Zeitels Steven M, Barbu Anca M, Landau-Zemer Tali, Lopez-Guerra Gerardo, Burns James A, Friedman Aaron D, Freeman Mason W, Halvorsen Yuan-Di, Hillman Robert E
Department of Surgery, Harvard Medical School, and the Center for Laryngeal Surgery and Voice Rehabilitation the Massachusetts General Hospital Institute of Health Professions, Massachusetts General Hospital, Boston, MA 02114, USA.
Ann Otol Rhinol Laryngol. 2011 Oct;120(10):627-34. doi: 10.1177/000348941112001001.
Photoangiolytic laser treatment of recurrent respiratory papillomatosis (RRP) is effective, but does not reliably prevent recurrence. Therefore, sublesional injections of the antiangiogenic agent bevacizumab (Avastin) were given to assess the adjunctive effect on disease recurrence. Since bevacizumab is a new therapeutic modality for RRP, there were also primary safety objectives to determine whether there was a pegative impact on the voice and whether there were local or systemic complications.
A prospective open-label investigation was conducted in 20 adult patients with bilateral vocal fold RRP. The patients underwent planned 532-nm pulsed KTP laser photoangiolysis of bilateral glottal disease 4 times with an approximately 6-week interval between procedures. At each planned laser procedure, the vocal fold that on initial presentation had a greater volume of disease also underwent 4 serial sublesional bevacizumab injections (7.5 to 12.5 mg in 0.3 to 0.5 mL). A sham injection with saline solution was administered to the other vocal fold as a control. Disease resolution was compared between subjects' vocal folds, and objective measures of vocal function (acoustic, aerodynamic), as well as patients' self-assessments of vocal function (Voice-Related Quality of Life survey), were obtained.
All 20 patients completed the study, and there were no local or systemic complications. After 4 injections, 3 of the 20 patients had no discernible disease in either vocal fold. Of the remaining 17 subjects, 16 had less disease in the bevacizumab-treated vocal fold despite starting with more disease. Only 1 of the 17 had more disease in the bevacizumab-treated vocal fold after 4 injections. Moreover, 7 of the 20 patients (35%) did not require a laser procedure in the vocal fold that had received 4 bevacizumab injections, as compared with 3 of the 20 vocal folds (15%) that were treated with laser alone. All of the vocal function measures displayed statistically significant posttreatment improvements, except for average fundamental frequency in the 3 female patients, in whom it fell below the normal range.
This prospective investigation provided evidence that bevacizumab injections enhanced KTP laser treatment of glottal papillomatosis without systemic or local complications. Coupling the antiangiogenesis agent bevacizumab with KTP laser photoangiolysis is conceptually synergistic and scientifically promising since the mechanisms of action are complementary.
光血管溶解激光治疗复发性呼吸道乳头状瘤病（RRP）是有效的，但不能可靠地预防复发。因此，进行病变内注射抗血管生成药物贝伐单抗（阿瓦斯汀）以评估其对疾病复发的辅助作用。由于贝伐单抗是RRP的一种新治疗方式，还有主要的安全性目标，即确定其是否对嗓音有负面影响以及是否存在局部或全身并发症。
对20例双侧声带RRP成年患者进行前瞻性开放标签研究。患者接受计划的532纳米脉冲KTP激光对双侧声门疾病进行4次光血管溶解治疗，每次治疗间隔约6周。在每次计划的激光治疗时，最初病变体积较大的声带还接受4次连续的病变内贝伐单抗注射（0.3至0.5毫升中含7.5至12.5毫克）。对另一侧声带注射生理盐水作为对照。比较受试者双侧声带的疾病消退情况，并获得嗓音功能的客观指标（声学、空气动力学）以及患者对嗓音功能的自我评估（嗓音相关生活质量调查）。
所有20例患者均完成研究，未出现局部或全身并发症。4次注射后，20例患者中有3例双侧声带均无明显病变。其余17例受试者中，16例在接受贝伐单抗治疗的声带病变较少，尽管最初病变较多。17例中只有1例在4次注射后接受贝伐单抗治疗的声带病变增多。此外，20例患者中有7例（35%）在接受4次贝伐单抗注射处的声带无需进行激光治疗，而单纯接受激光治疗的20例声带中有3例（15%）无需治疗。除3例女性患者的平均基频降至正常范围以下外，所有嗓音功能指标在治疗后均有统计学意义的改善。
这项前瞻性研究证明，贝伐单抗注射增强了KTP激光对声门乳头状瘤病的治疗效果，且无全身或局部并发症。抗血管生成药物贝伐单抗与KTP激光光血管溶解联合应用在概念上具有协同作用，且由于作用机制互补，在科学上具有前景。
