PURPOSE: To test the importance of the sequence of cisplatin and irradiation, either conventional or accelerated fractionated. METHODS AND MATERIALS: 30 fractions of 2 Gy were given in 6 or 3 weeks preceded or followed by (time interval between cisplatin and radiotherapy: 3 days) a single IP dose of 5 mg/kg cisplatin in the rhabdomyosarcoma R1H of the rat. Survival curves were generated, and comparisons were made by the log-rank test. RESULTS: After 60 Gy in 6 weeks, no local tumor controls were observed. If cisplatin was injected 3 days before start of 60 Gy/6 weeks, 11 +/- 10% (mean +/- SE) of the tumors were controlled. Cisplatin after radiotherapy resulted in 50 +/- 14% local controls. The difference was significant (p = 0.01) for cisplatin after radiotherapy in comparison to radiotherapy alone where no local controls were observed. After accelerated fractionation, 57 +/- 19% of the animals were cured with or without cisplatin before radiotherapy. If the drug was injected after end of 60 Gy/3 weeks, 86 +/- 13% survived recurrence free. The difference to accelerated radiotherapy alone was not significant. Accelerated radiotherapy produced significantly higher control rates than conventional radiotherapy (p <0.001). CONCLUSIONS: Accelerated radiotherapy resulted in higher local tumor control rates as compared to conventional fractionated irradiation. Cisplatin combined with radiotherapy showed significantly better results if given after but not before irradiation, either conventional or accelerated fractionated.
