Amifostine for salivary glands in high-dose radioactive iodine treated differentiated thyroid cancer

  • Review
  • Intervention

Authors


Abstract

Background

Radioactive iodine treatment for differentiated thyroid cancer possibly results in xerostomia. Amifostine has been used to prevent the effects of irradiation to salivary glands. To date, the effects of amifostine on salivary glands in radioactive iodine treated differentiated thyroid cancer remain uncertain.

Objectives

To assess the effects of amifostine on salivary glands in high-dose radioactive iodine treated differentiated thyroid cancer.

Search methods

Studies were obtained from computerized searches of MEDLINE, EMBASE, The Cochrane Library and paper collections of conferences held in Chinese.

Selection criteria

Randomised controlled clinical trials and quasi-randomised controlled clinical trials comparing the effects of amifostine on salivary glands after radioactive iodine treatment for differentiated thyroid cancer with placebo and a duration of follow up of at least three months.

Data collection and analysis

Two authors independently assessed risk of bias and extracted data.

Main results

Two trials with 130 patients (67 and 63 patients randomised to intervention versus control) were included. Both studies had a low risk of bias. Amifostine versus placebo showed no statistically significant differences in the incidence of xerostomia (130 patients, two studies), the decrease of scintigraphically measured uptake of technetium-99m by salivary or submandibular glands at twelve months (80 patients, one study), and the reduction of blood pressure (130 patients, two studies). Two patients in one study collapsed after initiation of amifostine therapy and had to be treated by withdrawing the infusion and volume substitution. Both patients recovered without sequelae. Meta-analysis was not performed on the function of salivary glands measured by technetium-99m scintigraphy at three months after high dose radioactive iodine treatment due to the highly inconsistent findings across studies (I2 statistic 99%). None of the included trials investigated death from any cause, morbidity, health-related quality of life or costs.

Authors' conclusions

Results from two randomised controlled clinical trials suggest that the amifostine has no significant radioprotective effects on salivary glands in high-dose radioactive iodine treated differentiated thyroid cancer patients. Moreover, no health-related quality of life and other patient-oriented outcomes were evaluated in the two included trials. Randomised controlled clinical trials with low risk of bias investigating patient-oriented outcomes are needed to guide treatment choice.

摘要

背景

以Amifostine治療接受高劑量放射性碘治療的分化型甲狀腺癌(differentiated thyroid cancer)患者之唾液腺

以放射性碘治療分化型甲狀腺癌可能造成患者的口乾燥病(xerostomia)。 Amifostine已被用來預防放射治療對唾液腺的效應。Amifostine對接受放射性碘治療分化型甲狀腺癌患者的唾液腺的效果,至今仍不清楚。

目標

評估以Amifostine治療接受高劑量放射性碘治療的分化型甲狀腺癌患者之唾液腺的效果。

搜尋策略

以電腦化作業搜尋MEDLINE, EMBASE, The Cochrane Library 資料庫,以及中文研討會的論文集。

選擇標準

追蹤時間至少三個月以上,比較以Amifostine和安慰劑治療接受高劑量放射性碘治療的分化型甲狀腺癌患者之唾液腺效果的隨機對照臨床試驗(Randomised controlled clinical trials)以及準隨機對照臨床試驗(quasirandomised controlled clinical trials) 。

資料收集與分析

兩位作者各自獨立評估偏差(bias)的風險並擷取資料。

主要結論

分析兩個臨床試驗共130名病人(隨機分組產生67名實驗組及63名對照組)。兩個臨床試驗的偏差風險都低。口乾燥病的發生率(130名病人,2個臨床試驗)、12個月後閃爍造影術(scintigraphy)偵測唾液腺或下頜下腺(submandibular glands) (80名病人,1個臨床試驗)對Tc99m (technetium99m)攝取率的減少, 以及血壓的下降(130名病人,2個臨床試驗),在接受Amifostine 或安慰劑組間沒有顯著差異。其中一個研究有兩個病人在開始使用amifostine 治療後因為虛脫(collapse)而必須終止使用並補充體液。兩人後來都恢復,沒有發生後遺症。因為各研究之間高度的不一致性(I2 = 99%),所以在接受高劑量放射性碘治療三個月後以Tc99m閃爍造影術測量之唾液腺功能並未進行統合分析。這些研究均未分析任何死因、併發症、生活品質或花費。

作者結論

兩個隨機對照臨床試驗的結果顯示,amifostine對接受高劑量放射性碘治療的分化型甲狀腺癌患者之唾液腺並沒有保護的效果。而且這兩個臨床試驗也未對健康相關之生活品質或以病人為中心的其他結果進行評估。需要進行低偏差風險的隨機對照臨床試驗,並研究以病人為中心的結果來提供指引。

翻譯人

本摘要由慈濟醫院葉日弌翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

以Amifostine治療接受高劑量放射性碘治療的分化型甲狀腺癌患者之唾液腺:甲狀腺癌是內分泌系統最常見的癌,可以分成如papillary carcinoma (佔 80%) 及follicular carcinoma (佔11%)等類別。這些都統稱做「分化型甲狀腺癌」。在手術切除後以放射性碘治療對偵測轉移及消除可能殘留的顯微癌症(microscopic cancer)很重要。在放射性碘治療後,在唾液腺可能產生不良反應,導致腫痛,通常會包括腮腺。症狀可能在第一劑放射性碘隨即出現、或在治療幾個月之後才出現,並可能隨時間惡化。次發的併發症包括口乾燥病及味覺改變。一般認為在放射性碘治療時同時使用Amifostine對唾液腺並有保護的效果。這種藥是以靜脈注射投予,曾有報告說能消除放射性碘對唾液腺的破壞。我們只找到兩個隨機對照臨床試驗比較amifostine和安慰劑的療效。這兩個隨機對照臨床試驗研究130名接受高劑量放射性碘治療的分化型甲狀腺癌的病人。整體而言amifostine對接受高劑量放射性碘治療的分化型甲狀腺癌患者之唾液腺並沒有明顯的保護效果。來自同一試驗的兩個病人在開始使用amifostine治療後因為虛脫而必須終止使用並補充體液。兩人後來都恢復,沒有發生後遺症。在有更好的資料之前,使用酸糖(sour candy)或檸檬汁來為接受高劑量放射性碘治療的分化型甲狀腺癌增加口水可能更適合。必須向病人詳盡告知在接受放射性碘治療後攝取充足的水分、以酸刺激及唾液腺按摩的重要性。除此之外,早期認出口乾燥病並加以處理也會有比較好的結果。

Plain language summary

Amifostine for salivary glands in high-dose radioactive iodine treated differentiated thyroid cancer

Thyroid cancer is the most common malignancy of the endocrine system consisting of several subtypes like papillary carcinoma (accounting for 80% of cases) and follicular carcinoma (accounting for 11% of cases). These are collectively referred to as 'differentiated thyroid cancer'. Treatment with radioactive iodine after surgery (ablation of the thyroid gland or 'thyroidectomy') is important for the detection of metastatic disease and for the destruction of the remaining thyroid tissue with microscopic cancer. After radioactive iodine treatment, adverse effects may happen in the salivary glands and cause salivary gland swelling and pain, usually involving the parotid. The symptoms may develop immediately after a therapeutic dose of radioactive iodine or months later and progress in intensity with time. Secondary complications reported include dry mouth ('xerostomia') and taste alterations.

Amifostine is thought to be a radioprotector of salivary glands used in conjunction with radioiodine therapy. This medication is administered intravenously and was reported to ameliorate the damage of salivary glands caused by radioactive iodine therapy.

We found only two randomised controlled trials in which the effects of amifostine were compared with placebo. The two randomised clinical trials investigated 130 patients treated with high dose radioactive iodine for thyroid cancer. Altogether data from the two trials suggest that amifostine has no obvious protective effects on the salivary glands in these patients. Two patients in one study collapsed after initiation of amifostine therapy and had to be treated by withdrawing the infusion and volume substitution. Both patients recovered without sequelae.

Until better data become available, the use of sour candy or lemon juice to increase salivation might be more appropriate during radioactive iodine treatment for patients with differentiated thyroid cancer. Patients should be well informed of the importance of hydration, acid stimulation and glandular massage after radioactive iodine treatment. In addition, early recognition and treatment of xerostomia may improve outcomes.