Correlation between size and external temperature in four rat tumours after treatment with cytostatic agents.

The reduction in size of four experimental tumours (ISIS 130 and ISIS 208 immunocytomas, S 437 mammary adenocarcinoma, S 447 colon adenocarcinoma) was investigated in LOU rats under the influence of cytostatic agents belonging to different classes (5-fluorouracil, methotrexate, vinblastine, cisplatin, doxorubicin, cyclophosphamide). External tumour and rectal temperatures were measured at the same time, twice daily, during the whole experiment. With the rectal temperature of the rats kept constant, the reduction in tumour dimensions following chemotherapy correlated via a linear relationship with the duration and degree of tumour hypothermia for the three tumours S 437, ISIS 208, ISIS 130. However, for the same reduction in tumour volume following chemotherapy, the duration and degree of transient tumour hypothermia varied according to the type of tumour and cytostatic agent studied. There was not correlation between the decrease in size of S 447 and external tumour hypothermia. Even when the reduction in tumour size was statistically significant, the hypothermic tumour phase after drug administration was not sufficient to be significant, except for vinblastine. However, the temperature of this slowly growing tumour before chemotherapy was particularly low. The measurement of the degree and duration of external tumour hypothermia of tumours following chemotherapy would represent a new physiological technique for measuring the efficacy and duration of action of cytostatic agents.

Correlation between size and external temperature of the ISIS 130 tumour after treatment with cytostatic agents.

The reduction in size of the experimental ISIS 130 tumour has been investigated in LOU rats under the influence of increasing doses of cytostatic agents belonging to different classes. External temperatures of tumours as well as rectal temperatures have been measured at the same time, twice daily, during the whole experiment. The greater the decrease in the tumour size after drug administration, the larger was the decrease in external temperature of tumour. The rectal temperatures remained fairly stable, thus differences between the tumour and rectal temperatures increased. A possible correlation between the reduction of tumour size and the decrease of external temperature of tumour has been traced for every cytostatic agent, and the same linear relationship has been found to link these two parameters. The decrease in external temperature of tumour may, moreover, predict the decrease in tumour size within a term of 1-2 days. Measurement of the magnitude of the transient tumour hypothermia of ISIS 130, following chemotherapy, would represent a new method for measuring the efficiency and duration of action of cytostatic agents.

Effect of chemotherapy on tumor temperature in rats.

Two transplanted rat immunocytomas with different degrees of sensitivity to single injection of cyclophosphamide (CY) were used to assess the reliability of recording of the tumoral and rectal temperatures may be useful to evaluate the efficacy of cytostatic drugs against experimental rat tumors. With the highly sensitive tumor (ISIS 130), 25 mg/m2 of CY resulted in a pronounced tumor inhibition (Treated/Control tumors = 28%); with the less sensitive (ISIS 208), a CY dose of 320 mg/m2 was necessary to inhibit tumor growth to the same extent. The more important the decrease in tumor size was, after the administration of the drug, the larger the decrease was in tumoral temperature. Since the rectal temperature remained fairly stable, there was an increase of the difference between the tumoral and rectal temperatures. From the comparison between the results obtained for the two tumors with a wide range of CY doses, it appeared that the decrease in tumoral temperature did not correlate with the drug dose itself, but with the actual antitumor efficacy of the drug in each particular case.