Clarkson J E, Worthington H V, Eden O B
Dental Health Services Research Unit, University of Dundee Dental Hospital and School, Park Place, Dundee, UK, DD1 4HN.
Cochrane Database Syst Rev. 2000(2):CD000978. doi: 10.1002/14651858.CD000978.
Treatment of cancer with chemotherapy is becoming increasingly more effective but is associated with short and long-term side effects. Oral side effects remain a major source of illness despite the use of a variety of agents to prevent them.
To evaluate the effectiveness of oral (and topical) prophylactic agents for oral mucositis and oral candidiasis in patients with cancer (excluding head and neck cancer), compared with placebo or no treatment.
Computerised MEDLINE, EMBASE, CINAHL, CANCERLIT, the Cochrane Controlled Trials Register and the Cochrane Oral Health Group Specialist Register search up to July 1999. Reference lists from relevant articles were scanned and the authors of eligible studies were contacted to identify trials and obtain additional information.
Studies were selected if they met the following criteria: design - random or quasi-random allocation of participants; participants - anyone with cancer receiving chemotherapy (excluding head and neck cancer); interventions - prophylactic agents prescribed to reduce oral conditions arising from cancer or its treatment; outcomes - mucositis and oral candidiasis.
Information regarding methods, participants, interventions and outcome measures and results were independently extracted, in duplicate, by two reviewers (JC & HW). Specialist advice was sought to categorise interventions. Authors were contacted for details of randomisation and withdrawals and a quality assessment was carried out using the Jadad criteria (Jadad 1998). The Cochrane Oral Health Group statistical guidelines were followed and relative risk values calculated using random effects models where significant heterogeneity was detected (P < 0.1).
Thirty-eight reports of trials were initially included. Two were duplicate reports and nine were excluded as there was no useable information. Of the 27 useable studies 14 had data for mucositis comprising 945 randomised patients and 15 included data for oral candidiasis with 1164 randomised patients. Of the eight prophylactic agents used for mucositis only one, ice chips, was effective (Relative risk 0.57, 95% CI 0.43 to 0.77, chi-square for heterogeneity = 0.26 (df = 1), p = 0.61). The NNT to prevent one extra case of mucositis over the baseline incidence using ice chips was 4 (95%CI: 3 to 7). The NNT for when the baseline incidence of mucositis in the population ranges from 50% to 80% are 5 to 4 respectively. There is evidence that antifungal agents which are partially or fully absorbed from the gastrointestinal tract prevent oral candidiasis and that the partially absorbed agents may be more effective than the fully absorbed agents. The RR for partially absorbed agents was 0.13 (95% CI 0.06 to 0.27, chi-square for heterogeneity = 5.3 (df = 3), P = 0. 15). The NNT to prevent one extra case of oral candidiasis over the baseline incidence using partially absorbed drugs was 3 (95% CI: 3 to 5). The NNT for when the baseline incidence of oral candidiasis in the population ranges from 30% to 70% are 4 to 2 respectively. The general reporting of RCT's was poor however the median Jadad score was acceptable and improved further when the authors provided additional information. The sensitivity analysis confirmed the findings for oral candidiasis.
REVIEWER'S CONCLUSIONS: There is some evidence that ice chips prevent mucositis. None of the other prophylactic agents included in this review prevented mucositis. There is evidence that prophylactic use of antifungal agents which are absorbed or partially absorbed from the gastrointestinal tract reduce the clinical signs of oral candidiasis, and the partially absorbed drugs may be more effective. Future trials in this area should address the link between oral and general health including outcomes relevant to the patient. Collaboration between medical and dental teams is indicated.
化疗治疗癌症的效果日益显著，但会带来短期和长期的副作用。尽管使用了多种药物来预防，但口腔副作用仍是主要的患病根源。
评估口服（及局部用）预防药物对癌症患者（不包括头颈癌）口腔黏膜炎和口腔念珠菌病的有效性，并与安慰剂或不治疗进行比较。
检索截至1999年7月的计算机化医学文献数据库（MEDLINE）、荷兰医学文摘数据库（EMBASE）、护理学与健康领域数据库（CINAHL）、癌症文献数据库（CANCERLIT）、Cochrane对照试验注册库以及Cochrane口腔健康小组专业注册库。查阅相关文章的参考文献列表，并联系符合条件研究的作者以识别试验并获取更多信息。
符合以下标准的研究被纳入：设计——参与者随机或准随机分配；参与者——任何接受化疗的癌症患者（不包括头颈癌）；干预措施——开具预防药物以减少癌症或其治疗引起的口腔问题；结局指标——口腔黏膜炎和口腔念珠菌病。
两名审阅者（JC和HW）独立、重复地提取有关方法、参与者、干预措施、结局指标及结果的信息。寻求专家建议以对干预措施进行分类。联系作者获取随机分组和退出的详细信息，并使用Jadad标准（Jadad，1998年）进行质量评估。遵循Cochrane口腔健康小组的统计指南，在检测到显著异质性（P<0.1）时使用随机效应模型计算相对风险值。
最初纳入了38篇试验报告。其中2篇为重复报告，9篇因无可用信息而被排除。在27项可用研究中，14项有口腔黏膜炎的数据，涉及945名随机分组患者；15项有口腔念珠菌病的数据，涉及1164名随机分组患者。用于口腔黏膜炎的8种预防药物中，只有碎冰有效（相对风险0.57，95%置信区间0.43至0.77，异质性卡方值=0.26（自由度=1），P=0.61）。使用碎冰预防口腔黏膜炎超过基线发病率时，预防一例额外病例所需的治疗人数（NNT）为4（95%置信区间：3至7）。当人群中口腔黏膜炎的基线发病率在50%至80%之间时，NNT分别为5至4。有证据表明，从胃肠道部分或完全吸收的抗真菌药物可预防口腔念珠菌病，且部分吸收的药物可能比完全吸收的药物更有效。部分吸收药物的相对风险为0.13（95%置信区间0.06至0.27，异质性卡方值=5.3（自由度=3），P=0.15）。使用部分吸收药物预防口腔念珠菌病超过基线发病率时，预防一例额外病例所需的治疗人数为3（95%置信区间：3至5）。当人群中口腔念珠菌病的基线发病率在30%至70%之间时，NNT分别为4至2。随机对照试验的总体报告质量较差，但Jadad评分中位数可接受，当作者提供更多信息时评分进一步提高。敏感性分析证实了口腔念珠菌病的研究结果。
有证据表明碎冰可预防口腔黏膜炎。本综述中纳入的其他预防药物均不能预防口腔黏膜炎。有证据表明，预防性使用从胃肠道吸收或部分吸收的抗真菌药物可减轻口腔念珠菌病的临床症状，且部分吸收的药物可能更有效。该领域未来的试验应关注口腔健康与整体健康之间的联系，包括与患者相关的结局。建议医疗团队和牙科团队开展协作。
