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Simultaneous radio-chemotherapy is frequently used for cancer treatment. At our Center it is also complemented by hyperthermic sessions. We are interested in estimation and comparison of the modifying effects of the common chemotherapeutic agents for these physical agents acting on different cancer and ‘normal’ cells in vitro. The following cells were used in the study: human HT-29, mouse SCC-7 and hamster V-79 ‘tumor’ cells and ‘own’ skin fibroblasts and mesenchymal stromal cells as‘normal’. Cells were gamma-irradiated or treated with hyperthermia (42 or 43оС, 30 min), or irradiated and heated, in suspension in the presence of one of the chemotherapeutic compounds. The direct and combined effects of treatment were estimated by a decrease in cell clonogenicity and suppression of cell growth, measured by change in conversion of resazurin based homemade stain. As example: cycloplatam, 1µg/ml, itself decreased V-79 cell survival by 20% and increased effect of gamma-radiation on clonogenicity with dose modification factor (DMF) ≈1.4. It had only additive effect for hyperthermic treatment, which itself decreased clonogenicity by 1.14 times. Gemzar (3 µg/ml), tested on SCC-7 cells, itself decreased cell clonogenicity by 1.15 times. At this concentration it substantially increased radiation damage, decreasing cell clonogenicity by 1.68 times. The DMF of hyperthermic treatment after irradiation was only 1.07. The loss of cell clonogenicity in case of irradiation and following hyperthermia it made deeper with DMF 1.8. Paclitaxel at concentration 0,068 µМ diminished SCC-7 cells cell growth by 20%, enhancing effect of radiation with DMF =1.3 and effect of hyperthermia with DMF=1.1. Hyperthermic treatment ‘elevated’ effect of radiation with DMF=1.4.Due to its own effect on cell growth and modification of radiosensitivity, the outcome of cell irradiation in the presence of paclitaxel was 1.58 times (DMF) larger than effect of radiation alone. These data demonstrate that the combined effect of radio-thermoradiotherapy and chemotherapy of tumor cells exceeds the additive effect of these three modalities. The largest modifying effect is shown by gemzar, and this corresponds to results of other investigators. The preliminary experiments with human ‘normal’ cells indicate the smaller modifying effects of these drugs.