Hypofractionated and accelerated radiotherapy with amifostine cytoprotection (HypoARC): a new concept in radiotherapy and encouraging results in breast cancer.
Tumors with low intrinsic radiosensitivity, low alpha/beta-ratios and, eventually, hypoxic tumors unable to undergo reoxygenation (because of intrinsic reasons or radiotherapy acceleration that delivers the total dose before the onset of reoxygenation) are likely to respond better to large fractions of radiotherapy. Accelerating the course of hypofractionated radiotherapy would further target tumors with high repopulation ability. Such hypofractionated and accelerated schedules are expected to confer unacceptable toxicity. Accordingly, we investigated the cytoprotective efficacy of amifostine as a potential key to permit the safe administration of such highly toxic regimens. Hypofractionated and accelerated radiotherapy with amifostine cytoprotection (HypoARC; 3.5 to 4 Gy/d x 12 days) was tested in phase I and II trials in patients with breast cancer. Early radiation skin toxicity was significantly lower, and late toxicity from breast, lung, muscle/bone structures, and nerves compared favorably with that associated with standard radiotherapy. The reduced overall treatment time (16 days v 44 days) renders HypoARC appealing, especially to older patients or patients residing some distance from radiotherapy centers. Molecular studies showed that HypoARC significantly improves local relapse-free survival in patients with highly proliferating tumors or tumors overexpressing proteins linked to increased resistance to radiation-induced apoptosis (ie, c-erbB-2 and mutant p53). Further clinical trials have been designed to test the safety and efficacy of HypoARC in other tumor types.
Koukourakis
Michael I
MI
Department of Radiotherapy and Oncology, Democritus University of Thrace, Alexandroupolis, Greece.
D004999:Amifostine / Q000627:therapeutic use*; D017209:Apoptosis; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D015687:Cell Hypoxia; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D019610:Cytoprotection; D019583:Dose Fractionation, Radiation; D006801:Humans; D011832:Radiation Injuries / Q000517:prevention & control; D011837:Radiation-Protective Agents / Q000627:therapeutic use*
D011837:Radiation-Protective Agents; D004999:Amifostine