Phase II multicenter randomized study of amifostine for prevention of acute radiation rectal toxicity: Topical intrarectal versus subcutaneous application

Kouloulias, Vassilis; Kouvaris, John; Pissakas, George; Mallas, E.; Antypas, Christos; Kokakis, John; Matsopoulos, George K.; Michopoulos, Spyros; Mystakidou, Kyriaki; Vlahos, Lambros

doi:10.1016/j.ijrobp.2004.10.043

Cited by 45 publications

(30 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, these studies demonstrate that various routes of administration of amifostine (i.v., s.c., and intrarectal) are effective at reducing radiation-and chemoradiation-induced gastrointestinal toxicities in patients with pelvic malignancies. One study, conducted in 53 patients with prostate or gynecologic cancer, directly compared intrarectal amifostine administration with s.c. administration and found that intrarectal administration was more effective at reducing radiotherapy-induced rectal toxicities, whereas s.c. administration was more effective at reducing radiotherapy-induced urinary toxicities (Table 2) [43]. These results suggest that optimal cytoprotection may be achieved by combining routes of amifostine administration during treatment.…”

Section: Lower Gastrointestinal Mucositismentioning

confidence: 80%

Amifostine: The First Selective-Target and Broad-Spectrum Radioprotector

2007

Self Cite

View full text Add to dashboard Cite

LEARNING OBJECTIVESAfter completing this course, the reader will be able to:1. Select appropriate multidisciplinary treatment regimens and cytoprotection for clinical trials for patients with head and neck cancer.2. Identify radiation toxicity for the head and neck, lung, and pelvic irradiated areas.3. Describe the cytoprotective effect of amifostine against radiation toxicity.Access and take the CME test online and receive 1 AMA PRA Category 1 Credit ™ at CME.TheOncologist.com CME CME ABSTRACTAfter several decades of preclinical and clinical research, the first approved radioprotective drug, amifostine, is being used in clinical practice. Amifostine has been shown to specifically protect normal tissues from damage caused by radiation and chemotherapy. An inactive prodrug, amifostine is converted to an active thiol by dephosphorylation by alkaline phosphatase in the normal endothelium. The hypovascularity and acidity of the tumor environment and the differential expression of alkaline phosphatase in normal and neoplastic tissues contribute to its cytoprotective selectivity. The cytoprotective mechanism of amifostine is complicated, involving free-radical scavenging, DNA protection and repair acceleration, and induction of cellular hypoxia. The U.S. Food and Drug Administration has approved the i.v. use of amifostine to reduce the cumulative renal toxicity associated with repeated administration of cisplatin in patients with advanced ovarian cancer and to reduce the incidence of moderate to severe xerostomia in patients undergoing postoperative radiation treatment for head and neck cancer, where the radiation port includes a substantial portion of the parotid glands. Nonetheless, amifostine has potential applications in many other oncologic settings. Novel schedules and routes of administration are under investigation and may further simplify the use of amifostine, reduce any undesired effects, and considerably broaden its applications. This review summarizes the clinical experience with amifostine and provides insight into future clinical directions. The Oncologist 2007;12:738 -747

show abstract

Section: Lower Gastrointestinal Mucositismentioning

confidence: 80%

Amifostine: The First Selective-Target and Broad-Spectrum Radioprotector

2007

Self Cite

View full text Add to dashboard Cite

show abstract

“…Furthermore, these studies demonstrate that various routes of administration of amifostine (i.v., s.c., and intrarectal) are effective at reducing radiation-and chemoradiation-induced gastrointestinal toxicities in patients with pelvic malignancies. One study, conducted in 53 patients with prostate or gynecologic cancer, directly compared intrarectal amifostine administration with s.c. administration and found that intrarectal administration was more effective at reducing radiotherapy-induced rectal toxicities, whereas s.c. administration was more effective at reducing radiotherapy-induced urinary toxicities (Table 3) (Kouloulias et al, 2005). These results suggest that optimal cytoprotection may be achieved by combining routes of amifostine administration during treatment.…”

Section: Lower Gastrointestinal Mucositismentioning

confidence: 80%

The Cytoprotective Effect of Amifostine Against Radiation Induced Toxicity

Kouloulias¹,

Kouvaris²

2012

Modern Practices in Radiation Therapy

View full text Add to dashboard Cite

“…This differential uptake of free thiol is a result of differences in the microenvironment at the tissue level, such as lower capillary alkaline phosphatase activity, lower pH, and poorer vascularity in tumor tissues than normal tissues, resulting in the slow entry of free thiol into tumor masses. Several studies have been conducted on the cytoprotective effect of amifostine against radiation-induced toxicity in pelvic irradiated areas (9,10,22,23). Pre-treatment amifostine administered either by intracolonic or intraperitoneal instillation demonstrated a radioprotective effect in the murine colon and the rectum.…”

Section: Discussionmentioning

confidence: 99%

“…This substance selectively protects normal cells from radiation toxicity by scavenging free radicals, by donating hydrogen ions to free radicals, and by depleting oxygen, thus diminishing the indirect oxidative effect of ionizing radiation on cellular components, especially on DNA. Previous studies have showed substantial radioprotective effects of amifostine on the rectal mucosa by systemic administration (9,10). Accordingly, the topical administration of amifostine on the rectal mucosa may be a possible strategy to permit safe dose escalation of the drug and prevention of the side effects (such as hypotension, nausea, vomiting, allergic and skin reactions, etc.…”

Section: Introductionmentioning

confidence: 99%