Combined modality treatment of the rhabdomyosarcoma R1H of the rat: influence of sequence of cisplatin and fractionated irradiation.

Abstract

The effect of irradiation with 30 fractions of 2 Gy in 6 weeks combined with a single dose of 5mg/kg cisplatin was studied in the rhabdomyosarcoma R1H of the rat and tumor response and normal tissue toxicity were assessed for various combinations of radiotherapy and chemotherapy. Cisplatin was given 3 days before, during (after the 5th and after the 10th fraction), or 3 and 17 days after radiotherapy. Five of the 12 tumors treated with cisplatin injected 3 days after radiotherapy were locally controlled (42%; 95% confidence intervals: 14-70%) as compared to 0/10 for radiotherapy alone (0%; 0-21%; p < 0.02). A similar trend was found for cisplatin injected 17 days after irradiation (2/6 local controls; 33%; 0-71%). With cisplatin given 3 days before radiotherapy 1/13 local controls were observed (8%; 0-22%; p < 0.05 when tested vs. cisplatin 3 days after radiotherapy). Tumor cure was dependent upon tumor size at time of cisplatin administration with 7/9 small tumors (< 2 mm3) cured versus only 2/35 cures of larger tumors (> 2 mm3). By contrast, net growth delay and skin damage were the same for combined modality treatment and for irradiation alone. General toxicity as assessed by body weight change was significantly higher for animals treated with cisplatin before or after radiotherapy, whereas cisplatin during radiotherapy showed equal effects as compared to radiotherapy alone. Although for the rhabdomyosarcoma R1H of the rat the combined modality treatment was shown to be more effective than radiotherapy alone when cisplatin was applied after radiotherapy, general toxicity was also higher for this mode of treatment.