Serious adverse effects of amifostine during radiotherapy in head and neck cancer patients

Rades, Dirk; Fehlauer, Fabian; Bajrovic, Amira; Mahlmann, Birgit; Richter, Eckart; Alberti, Winfried

doi:10.1016/j.radonc.2003.10.005

Cited by 194 publications

(121 citation statements)

References 18 publications

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“…15 Others also have reported reduced compliance because of the toxicity of amifostine. [13][14][15]31 The level of treatment discontinuation varied from 11% to 41%, depending on the dose of amifostine administered and the radiation scheme applied. One study was ended preliminary because of toxicity.…”

Section: Discussionmentioning

confidence: 99%

Radiotherapy alone, versus radiotherapy with amifostine 3 times weekly, versus radiotherapy with amifostine 5 times weekly

Jellema

Slotman

Müller

et al. 2006

Cancer

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BACKGROUND. The main objective of this study was to investigate whether nondaily intravenous administration of amifostine was as effective as daily intravenous administration with regard to the reduction of the incidence of Grade 2 or greater xerostomia in patients with head and neck cancer. METHODS. Ninety‐one patients who received bilateral irradiation for head and neck cancer were included. Thirty patients received no amifostine (AMI‐0), 31 patients received amifostine at a dose of 200 mg/m2 3 times weekly (AMI‐3), and 30 patients received amifostine at a dose of 200 mg/m2 daily (5 times weekly) (AMI‐5). Acute and late xerostomia and quality of life (QOL) were assessed at baseline, 6 weeks later, and at 6‐month intervals from 6 months to 24 months postradiotherapy. RESULTS. Grade 2 or greater late xerostomia differed significantly at 6 months (AMI‐0 74% vs. AMI‐3 67% vs. AMI‐5 52%; P = .03), but not thereafter. During follow‐up, patient‐rated xerostomia deteriorated more in AMI‐0 patients (mean difference score:, 52 for AMI‐0 compared with 25 for AMI‐3, and 29 for AMI‐5; P = .01). Nausea and emesis were reported most frequently as side effect, but Grade 2 or greater toxicity was observed in only 4 patients. However, 28% of patients discontinued amifostine before the end of radiotherapy. CONCLUSIONS. Long‐term, patient‐rated xerostomia was less for the AMI‐3 and AMI‐5 groups through 2‐year follow‐up, but no difference was noted between the AMI‐3 and AMI‐5 groups. For late xerostomia according to the Radiation Therapy Oncology Group criteria, the same effect was observed at 6 months, but not thereafter. Cancer 2006. © 2006 American Cancer Society.

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Section: Discussionmentioning

confidence: 99%

Radiotherapy alone, versus radiotherapy with amifostine 3 times weekly, versus radiotherapy with amifostine 5 times weekly

Jellema

Slotman

Müller

et al. 2006

Cancer

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“…In a study conducted by Rades et al [25], 39 patients, who received intravenous amifostine, were evaluated. Of these patients, 16 (41%) had severe toxicity, especially hypotension (11 patients), vomiting (10 patients) and allergic reaction (8 patients).…”

Section: Xerostomia Prevention Therapies Amifostinementioning

confidence: 99%

Clinical features and preventive therapies of radiation-induced xerostomia in head and neck cancer patient: a literature review

et al. 2017

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Xerostomia or dry mouth is one of the most common and disturbing adverse effects following radiotherapy for head and neck cancer (HNC). This complication strongly increases the risk for dental caries, difficulties with chewing, swallowing and sleep disorders with significant impact on patients' quality of life. Current treatment approaches of xerostomia are often difficult and bring in many cases no substantial relief for the patient. This paper discusses the clinical features and current knowledge of xerostomia prevention in order to evaluate the real possibilities of reducing the incidence and severity of this complication in HNC patients. Salivary gland cytoprotectants (amifostine), muscarinic agonist stimulation (pilocarpine and bethanechol), salivary gland-sparing radiation technique (intensity-modulated radiotherapy-IMRT), surgical relocation of the submandibular gland, intraoral stent and stem cell transplantation are promising techniques that are discussed in this study.

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“…Further, since amifostine is an organic thiophosphate that is hydrolysed in vivo by alkaline phosphatase to an active cytoprotective thiol metabolite, it is selective for non-malignant tissues that have higher levels of this enzyme. However, intervention is not perfectly discerning and causes serious side effects such as hypotension, nausea and vomiting, which greatly restricts its use 28 . Currently, another limitation with this compound is that its recommended route of administration is intravenous although newer methods such as subcutaneous and oral routes are being explored 18 .…”

Section: Agents Modulate Thementioning

confidence: 99%

Contemporary Radiation Countermeasure

Patel¹,

Gupta²,

Shareef³

et al. 2011

DSJ

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Radiation countermeasures have been investigated for decades, but the search for ideal protective agents for use prior to or after irradiation still continues. This review focuses on agents that have demonstrated as potential as in vivo countermeasure agents and may subsequently be effectively used in human beings. Such agents are categorised as radioprotectors, radiation mitigators, or therapeutic agents dependening upon their time of administration. These protective or mitigating agents are designed to reduce inadvertent damage to normal tissue caused by radiation. These interventions function via various mechanisms of action ranging from modulating signalling pathways to inhibiting cell death, cytokines, and growth factor. Many agents demonstrated promising results in murine models and are being tested in human beings. Amifostine, and curcumin have shown radioprotection, while genistein, palifermin, and halofuginone have been shown to alleviate the side effects in patients undergoing radiotherapy. Though these compounds show some promise as radiation countermeasure agents, there are several associated limitations and the search for perfect agents still continues.

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Serious adverse effects of amifostine during radiotherapy in head and neck cancer patients

Cited by 194 publications

References 18 publications

Radiotherapy alone, versus radiotherapy with amifostine 3 times weekly, versus radiotherapy with amifostine 5 times weekly

Radiotherapy alone, versus radiotherapy with amifostine 3 times weekly, versus radiotherapy with amifostine 5 times weekly

Clinical features and preventive therapies of radiation-induced xerostomia in head and neck cancer patient: a literature review

Contemporary Radiation Countermeasure

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