Shehab Nadine, Sweet Burgunda V, Hogikyan Norman D
Department of Pharmacy Services, University of Michigan Health System, University Hospital, Ann Arbor, Michigan 48109-0008, USA.
Pharmacotherapy. 2005 Jul;25(7):977-89. doi: 10.1592/phco.2005.25.7.977.
Recurrent respiratory papillomatosis (RRP) is a rare but potentially severe disease caused by papillomavirus, most often types 6 and 11. The disease, which occurs in both juvenile and adult forms, is characterized by benign epithelial tumors of the airway that most frequently affect the larynx but can also spread along the entire aerodigestive tract. Recurrent respiratory papillomatosis is the most common benign neoplasm of the larynx in children and the second most frequent cause of childhood hoarseness. Standard treatment, which is palliative only, consists of surgical excision of papillomata to maintain airway patency and improve voice quality. Recurrence despite repeated surgical procedures is the rule. To date, incorporation of adjuvant treatments has not been reliably beneficial in altering the disease course. Several case series have described promising results with cidofovir, a cytosine nucleoside analog with antiviral activity. To evaluate the data available on the safety and efficacy of cidofovir for the treatment of RRP, we conducted a MEDLINE search for all case reports or series from January 1966-August 2004 describing cidofovir therapy in either adults or children with RRP. The bibliographies of qualifying articles were also searched for relevant references. In both adults and children with mild-to-severe RRP, intralesional administration of cidofovir directly into the site of papillomata was associated with partial-to-complete regression of papillomata, improvement in voice quality and airway status, and decreased need for surgery. Wide variation in intralesional cidofovir dose (2-57 mg), frequency (every 2-8 wks), and duration (4 mo-4 yrs) was found. Successful outcomes have also been reported with intravenous cidofovir, but data are limited to three case reports. Rash, headache, and precordialgia were the only adverse effects reported with intralesional cidofovir. Nephrotoxicity and neutropenia secondary to either intralesional or intravenous cidofovir were not observed. Long-term risks associated with intralesional administration remain to be seen. Further studies are necessary to determine the most appropriate dose, frequency, and duration of therapy, and to fully characterize the safety profile profile of cidofovir when given intralesionally.
复发性呼吸道乳头状瘤病（RRP）是一种由乳头瘤病毒引起的罕见但可能严重的疾病，最常见的是6型和11型。该疾病有青少年和成人两种形式，其特征是气道的良性上皮肿瘤，最常影响喉部，但也可沿整个气消化道扩散。复发性呼吸道乳头状瘤病是儿童中最常见的喉部良性肿瘤，也是儿童声音嘶哑的第二大常见原因。标准治疗仅为姑息性治疗，包括手术切除乳头状瘤以维持气道通畅并改善声音质量。尽管反复进行手术，但复发是常有的事。迄今为止，辅助治疗的加入在改变疾病进程方面尚未被证实有可靠的益处。几个病例系列报道了西多福韦（一种具有抗病毒活性的胞嘧啶核苷类似物）取得了有希望的结果。为了评估有关西多福韦治疗RRP的安全性和有效性的现有数据，我们对1966年1月至2004年8月期间所有描述西多福韦治疗成人或儿童RRP的病例报告或系列进行了MEDLINE检索。对符合条件文章的参考文献也进行了相关参考文献的检索。在患有轻至重度RRP的成人和儿童中，将西多福韦直接注射到乳头状瘤部位进行病灶内给药与乳头状瘤部分至完全消退、声音质量和气道状况改善以及手术需求减少有关。发现病灶内西多福韦剂量（2 - 57毫克）、频率（每2 - 8周）和持续时间（4个月 - 4年）存在很大差异。静脉注射西多福韦也有成功治疗的报道，但数据仅限于3例病例报告。病灶内注射西多福韦报告的唯一不良反应是皮疹、头痛和心前区疼痛。未观察到病灶内或静脉注射西多福韦继发的肾毒性和中性粒细胞减少。病灶内给药相关的长期风险仍有待观察。需要进一步研究以确定最合适的治疗剂量、频率和持续时间，并充分描述病灶内注射西多福韦时的安全性概况。
