Protection of Normal Tissue against Late Radiation Injury by WR-2721

Utley, Joe R.; Quinn, Carole A.; White, Fred N.; Seaver, N. A.; Bloor, C. M.

doi:10.2307/3575574

Cited by 30 publications

(3 citation statements)

References 21 publications

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“…This different uptake is due to higher pH and alkaline phosphatase activity in normal tissue compared to tumor tissue that causes the conversion of amifostine into active, protective thiol, WR-1065 [36], which in turn acts as a scavenger of oxygen free radicals inside the cell [1]. Interestingly, the highest tissue levels of amifostine and its metabolites are found in salivary glands [39][40][41][57][58][59], but accumulation in thyroid tissue was found to be negligible [39,63]. Submandibular gland tissue is postulated to be relatively resistant to ionizing irradiation in the same dosage range [1,19,47].…”

Section: Discussionmentioning

confidence: 99%

Amifostine is a Potent Radioprotector of Salivary Glands in Radioiodine Therapy

et al. 2005

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Section: Discussionmentioning

confidence: 99%

Amifostine is a Potent Radioprotector of Salivary Glands in Radioiodine Therapy

et al. 2005

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“…23 Thus, amifostine is an ideal radioprotector in thyroid cancer because RAI damages normal tissues within the first several hours upon administration. Biodistribution studies have found that the highest concentration of amifostine and its metabolites are found in salivary glands [24][25][26][27] but accumulation in thyroid tissue was negligible. 15,28 WR-1065 exerts its cytoprotective effect by acting as a free-radical scavenger and prevents tissue damage from oxygen freeradicals produced by radiation.…”

Section: Discussionmentioning

confidence: 99%

Prospective Single-Arm Study of Radioprotection by Amifostine in High Dose Radioactive Iodine Therapy for Thyroid Cancer

Sandhu¹,

Ioffe²,

Karakla³

et al. 2012

Journal of Postgraduate Medicine, Education and Research

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Purpose Xerostomia, sialoadenitis, taste dysfunction and nausea are well known toxicities following high dose radioactive iodine (RAI) treatment for well-differentiated thyroid cancer. This prospective study sought to determine the incidence rates for RAI adverse effects and to determine, whether the radioprotector, amifostine could decrease the duration of the adverse effects in single treatment patients. Materials and methods Patients with differentiated thyroid cancer received 150 mCi RAI after total thyroidectomy. All patients were pretreated with 1 mg granisetron and 4 mg dexamethasone. Patients in the amifostine arm (n = 27) were prospectively enrolled and received 500 mg amifostine subcutaneously. Adverse effects were scored based on the CTCAE at 1 month, 6 months, and yearly intervals using a physician administered questionnaire. The results were compared with a retrospective no amifostine cohort (n = 22) for whom data was collected with the identical questionnaire. Results The overall incidence of xerostomia, sialadenitis, taste dysfunction and nausea in the treatment group was 26, 22, 52 and 26% respectively. Only grades 1 and 2 adverse effects were observed. The mean duration (days) of xerostomia (control vs treatment)—37.3 vs 21.9 (F test, p = 0.016), taste dysfunction—45.5 vs 23.5 (F test, p = 0.001), sialadenitis— 16.8 vs 7.5 and nausea—18.7 vs 5.1. Conclusion In patients treated once with high dose RAI, who develop xerostomia, sialoadenitis, taste dysfunction, and/or nausea, the duration of symptoms appears to be reduced by pretreatment with 500 mg of subcutaneous amifostine without significant treatment related adverse effects. How to cite this article Sandhu A, Ioffe V, Karakla D, Wadsworth JT, Mendoza A, Rao N, Dignan K, Mason E, Goffman TE. Prospective Single-Arm Study of Radioprotection by Amifostine in High Dose Radioactive Iodine Therapy for Thyroid Cancer. J Postgrad Med Edu Res 2012;46(2):90-94.

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“…For this reason, Phase I and II clinical trials with WR-2721 are already under way in the United States and in Japan (Kligermanetal., 1980;Tanaka & Sugahara, 1980). Various authors have reported large protection factors (PF) * with this drug in a variety of normal tissues, and very little radioprotection has been observed in most experimental tumour systems (Yuhas & Storer, 1969a;Yuhas, 1973;Phillips et al, 1973;Utley et al, 1974;Utley et al, 1978;Sodicoff et al, 1979;Kinnamonetal, 1980;Yuhas et al, 1980a;Utley et al, 1981). If the radioprotective effect of WR-2721 on normal tissues can be reliably predicted, and if it does not protect tumours, particularly during fractionated radiotherapy, then this compound would be of great value in clinical radiation therapy.…”

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confidence: 96%

Radioprotection of mouse skin by WR-2721 in single and fractionated treatments

Stewart¹,

Rojas²

1982

BJR

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The radioprotective action of WR-2721 on mouse skin has been studied using single doses, two and five fractions. Significant radioprotection was observed with 200-500 mg/kg, in animals breathing air or oxygen at the time of irradiation. The degree of radioprotection increased with increasing dose, and was significantly greater in air than in oxygen, especially at low drug doses. Cumulative drug toxicity limited the fractionated treatments to lower drug doses, but the protection observed was similar to that seen with single doses at the same drug levels. The protection factors observed are lower than many published values for skin, and we conclude that a single protection factor cannot yet be stated for any dose of WR-2721. Local tissue oxygenation may account for some of the discrepancies in different studies.

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Protection of Normal Tissue against Late Radiation Injury by WR-2721

Cited by 30 publications

References 21 publications

Amifostine is a Potent Radioprotector of Salivary Glands in Radioiodine Therapy

Amifostine is a Potent Radioprotector of Salivary Glands in Radioiodine Therapy

Prospective Single-Arm Study of Radioprotection by Amifostine in High Dose Radioactive Iodine Therapy for Thyroid Cancer

Radioprotection of mouse skin by WR-2721 in single and fractionated treatments

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