Improving local tumor control by combining vascular targeting drugs, mild hyperthermia and radiation.
Improvement in local control in a foot-implanted (200 mm3) C3H mouse mammary carcinoma by combining vascular targeting drugs, mild hyperthermia and radiation was investigated. The vascular targeting drug was flavone acetic acid (FAA; 150 mg/kg) intraperitoneally injected either 3 h before local tumor water-bath heating or 1 h after local tumor irradiation. For untreated tumors, the average (+/- 1 S.E.) tumor growth time (TGT; time to reach 5 x treatment volume) was 7.1 days (+/- 0.4). This was increased to 9.2 days (+/- 0.7) by using FAA. Heating also increased TGT, the effect being temperature and time dependent, and this heat response was further increased by FAA. The radiation dose (+/- 95% confidence interval) to control 50% of tumors (TCD50) 90 days after irradiation was 52 Gy (50-55) for radiation alone. This was decreased to 42 Gy (39-45) by FAA, 47 Gy (45-50) by heating (41.5 degrees C; 60 min) 4 h after irradiation, and to 28 Gy (22-35) by combining FAA and heat. Thus, vascular targeting drugs can improve the efficacy of mild hyperthermia and radiation.
Horsman
M R
MR
Danish Cancer Society, Department of Experimental Clinical Oncology, Aarhus University Hospital, Denmark. mike@oncology.dk
Murata
R
R
Overgaard
J
J
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D005260:Female; D005419:Flavonoids / Q000627:therapeutic use*; D005528:Foot; D006979:Hyperthermia, Induced; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply / Q000532:radiotherapy / Q000628:therapy*; D051379:Mice; D008809:Mice, Inbred C3H; D008811:Mice, Inbred DBA; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D011879:Radiotherapy Dosage
D000970:Antineoplastic Agents; D005419:Flavonoids; C049328:flavone acetic acid