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D016503:Drug Delivery Systems; D005110:Extracellular Space / Q000187:drug effects* / Q000502:physiology; D005260:Female; D005910:Glioma / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D009368:Neoplasm Transplantation; D011312:Pressure; D051381:Rats; D013267:Stilbenes / Q000494:pharmacology* / Q000627:therapeutic use; D014747:Vinblastine / Q000494:pharmacology* / Q000627:therapeutic use
D000972:Antineoplastic Agents, Phytogenic; D013267:Stilbenes; D014747:Vinblastine; C058728:fosbretabulin