Effect of adriamycin combined with whole body hyperthermia on tumor and normal tissues.
Thermal enhancement of Adriamycin-mediated antitumor activity and normal tissue toxicities by whole body hyperthermia were compared using a F344 rat model. Antitumor activity was studied using a tumor growth delay assay. Acute normal tissue toxicities (i.e., leukopenia and thrombocytopenia) and late normal tissue toxicities (i.e., myocardial and kidney injury) were evaluated by functional/physiological assays and by morphological techniques. Whole body hyperthermia (120 min at 41.5 degrees C) enhanced both Adriamycin-mediated antitumor activity and toxic side effects. The thermal enhancement ratio calculated for antitumor activity was 1.6. Thermal enhancement ratios estimated for "acute" hematological changes were 1.3, whereas those estimated for "late" damage (based on morphological cardiac and renal lesions) varied between 2.4 and 4.3. Thus, while whole body hyperthermia enhances Adriamycin-mediated antitumor effect, normal tissue toxicity is also increased, and the potential therapeutic gain of the combined modality treatment is eroded.
Wondergem
J
J
University of Texas Medical School, Department of Internal Medicine, Houston.
Stephens
L C
LC
Strebel
F R
FR
Baba
H
H
Ohno
S
S
Siddik
Z H
ZH
Newman
R A
RA
Bull
J M
JM
D000818:Animals; D001806:Blood Urea Nitrogen; D001835:Body Weight; D003131:Combined Modality Therapy; D003967:Diarrhea / Q000209:etiology; D004317:Doxorubicin / Q000008:administration & dosage* / Q000633:toxicity; D005260:Female; D006331:Heart Diseases / Q000139:chemically induced / Q000473:pathology; D006410:Hematopoiesis / Q000187:drug effects; D006979:Hyperthermia, Induced; D007674:Kidney Diseases / Q000139:chemically induced / Q000473:pathology; D007958:Leukocyte Count; D009422:Nervous System Diseases / Q000139:chemically induced / Q000473:pathology; D010976:Platelet Count; D051381:Rats; D011916:Rats, Inbred F344; D012513:Sarcoma, Experimental / Q000628:therapy*
D004317:Doxorubicin