In vivo potentiation of radiation response by topotecan in human rhabdomyosarcoma xenografted into nude mice.
Fiche publication
Date publication
août 2000
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BARBERI-HEYOB Muriel, Pr CHASTAGNER Pascal, Pr MERLIN Jean-Louis
Tous les auteurs :
Chastagner P, Merlin JL, Marchal C, Hoffstetter S, Barberi-Heyob M, Vassal G, Duprez A
Lien Pubmed
Résumé
The lack of new highly efficacious drugs for cancer treatment promotes the search for innovative therapeutic modalities. The authors reported the results leading to the definition of parameters needed to demonstrate a possible radiopotentiation by topotecan (TPT) on two representative human rhabdomyosarcomas (RMSs) xenografted into nude mice. Experimental studies of radiopotentiation with different doses of topotecan showed that concomitant association of topotecan and RT for 5 consecutive days provided a synergistic therapeutic effect. Response rates were statistically higher with the radiochemotherapeutic combination (P < 0.001). Efficacy enhancement factors of this combination compared with the sum of the antitumoral activity of these treatments separately administrated were 1.54 and 1.60, respectively, on both rhabdomyosarcomas. Moreover, the efficiency of the combination of radiotherapy 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 microscopy results, the analyses performed at different periods after topotecan treatment alone, radiotherapy alone, and their combination seemed to show that tumoral repopulation by malignant cells is as fast as the dose of radiotherapy and/or topotecan is low. Furthermore, lesions observed with the dose of 40 Gy were similar to those obtained with the association of topotecan at the dose of 12.5 mg/kg and radiotherapy at the dose of 20 Gy. In conclusion, all clinical and pathological results are consistent with a radiopotentiation effect of topotecan on the two xenografted human rhabdomyosarcomas and are currently leading to the design of clinical studies.
Mots clés
Adolescent, Aged, Aged, 80 and over, Animals, Antineoplastic Agents, pharmacology, Combined Modality Therapy, Dose-Response Relationship, Drug, Dose-Response Relationship, Radiation, Drug Synergism, Female, Humans, Mice, Mice, Nude, Radiation-Sensitizing Agents, pharmacology, Rhabdomyosarcoma, drug therapy, Topotecan, pharmacology, Xenograft Model Antitumor Assays
Référence
Clin. Cancer Res.. 2000 Aug;6(8):3327-33