Salivary gland protection by amifostine in high-dose radioiodine treatment: results of a double-blind placebo-controlled study.

Bohuslavizki, K. H.; Klutmann, Susanne; Brenner, Winfried; Mester, János; Henze, Eberhard; Clausen, M.

doi:10.1200/jco.1998.16.11.3542

Cited by 90 publications

(62 citation statements)

References 23 publications

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“…These trials have shown that amifostine protects against the cytotoxic effects of cisplatin, cyclophosphamide, and radiation therapy. In addition, amifostine protects against xerostomia in patients with head and neck cancer treated with radiation therapy and in patients with thyroid cancer treated with high-dose radio-iodine (Bohuslavizki et al, 1998;Buntzel et al, 1998). Recent observations also indicate that amifostine improves cytopenia in patients with myelodysplastic syndromes (List et al, , 1998.…”

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confidence: 99%

p53 protein regulates the effects of amifostine on apoptosis, cell cycle progression, and cytoprotection

et al. 2003

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To determine the role of p53 protein on the cellular effects of amifostine, we used molecularly engineered HCT116 colon cancer cells in which the p53 gene was inactivated by targeted homologous recombination or p53 protein was degraded by high-level expression of papillomavirus E6 protein. Amifostine induced a G1 arrest and protected against paclitaxel toxicity in p53-proficient but not in p53-deficient cells. In the absence of p53 protein, amifostine enhanced the cytotoxicity of paclitaxel. In addition, treatment of HCT116 cells with amifostine alone resulted in apoptotic cell death. Compared with p53-deficient cells, p53-proficient cells exhibited low-level resistance to amifostine-induced apoptosis. Amifostine induced the expression of p53 protein in p53-proficient cells and the expression of p21 protein in both p53-proficient and -deficient cells. These findings indicate that amifostine-induced G1 arrest and cytoprotection are mediated via a pathway that is dependent on p53 protein and that amifostine-induced expression of p21 protein is not sufficient to sustain a G1 arrest or to mediate cytoprotection. In addition, these findings identify p53 protein as a mechanism of resistance to amifostine-induced apoptosis.

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confidence: 99%

p53 protein regulates the effects of amifostine on apoptosis, cell cycle progression, and cytoprotection

et al. 2003

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“…Reducing the salivary gland dose will be crucial to reduce the rates of these events. The value of increasing salivation by sour juice and lemon candy remains elusive (8,10), whereas amifostine reduces salivary gland impairment in high-dose radioiodine treatment (10). Our results on the long-term consequences highlight the need to reduce initial salivary gland impairment.…”

Section: Discussionmentioning

confidence: 62%

“…Salivary glands are highly radiosensitive (5) and, accordingly, sialadenitis and xerostomia are the most frequent adverse events of high-dose radioiodine therapy (6). The incidence of sialadenitis after high-dose radioiodine therapy is about 30% (7)(8)(9), and consequent reduced salivary gland function (10) and altered saliva composition (11) develop in all patients. Clinically relevant xerostomia with dry mouth, taste loss, and swallowing difficulties arises in 11%-44% (7)(8)(9).…”

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confidence: 99%

The Dental Safety Profile of High-Dose Radioiodine Therapy for Thyroid Cancer: Long-Term Results of a Longitudinal Cohort Study

Walter¹,

Turtschi²,

Schindler³

et al. 2007

Journal of Nuclear Medicine

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The long-term dental safety profile of high-dose radioiodine therapy remained elusive despite more than 6 decades of clinical use. Methods: In a cohort study, we investigated the incidence of sialadenitis, xerostomia, caries, and tooth extractions after high-dose radioiodine therapy for differentiated thyroid cancer and explored risk factors by multiple regression models. Results: One hundred seventy-six participants were recruited (median follow-up, 6.6 y; range, 1.1-32.6 y; patient-years: 8,472 before and 1,421 after radioiodine therapy). Scintigraphic salivary gland uptake during radioiodine treatment predicted development of sialadenitis (odds ratio: 1.31 [1.05-1.63], P 5 0.015) and xerostomia (odds ratio: 1.58 [1.16-2.16], P 5 0.004). The caries risk increased by postradioiodine xerostomia (% increase: 98.8 [26.5-212], P 5 0.003). The long-term risk for postradioiodine tooth extractions increased with increasing cumulative radioiodine activities (% increase [per gigabequerel]: 8.14 [1.07, 15.7], P 5 0.02). Conclusion: High-dose radioiodine treatment can impair the long-term dental health, depending on the cumulative radioiodine activity and individual salivary gland radioiodine uptake.

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“…[20][21][22] This cytoprotection has been shown to be mostly effective on normal cells without any interaction with the tumour cells and the anticancer treatment. 16,[23][24][25][26] The present study aimed to evaluate the effect of amifostine on the acute and late side effects of RT, and its tolerability in patients receiving RT for the treatment of head and neck cancer.…”

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confidence: 99%

“…Preclinical studies reported that while amifostine (Ethyol ® ) decreased the level of damage to the parotid gland due to its cytoprotective property, it also protected normal tissues other than the parotid gland against the side effects of RT and chemotherapy (CT). [11][12][13][14][15][16][17][18] Amifostine is a phosphorylated aminothiol (WR2721) prodrug that preferentially accumulates in the salivary gland where it is metabolized to its active form by alkaline phosphatase, WR1065. 19 This active metabolite acts as a free radical scavenger and is considered the effective cytoprotector against side effects of both CT and RT.…”

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confidence: 99%

The Effect of Amifostine on Acute and Late Radiation Side Effects in Head and Neck Cancer Patients

Demiroz¹,

Özkan²,

Cebelli³

et al. 2012

Turkiye Klinikleri J Med Sci

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A AB BS ST TR RA AC CT T O Ob bj je ec ct ti iv ve e: : We aimed to investigate the effect of amifostine on acute and late side effects, and its tolerability in head and neck cancer patients treated with radiotherapy (RT). M Ma at te er ri ia al l a an nd d M Me et th ho od ds s: : The study included 87 patients with primary head and neck cancers and cervical lymph node metastases from unknown primary cancers treated with RT alone or combined with chemotherapy (CT). Forty-one patients (47%) received amifostine combined with RT (ART group) and 46 patients (52%) received RT without amifostine (RT group). The patients were evaluated every week during the treatment and at month 1 and 2 after the completion of RT for acute side effects and month 3, 6, 9, 12, and 24 after the treatment for late side effects according to SOMA/LENT scale. Amifostine was administered prior to RT, along with anti-emetic prophylaxis. The two groups were compared with the Student's t and MannWhitney U and Chi-square tests. R Re es su ul lt ts s: : The ART group had significantly less toxicity (grade 1 mucositis, grade 2 fibrosis) than patients in the RT group (p=0.001, p=0.03, respectively). At week 3 of RT grade 2 mucositis developed in two patients (5%) in the ART group and 10 patients (22%) in the RT group (p=0.02). The protective effect of amifostine on skin reactions developed at week 4 of RT (p=0.05). Grade 3 xerostomia at 9, 12, and 15 months of follow-up (p=0.02, p=0.02, and p=0.02, respectively), grade 2 xerostomia at 18 and 24 months (p=0.02 and p=0.01, respectively) and fibrosis at 15, 18 and 24 months (p=0.05, p=0.02 and p=0.02, respectively) decreased markedly in the ART group compared with the RT group. Emesis was the most common adverse effect of amifostine. C Co on nc cl lu us si io on n: : Daily administration of amifostine during RT was effective in avoiding late grade 2-3 xerostomia, as well as grade 2 fibrosis. K Ke ey y W Wo or rd ds s: : Radiotherapy; head and neck cancer; amifostine; xerostomia Ö ÖZ ZE ET T A Am ma aç ç: : Amifostinin radyoterapi (RT) ile tedavi edilmiş baş ve boyun kanseri hastalarında akut ve geç yan etkiler üzerindeki etkisini ve tolerabilitesini araştırmayı amaçladık. G Ge er re eç ç v ve e Y Yö ön nt te em ml le er r: : Çalışmaya, tek başına RT veya RT ve eş zamanlı kemoterapi (KT) ile tedavi edilmiş primer baş ve boyun kanseri olan ve primeri bilinmeyen bir kanserden servikal lenf düğümlerine metastaz yapmış 87 hasta dâhil edildi. Kırk bir hastaya (47%) RT ile birlikte amifostin (ART grup) ve 46 hastaya (52%) amifostin olmaksızın RT (RT grubu) verildi. Olgular, tedavi sırasında akut yan etkiler açısından her hafta ve RT bittikten sonra 1. ve 2. ayda, geç yan etkiler açısından ise tedavi bittikten sonra 3., 6., 9., 12., ve 24. aylarda SOMA/LENT skalasına göre değerlendirildiler. Amifostin RT'den önce antiemetik profilaksi ile beraber uygulandı. İki grubun, komplikasyonlar üzerindeki etki açısından karşılaştırılmasında Student-t ve Mann Whitney-u testleri kullanıldı. B Bu ul lg gu ul la ar r: : AR...

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Salivary gland protection by amifostine in high-dose radioiodine treatment: results of a double-blind placebo-controlled study.

Abstract: Parenchymal damage in salivary glands caused by HD-RIT can significantly be reduced by amifostine, which may improve the quality of life of patients with differentiated thyroid cancer.

Cited by 90 publications

References 23 publications

p53 protein regulates the effects of amifostine on apoptosis, cell cycle progression, and cytoprotection

p53 protein regulates the effects of amifostine on apoptosis, cell cycle progression, and cytoprotection

The Dental Safety Profile of High-Dose Radioiodine Therapy for Thyroid Cancer: Long-Term Results of a Longitudinal Cohort Study

The Effect of Amifostine on Acute and Late Radiation Side Effects in Head and Neck Cancer Patients

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