Interventions for the prevention and treatment of herpes simplex virus in patients being treated for cancer

 

Abstract

Background

Treatment of cancer is increasingly effective, but associated with oral complications such as mucositis, fungal infections, bacterial infections and viral infections such as the herpes simplex virus (HSV).

Objectives

To examine the effects of interventions for the prevention or treatment or both, of herpes simplex virus in patients receiving treatment for cancer.

Search methods

We searched the following databases: Cochrane Oral Health Group's Trials Register, CENTRAL, MEDLINE, EMBASE, CINAHL, CANCERLIT, SIGLE and LILACS. The reference list of all related review articles and articles considered to be potentially relevant were checked for further trials. Authors of identified trials and known specialists in the field were also contacted in an attempt to identify any additional published or unpublished trials. Date of most recent search: November 2008.

Selection criteria

All randomised controlled trials comparing interventions for the prevention or treatment or both of HSV infection in people being treated for cancer. Outcomes were presence/absence of clinical/culture positive HSV infections (prevention), time to complete healing of lesions (treatment), duration of viral shedding, recurrence of lesions, relief of pain, amount of analgesia, duration of hospital stay, cost of oral care, patient quality of life and adverse effects.

Data collection and analysis

Data were independently extracted, in duplicate, by two review authors. Authors were contacted for details of randomisation, blindness and sample demographics where necessary. Quality assessment was carried out on randomisation, blindness, withdrawals and selective reporting. The Cochrane Collaboration's statistical guidelines were followed and risk ratio (RR) values were calculated using random-effects models.

Main results

Seventeen trials satisfied the inclusion criteria. Four trials evaluated preventative interventions for HSV lesions, three trials for viral isolates, and eight trials evaluated both outcome measures. A single trial reported on the cost of prophylaxis for HSV. Two trials evaluating treatment reported on time to healing, duration of viral shedding and relief of pain. No trials reported on duration of hospital stay, amount of analgesia or patient quality of life.

In placebo controlled trials, aciclovir was found to be effective for the prevention of HSV infections as measured by oral lesions or viral isolates (RR = 0.16, 95% confidence interval (CI) 0.08 to 0.31 nine trials; RR = 0.17, 95% CI 0.07 to 0.37 nine trials). There is no evidence that valaciclovir is more efficacious than aciclovir, or that higher doses of valaciclovir are more effective than lower doses. Placebo was found to be more effective than prostaglandin E for prevention of viral isolates (RR = 1.87, 95% CI 1.12 to 3.14 one trial).

Aciclovir was also found to be effective for the treatment of HSV in terms of duration of viral shedding (median of 2.5 days versus 17.0 days, P = 0.0002; 2 days compared to more than 9, P = 0.0008), time to first decrease in pain (median 3 days compared to 16, P = 0.04), complete resolution of pain (9.9 days compared to 13.6 days, P = 0.01; median of 6 days compared to 16, P = 0.05), 50% healing (median of 6 days compared to 11, P = 0.01) and total healing (median 13.9 days compared to 20.7 days, P = 0.08; median of 8 days compared to 21, P = 0.0).

Authors' conclusions

There is evidence that aciclovir is efficacious in the prevention and treatment of herpes simplex virus infections. There is no evidence that valaciclovir is more efficacious than aciclovir, or that a high dose of valaciclovir is better than a low dose of valaciclovir. There is evidence that as a prophylaxis, placebo is more efficacious than prostaglandin E. However, in all included trials, risk of bias is unclear.

 

Plain language summary

Interventions for the prevention and treatment of herpes simplex virus in patients being treated for cancer

Treatment of cancer is increasingly effective, but associated with oral complications such as mucositis, fungal infections, bacterial infections and viral infections such as the herpes simplex virus (HSV). Oral complications can impact severely on quality of life and may lead to life-threatening systemic infection. Infection with HSV can cause pain and blistering on or around the lips and within the mouth. Orofacial lesions are most commonly caused by HSV type 1. Aciclovir and other antiviral drugs such as valaciclovir, famiciclovir and penciclovir, have been widely used to treat HSV-related conditions. Recurrent HSV type 1 infection in patients who are immunocompromised due to treatment for cancer may be more aggressive, painful and slower to heal. These more extensive lesions often require much longer treatment and leave the patient more susceptible to developing drug-resistant strains of HSV. This review of 17 trials found evidence that aciclovir is efficacious in the prevention and treatment of HSV infections, in terms of preventing clinical/culture positive HSV infections, reduction in healing time, duration of viral shedding and relief of pain. There is no evidence that valaciclovir is more efficacious than aciclovir, or that a high dose of valaciclovir is better than a low dose of valaciclovir. There is evidence that for prevention, placebo is more efficacious than prostaglandin E. However, in all included trials, risk of bias is unclear. No trials reported on duration of hospital stay, amount of analgesia or patient quality of life.

 

摘要

背景

預防與治療發生在已治療的癌症病人身上的簡單皰疹病毒

癌症的治療越來越有效果，但仍有相關的口腔併發症如粘膜炎、黴菌感染、細菌或病毒感染如簡單皰疹病毒感染。

目標

為了檢視用於接受癌症治療病人身上,預防與治療簡單皰疹病毒方法的效果

搜尋策略

我們從以下的資料庫獲得資料：Cochrane Oral Health Group's Trials Register, CENTRAL, MEDLINE, EMBASE, CINAHL, CANCERLIT, SIGLE and LILACS。我們閱讀了相關的回顧型文獻或其他可能有相關的文獻，並且聯絡了相關領域的專家以了解更多的資訊或未公開發表的資訊。最新資料：2008年11月。

選擇標準

蒐集所有比較預防或治療癌症病人身上的簡單皰疹病毒的隨機對照試驗。觀察的資訊有：存在或不存在臨床或培養出簡單皰疹病毒(預防方面)、治癒的時間(治療方面)、病毒脫落的時間、病灶再發的有無、疼痛緩解、止痛藥之劑量、住院天數、口腔照護的花費、病人的生活品質以及藥物副作用。

資料收集與分析

所有的資料由兩位作者獨立回顧，並且聯絡文獻作者以得知隨機分布、盲目測試與統計分析的細節。我們遵循 The Cochrane Collaboration's statistical guidelines並使用隨機效果模式來計算風險比(risk ratio)。

主要結論

17個試驗符合資料納入條件，4個試驗評估了簡單皰疹病毒的預防方法，3個試驗分離出病毒，8個試驗分析了預防與治療的情形，1個試驗指出了簡單皰疹病毒預防的花費，2個試驗指出了癒合時間、病毒脫落的時間和疼痛緩解的情形。沒有試驗指出住院天數、止痛藥的劑量或病人的生活品質。在安慰劑對照試驗中，在口腔病灶的測量或分離出的病毒量上，aciclovir都有良好的治療效果(RR = 0.16, 95% confidence interval (CI) 0.08 to 0.31 nine trials; RR = 0.17, 95% CI 0.07 to 0.37 nine trials)。沒有證據顯示valaciclovir比aciclovir有效果，或是高劑量的valaciclovir比低劑量的valaciclovir有效。在簡單皰疹病毒的預防方面，安慰劑則比prostaglandin E有效(RR = 1.87, 95% CI 1.12 to 3.14 one trial)。Aciclovir在治療簡單皰疹病毒是有效的，無論是在病毒脫落的時間(平均2.5天比17天， P = 0.0002; 2比9天以上, P = 0.0008)、第一次疼痛緩解的時間(3天比16天，P = 0.04)、疼痛完全緩解的時間(9.9天比13.6天，P = 0.01; 平均6天比16天, P = 0.05)、半數治癒率(平均6天比11天， P = 0.01)與完全治癒的天數(平均13.9天比20.7天， P = 0.08; 平均8天比21天, P = 0.0)，都比對照組有較好的效果。

作者結論

證據顯示aciclovir在預防與治療簡單皰疹病毒上是有效果的。沒有證據顯示valaciclovir比aciclovir有效果，或是高劑量的valaciclovir比低劑量的valaciclovir有效。在簡單皰疹病毒的預防方面，安慰劑則比prostaglandin E有效。然而，在所有的試驗中，有關資料偏差(bias)並不清楚。。

翻譯人

本摘要由臺灣大學附設醫院鄭翔元翻譯。

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

總結

癌症的治療越來越有效果，但仍有相關的口腔併發症如粘膜炎、黴菌感染、細菌或病毒感染如簡單皰疹病毒感染。口腔併發症會降低病人的生活品質，並可能引起致命的全身性感染。簡單皰疹病毒感染可能引起疼痛或在唇部或口腔產生水泡。口腔顏面部的病灶通常是由第一型簡單皰疹病毒引起。Aciclovir和其他抗病毒感染的藥物如valaciclovir、famiciclovir和penciclovir被廣泛用於簡單皰疹病毒的治療。在一些免疫低下的病人身上，反覆的簡單皰疹病毒感染可能會較於嚴重，比較疼痛或是癒合速度較慢。這些較廣泛的病灶通常需要比較長的治療時間，並且比較可能產生有抗藥性的皰疹病毒。這篇文獻回顧了17個試驗，證據顯示aciclovir在預防與治療簡單皰疹病毒上是有效果的，無論是在預防臨床或培養出皰疹病毒、減少癒合時間或減少病毒脫落或疼痛緩解的時間都有良好表校。沒有證據顯示valaciclovir比aciclovir有效果，或是高劑量的valaciclovir比低劑量的valaciclovir有效。在簡單皰疹病毒的預防方面，安慰劑則比prostaglandin E有效。然而，在所有的試驗中，資料偏差是不清楚的。沒有試驗指出住院天數、止痛藥的劑量或病人的生活品質。