THERMAL ENHANCEMENT OF THE EFFECT OF IFOSFAMIDE AGAINST A SPONTANEOUSMURINE FIBROSARCOMA, FSA-II

The effect of hyperthermia on the cytotoxicity of oroethyl)-2-[(2-chlo roethyl)amino]-tetrahydro-2H-1 ,3,2-oxazaphosphorine-2-oxide, ifosfami de (IFO) was investigated in vivo. Tumours were early generation isotr ansplants of a spontaneous C3Hf/Sed mouse fibrosarcoma, FSa-II. The tu mour cell suspensions containing similar to 2 x 10(5) cells were trans planted into the dorsal site of the C3Hf/Sed mouse foot. Hyperthermia was given by immersing the tumour-bearing foot into a constant tempera ture water bath set at 41.5 degrees C for 0-90 min when tumours reache d 34mm(3). IFO was administered ip immediately before hyperthermia. Tu mour response was studied by the tumour growth (TG) time assay; namely , the TG time or the time for one-half of the treated tumours to reach 700mm(3) from the initial treatment day was determined and the dose-r esponse curve was fittted between the TG time and IFO dose. The anti-t umour effect of IFO was enhanced at this elevated temperature. The the rmal enhancement ratio (TER) or the ratio of the slope of dose-respons e curve at 41.5 degrees C to that of dose-response curve without hyper thermia was relatively small for a short treatment time of 30 min. Thi s TER was smaller for IFO than the TERs for cyclophosphamide (CY) and BCNU which had been studied in our laboratory. However, the TER for IF O increased greatly with a prolongation of treatment time from 30 to 9 0 min, and exceeded the TER for CY. The TERs were 1.5, 2.6 and 3.6 for heating time of 30, 60, and 90 min, respectively, indicating that a l ong treatment time such as 90 min at moderately elevated temperatures could result in a substantial enhancement of the antitumour effect of IFO.