In vivo potentiation of radiation response by topotecan in human rhabdomyosarcoma xenografted into nude mice

The lack of new highly efficacious drugs for cancer treatment promotes the search for innovative therapeutic modalities. The authors reported the resu lts leading to the definition of parameters needed to demonstrate a possibl e radiopotentiation by topotecan (TPT) on two representative human rhabdomy osarcomas (RMSs) xenografted into nude mice. Experimental studies of radiop otentiation with different doses of topotecan showed that concomitant assoc iation of topotecan and RT for 5 consecutive days provided a synergistic th erapeutic effect. Response rates were statistically higher with the radioch emotherapeutic combination (P < 0.001), Efficacy enhancement factors of thi s combination compared with the sum of the antitumoral activity of these tr eatments separately administrated were 1.54 and 1.60, respectively, on both rhabdomyosarcomas, Moreover, the efficiency of the combination of radiothe rapy at the dose of 20 Gy with topotecan (12.5 mg/kg) was not statistically different from that of radiotherapy at the dose of 40 Gy, According to mic roscopy results, the analyses performed at different periods after topoteca n treatment alone, radiotherapy alone, and their combination seemed to show that tumoral repopulation by malignant cells is as fast as the dose of rad iotherapy and/or topotecan is low. Furthermore, lesions observed with the d ose of 40 Gy were similar to those obtained with the association of topotec an at the dose of 12.5 mg/kg and radiotherapy at the dose of 20 Gy, In conc lusion, all clinical and pathological results are consistent with a radiopo tentiation effect of topotecan on the two xenografted human rhabdomyosarcom as and are currently leading to the design of clinical studies.