Davies A N, Shorthose K
Royal Marsden Hospital, Department of Palliative Medicine, Downs Road, Sutton, Surrey, UK, SM2 5PT.
Cochrane Database Syst Rev. 2007 Jul 18(3):CD003782. doi: 10.1002/14651858.CD003782.pub2.
Salivary gland dysfunction is a predictable side effect of radiotherapy to the head and neck region. Pilocarpine hydrochloride (a choline ester) is licensed in many countries for the treatment of radiation-induced salivary gland dysfunction. Other parasympathomimetics have also been used 'off licence' in the treatment of this condition.
To determine the efficacy and tolerability of parasympathomimetic drugs in the treatment of radiation-induced salivary gland dysfunction.
A detailed search strategy was developed for MEDLINE, and adapted for other databases (Cochrane Pain, Palliative and Supportive Care Group Register; Cochrane Oral Health Group Register; The Cochrane Controlled Trials Register; EMBASE; CINAHL; SIGLE; Dissertation Abstracts). The reference lists of identified studies, review articles and radiotherapy textbooks were checked for additional studies. Relevant pharmaceutical companies, clinical investigators, and professional organizations/journals were also contacted about additional studies.
The selection criteria for the review were: 1) randomised controlled trials; 2) patients suffering from radiation-induced salivary gland dysfunction; 3) patients treated with parasympathomimetic drugs; and 4) assessable data available on primary outcome measures.
The two review authors independently collected data from the full text version of relevant papers including: 1) citation details; 2) patients; 3) interventions; 4) assessments; 5) outcomes (i.e. efficacy, tolerability); and 6) quality issues. We were unable to perform a meta-analysis, due to a lack of appropriate data.
Only three studies, involving a total of 298 patients, fulfilled the entry criteria for the review. All three studies involved the use of pilocarpine hydrochloride. The data suggest that pilocarpine hydrochloride was more effective than placebo, and at least as effective as artificial saliva in those participants that responded. The response rate was 42 to 51%. The time to response was up to 12 weeks. The side effect rate was high, and side effects were the main reason for withdrawal (six to 15% patients taking 5 mg tds). The side effects were usually the result of generalised parasympathomimetic stimulation (e.g. sweating, headaches, urinary frequency, vasodilatation). Response rates were not dose dependent, but side effect rates were dose dependent.
AUTHORS' CONCLUSIONS: There is limited evidence to support the use of pilocarpine hydrochloride in the treatment of radiation-induced salivary gland dysfunction. Currently, there is little evidence to support the use of other parasympathomimetic drugs in the treatment of this condition. Available studies suggest approximately half of patients will respond, but side effects to responders can be problematic. Adverse effects are dose dependent therefore it is important to keep dose to 5 mg tds.
唾液腺功能障碍是头颈部放疗可预见的副作用。盐酸毛果芸香碱（一种胆碱酯）在许多国家被批准用于治疗放射性唾液腺功能障碍。其他拟副交感神经药也被“违规”用于治疗这种疾病。
确定拟副交感神经药治疗放射性唾液腺功能障碍的疗效和耐受性。
为MEDLINE制定了详细的检索策略，并适用于其他数据库（Cochrane疼痛、姑息和支持治疗组注册库；Cochrane口腔健康组注册库；Cochrane对照试验注册库；EMBASE；CINAHL；SIGLE；学位论文摘要）。检查已识别研究、综述文章和放疗教科书的参考文献列表以查找其他研究。还就其他研究联系了相关制药公司、临床研究人员以及专业组织/期刊。
该综述的选择标准为：1）随机对照试验；2）患有放射性唾液腺功能障碍的患者；3）接受拟副交感神经药治疗的患者；4）主要结局指标有可评估数据。
两位综述作者独立从相关论文的全文版本中收集数据，包括：1）引用细节；2）患者；3）干预措施；4）评估；5）结局（即疗效、耐受性）；6）质量问题。由于缺乏适当数据，我们无法进行荟萃分析。
只有三项研究共纳入298例患者，符合该综述的纳入标准。所有三项研究均使用了盐酸毛果芸香碱。数据表明，盐酸毛果芸香碱比安慰剂更有效，在有反应的参与者中至少与人工唾液一样有效。反应率为42%至51%。起效时间长达12周。副作用发生率高，且副作用是停药的主要原因（6%至15%服用5毫克每日三次的患者）。副作用通常是全身性拟副交感神经刺激的结果（如出汗、头痛、尿频、血管扩张）。反应率与剂量无关，但副作用发生率与剂量有关。
有有限证据支持使用盐酸毛果芸香碱治疗放射性唾液腺功能障碍。目前，几乎没有证据支持使用其他拟副交感神经药治疗这种疾病。现有研究表明约一半患者会有反应，但有反应者的副作用可能是个问题。不良反应与剂量有关，因此将剂量保持在5毫克每日三次很重要。
