The general objective of this study is to establish an optimum multimodality treatment regimen using heat and chemotherapy that provides both maximum tumor ablation and minimal damage to critical dose limiting normal tissues. The response of a rat fibrosarcoma artificially metastatic to the lung will be used as a tumor model. These data will then be compared to the acute and chronic respones of those normal tissues considered dose limiting for the particular drug being tested. To determine the dose relationships of cisplatin, adriamycin, and bleomycin when given simultaneously with systemic hyperthermia on tumor response and to quantify the acute and late responses of the target normal tissues for each drug when combined with heat and with heat alone. To compare the pharmacokinetics of the chemotherapy agents at normal hyperthermic temperatures using serial tissue and serum drug analysis. To determine the effect of increasing the time interval between heat and drugs when given before and after heating on both the tumor response and the target normal tissue response. To determine if a biological response modifier, venoruton, a bioflavenoid oxyden free radical scavenging agent, preferentially spares the target normal tissue after heat and drug treatment. In addition to providing insight into the pharmacokinetics of drugs when combined with heat, and a knowledge of the effects of the combined therapies on normal tissues; the data obtained from these studies have potential importance to the management of patients using drugs combined with either local-regional or systemic hyperthermia.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA043090-03
Application #
3185008
Study Section
Radiation Study Section (RAD)
Project Start
1986-07-15
Project End
1989-06-30
Budget Start
1988-07-01
Budget End
1989-06-30
Support Year
3
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Texas Health Science Center Houston
Department
Type
Schools of Medicine
DUNS #
City
Houston
State
TX
Country
United States
Zip Code
77225
Rowe, R Wanda; Strebel, Frederick R; Proett, Jesse M et al. (2010) Fever-range whole body thermotherapy combined with oxaliplatin: a curative regimen in a pre-clinical breast cancer model. Int J Hyperthermia 26:565-76
Rowe, R Wanda; Tomoda, Masaaki; Strebel, Frederick R et al. (2004) The natural progression of microvasculature in primary tumor and lymph node metastases in a breast carcinoma model: relationship between microvessel density, vascular endothelial growth factor expression, and metastatic invasion. Cancer Biol Ther 3:408-14
Sumiyoshi, K; Strebel, F R; Rowe, R W et al. (2003) The effect of whole-body hyperthermia combined with 'metronomic' chemotherapy on rat mammary adenocarcinoma metastases. Int J Hyperthermia 19:103-18
Toyota, N; Strebel, F R; Stephens, L C et al. (1998) Therapeutic efficacy and apoptosis and necrosis kinetics of doxorubicin compared with cisplatin, combined with whole-body hyperthermia in a rat mammary adenocarcinoma. Int J Cancer 76:499-505
Toyota, N; Strebel, F R; Stephens, L C et al. (1998) Effect of altered duration of 41.5 degrees C whole body hyperthermia in combination with cis-diamminedichloroplatinum (II) on tumor and normal tissue apoptosis and tumor response in rats. Oncol Rep 5:1231-6
Toyota, N; Strebel, F R; Stephens, L C et al. (1997) Long-duration, mild whole body hyperthermia with cisplatin: tumour response and kinetics of apoptosis and necrosis in a metastatic rat mammary adenocarcinoma. Int J Hyperthermia 13:497-506
Matsuda, H; Strebel, F R; Kaneko, T et al. (1997) Long duration-mild whole body hyperthermia of up to 12 hours in rats: feasibility, and efficacy on primary tumour and axillary lymph node metastases of a mammary adenocarcinoma: implications for adjuvant therapy. Int J Hyperthermia 13:89-98
Makino, M; Lodato, R F; Stephens, L C et al. (1996) Protective effect of NG-monomethyl-L-arginine against hypotension inducted by combined tumour necrosis factor-alpha and whole body hyperthermia in rats. Int J Hyperthermia 12:617-34
Sakaguchi, Y; Stephens, L C; Makino, M et al. (1995) Apoptosis in tumors and normal tissues induced by whole body hyperthermia in rats. Cancer Res 55:5459-64
Wondergem, J; Strebel, F R; Stephens, L C et al. (1995) Chronic effect of whole-body hyperthermia combined simultaneously with cis-diamminedichloroplatinum (II) on normal tissue in rat. Int J Hyperthermia 11:37-47

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