Best Simon R, Friedman Aaron D, Landau-Zemer Tali, Barbu Anca M, Burns James A, Freeman Mason W, Halvorsen Yuan-Di, Hillman Robert E, Zeitels Steven M
Department of Surgery, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts, USA.
Ann Otol Rhinol Laryngol. 2012 Sep;121(9):587-93. doi: 10.1177/000348941212100905.
Increasing evidence supports the use of laryngeal injections of the antiangiogenic agent bevacizumab (Avastin) for the adjuvant treatment of recurrent respiratory papillomatosis (RRP). A recent prospective open-label investigation, approved by the US Food and Drug Administration, employing 12.5 mg of sublesional bevacizumab demonstrated single-site efficacy without complications; however, the safety of multiple-site injections and higher dosing has not yet been reported. The primary objective of this study was to report on the safety of increased doses of bevacizumab for the treatment of RRP.
Two cohorts of adult patients were evaluated. In the first group, a prospective analysis was performed on patients with a diagnosis of laryngeal RRP after t heir participation in th e initial clinical trial with a single-site lowerdose (7.5 to 12.5 mg). They received higher doses of sublesional laryngeal bevacizumab (15 to 50 mg total) with detailed physiologic, hematologic, and serum chemistry measurements performed before and after each bevacizumab injection. A second cohort of patients received sublesional laryngeal injections of bevacizumab (15 to 88 mg total) without physiologic measurements and underwent a retrospective analysis of reported complications.
One hundred consecutive laryngeal injection sessions (office, 87; operating room, 13) with bevacizumab were performed in 43 patients, with a mean dose of 30 mg total per treatment (range, 15 to 88 mg). Sixty-three of the 100 sessions were accompanied by KTP laser photoangiolysis of the papilloma prior to bevacizumab injections. Eighteen patients (cohort 1) underwent detailed physiologic assessment, and no dysfunction was observed. There were no local or systemic complications of bevacizumab administration. The second group of 25 patients (cohort 2) also reported no significant local or systemic complications. Neither patient group was observed to have a local wound problem in the larynx.
This investigation provides evidence that higher doses of bevacizumab are relatively safe in adult patients with laryngeal RRP. Further refinements in pharmacologic concentration and drug delivery will determine the optimal treatment regimens in the future.
越来越多的证据支持使用抗血管生成药物贝伐单抗（阿瓦斯汀）进行喉部注射，用于复发性呼吸道乳头状瘤病（RRP）的辅助治疗。美国食品药品监督管理局批准的一项近期前瞻性开放标签研究，采用12.5mg瘤下注射贝伐单抗，显示出单部位疗效且无并发症；然而，多部位注射及更高剂量的安全性尚未见报道。本研究的主要目的是报告增加剂量的贝伐单抗治疗RRP的安全性。
对两组成年患者进行评估。第一组，对参与初始单部位低剂量（7.5至12.5mg）临床试验后诊断为喉部RRP的患者进行前瞻性分析。他们接受更高剂量的瘤下喉部贝伐单抗（总量15至50mg），每次贝伐单抗注射前后进行详细的生理、血液学和血清化学测量。第二组患者接受瘤下喉部注射贝伐单抗（总量15至88mg），未进行生理测量，并对报告的并发症进行回顾性分析。
43例患者共进行了100次连续的贝伐单抗喉部注射（门诊87次，手术室13次），每次治疗的平均总剂量为30mg（范围15至88mg）。100次注射中有63次在注射贝伐单抗前伴有KTP激光对乳头状瘤进行光血管溶解。18例患者（第一组）接受了详细的生理评估，未观察到功能障碍。贝伐单抗给药未出现局部或全身并发症。第二组25例患者（第二组）也未报告明显的局部或全身并发症。两组患者均未观察到喉部局部伤口问题。
本研究提供的证据表明，更高剂量的贝伐单抗在成年喉部RRP患者中相对安全。未来，药物浓度和给药方式的进一步优化将确定最佳治疗方案。
