Riley Philip, Glenny Anne-Marie, Hua Fang, Worthington Helen V
Cochrane Oral Health, Division of Dentistry, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, JR Moore Building, Oxford Road, Manchester, UK, M13 9PL.
Cochrane Database Syst Rev. 2017 Jul 31;7(7):CD012744. doi: 10.1002/14651858.CD012744.
Salivary gland dysfunction is an 'umbrella' term for the presence of either xerostomia (subjective sensation of dryness), or salivary gland hypofunction (reduction in saliva production). It is a predictable side effect of radiotherapy to the head and neck region, and is associated with a significant impairment of quality of life. A wide range of pharmacological interventions, with varying mechanisms of action, have been used for the prevention of radiation-induced salivary gland dysfunction.
To assess the effects of pharmacological interventions for the prevention of radiation-induced salivary gland dysfunction.
Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 14 September 2016); the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 8) in the Cochrane Library (searched 14 September 2016); MEDLINE Ovid (1946 to 14 September 2016); Embase Ovid (1980 to 14 September 2016); CINAHL EBSCO (Cumulative Index to Nursing and Allied Health Literature; 1937 to 14 September 2016); LILACS BIREME Virtual Health Library (Latin American and Caribbean Health Science Information database; 1982 to 14 September 2016); Zetoc Conference Proceedings (1993 to 14 September 2016); and OpenGrey (1997 to 14 September 2016). We searched the US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases.
We included randomised controlled trials, irrespective of their language of publication or publication status. Trials included participants of all ages, ethnic origin and gender, scheduled to receive radiotherapy on its own or in addition to chemotherapy to the head and neck region. Participants could be outpatients or inpatients. We included trials comparing any pharmacological agent regimen, prescribed prophylactically for salivary gland dysfunction prior to or during radiotherapy, with placebo, no intervention or an alternative pharmacological intervention. Comparisons of radiation techniques were excluded.
We used standard methodological procedures expected by Cochrane.
We included 39 studies that randomised 3520 participants; the number of participants analysed varied by outcome and time point. The studies were ordered into 14 separate comparisons with meta-analysis only being possible in three of those.We found low-quality evidence to show that amifostine, when compared to a placebo or no treatment control, might reduce the risk of moderate to severe xerostomia (grade 2 or higher on a 0 to 4 scale) at the end of radiotherapy (risk ratio (RR) 0.35, 95% confidence interval (CI) 0.19 to 0.67; P = 0.001, 3 studies, 119 participants), and up to three months after radiotherapy (RR 0.66, 95% CI 0.48 to 0.92; P = 0.01, 5 studies, 687 participants), but there is insufficient evidence that the effect is sustained up to 12 months after radiotherapy (RR 0.70, 95% CI 0.40 to 1.23; P = 0.21, 7 studies, 682 participants). We found very low-quality evidence that amifostine increased unstimulated salivary flow rate up to 12 months after radiotherapy, both in terms of mg of saliva per 5 minutes (mean difference (MD) 0.32, 95% CI 0.09 to 0.55; P = 0.006, 1 study, 27 participants), and incidence of producing greater than 0.1 g of saliva over 5 minutes (RR 1.45, 95% CI 1.13 to 1.86; P = 0.004, 1 study, 175 participants). However, there was insufficient evidence to show a difference when looking at stimulated salivary flow rates. There was insufficient (very low-quality) evidence to show that amifostine compromised the effects of cancer treatment when looking at survival measures. There was some very low-quality evidence of a small benefit for amifostine in terms of quality of life (10-point scale) at 12 months after radiotherapy (MD 0.70, 95% CI 0.20 to 1.20; P = 0.006, 1 study, 180 participants), but insufficient evidence at the end of and up to three months postradiotherapy. A further study showed no evidence of a difference at 6, 12, 18 and 24 months postradiotherapy. There was low-quality evidence that amifostine is associated with increases in: vomiting (RR 4.90, 95% CI 2.87 to 8.38; P < 0.00001, 5 studies, 601 participants); hypotension (RR 9.20, 95% CI 2.84 to 29.83; P = 0.0002, 3 studies, 376 participants); nausea (RR 2.60, 95% CI 1.81 to 3.74; P < 0.00001, 4 studies, 556 participants); and allergic response (RR 7.51, 95% CI 1.40 to 40.39; P = 0.02, 3 studies, 524 participants).We found insufficient evidence (that was of very low quality) to determine whether or not pilocarpine performed better or worse than a placebo or no treatment control for the outcomes: xerostomia, salivary flow rate, survival, and quality of life. There was some low-quality evidence that pilocarpine was associated with an increase in sweating (RR 2.98, 95% CI 1.43 to 6.22; P = 0.004, 5 studies, 389 participants).We found insufficient evidence to determine whether or not palifermin performed better or worse than placebo for: xerostomia (low quality); survival (moderate quality); and any adverse effects.There was also insufficient evidence to determine the effects of the following interventions: biperiden plus pilocarpine, Chinese medicines, bethanechol, artificial saliva, selenium, antiseptic mouthrinse, antimicrobial lozenge, polaprezinc, azulene rinse, and Venalot Depot (coumarin plus troxerutin).
AUTHORS' CONCLUSIONS: There is some low-quality evidence to suggest that amifostine prevents the feeling of dry mouth in people receiving radiotherapy to the head and neck (with or without chemotherapy) in the short- (end of radiotherapy) to medium-term (three months postradiotherapy). However, it is less clear whether or not this effect is sustained to 12 months postradiotherapy. The benefits of amifostine should be weighed against its high cost and side effects. There was insufficient evidence to show that any other intervention is beneficial.
唾液腺功能障碍是一个“统称”，涵盖口干（主观的干燥感觉）或唾液腺功能减退（唾液分泌减少）。它是头颈部放疗可预见的副作用，且与生活质量的显著受损相关。多种作用机制各异的药物干预措施已被用于预防放射性唾液腺功能障碍。
评估药物干预对预防放射性唾液腺功能障碍的效果。
Cochrane口腔健康信息专家检索了以下数据库：Cochrane口腔健康试验注册库（截至2016年9月14日）；Cochrane图书馆中的Cochrane对照试验中央注册库（CENTRAL；2016年第8期）（检索于2016年9月14日）；MEDLINE Ovid（1946年至2016年9月14日）；Embase Ovid（1980年至2016年9月14日）；CINAHL EBSCO（护理及相关健康文献累积索引；1937年至2016年9月14日）；LILACS BIREME虚拟健康图书馆（拉丁美洲和加勒比健康科学信息数据库；1982年至2016年9月14日）；Zetoc会议论文集（1993年至2016年9月14日）；以及OpenGrey（1997年至2016年9月14日）。我们检索了美国国立卫生研究院正在进行的试验注册库（ClinicalTrials.gov）和世界卫生组织国际临床试验注册平台以查找正在进行的试验。检索电子数据库时对语言或出版日期未设限制。
我们纳入了随机对照试验，无论其出版语言或出版状态如何。试验纳入所有年龄、种族和性别的参与者，计划单独接受放疗或在接受头颈部放疗的同时接受化疗。参与者可以是门诊患者或住院患者。我们纳入了比较任何预防性用于放疗前或放疗期间唾液腺功能障碍的药物方案与安慰剂、无干预或另一种药物干预的试验。排除了放射技术的比较。
我们采用了Cochrane期望的标准方法程序。
我们纳入了39项研究，随机分配了3520名参与者；分析的参与者数量因结局和时间点而异。这些研究被分为14个单独的比较，其中只有3个可以进行荟萃分析。我们发现低质量证据表明，与安慰剂或无治疗对照相比，氨磷汀在放疗结束时（风险比（RR）0.35，95%置信区间（CI）0.19至0.67；P = 0.001，3项研究，119名参与者）以及放疗后长达三个月时（RR 0.66，95% CI 0.48至0.92；P = 0.01，5项研究，687名参与者）可能降低中度至重度口干（0至4级量表上的2级或更高）的风险，但没有足够证据表明这种效果在放疗后12个月仍持续存在（RR 0.70，95% CI 0.40至1.23；P = 0.21，7项研究，682名参与者）。我们发现极低质量证据表明，氨磷汀在放疗后长达12个月时可增加非刺激性唾液流速，无论是每5分钟唾液的毫克数（平均差（MD）0.
