Hypoxia-activated prodrug: an appealing preclinical concept yet lost in clinical translation
Mené sur 640 patients atteints d'un sarcome des tissus mous de stade localement avancé, métastatique ou non résécable, cet essai de phase III évalue l'efficacité, du point de vue de la survie globale, et la toxicité de l'ajout de l'évofosfamide à la doxorubicine
Hypoxia-activated prodrugs use hypoxia, an inherent feature of solid tumours that drives tumour aggressiveness and chemoresistance, for tumour targeting. Preclinical studies1 with the hypoxia-activated prodrug evofosfamide (TH-302) in mice with various human tumour xenograft models have successfully proven the concept of increased antitumour activity under reduced oxygen concentration breathing conditions. A study2 in mice with non-small cell lung cancer xenografts comparing evofosfamide with the structurally related agent ifosfamide—another prodrug that is continuously activated in the liver and is established in the treatment of soft-tissue sarcoma—suggested evofosfamide had higher antitumour activity and a more favourable safety profile than ifosfamide.
The Lancet Oncology , commentaire, 2016