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Effect of Adriamycin Combined with Whole Body Hyperthermia on Tumor and Normal Tissues¹

University of Texas Medical School at Houston, Department of Internal Medicine [J. W., F. R. S., H. B., S. O., J. M. C. B.], and M. D. Anderson Cancer Center, Departments of Veterinary Medicine [L. C. S.] and Medical Oncology [Z. H. S., R. A. N.], Houston, Texas 77030

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°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.

¹ Supported by National Cancer Institute Grant RO1-CA-43090.

² Present address: University Hospital Leiden, Department of Clinical Oncology, Rijnsburgerweg 10, 2333 AA Leiden, The Netherlands.

³ on leave from Department of Surgery II, Faculty of Medicine, Kyushu University, Fukuoka 812, Japan.

⁴ To whom requests for reprints should be addressed.

Received 10/15/90. Accepted 4/22/91.