Garg Madhur K, Zhao Fengmin, Sparano Joseph A, Palefsky Joel, Whittington Richard, Mitchell Edith P, Mulcahy Mary F, Armstrong Karin I, Nabbout Nassim H, Kalnicki Shalom, El-Rayes Bassel F, Onitilo Adedayo A, Moriarty Daniel J, Fitzgerald Thomas J, Benson Al B
Madhur K. Garg, Joseph A. Sparano, and Shalom Kalnicki, Montefiore Medical Center, Albert Einstein College of Medicine, Montefiore-Einstein Center for Cancer Care, Bronx, NY; Fengmin Zhao, Dana Farber Cancer Institute, Boston, MA; Joel Palefsky, University of California, San Francisco, CA; Richard Whittington, Philadelphia VA Medical Center; Edith P. Mitchell, Thomas Jefferson University, Philadelphia, PA; Mary F. Mulcahy and Al B. Benson III, Northwestern University, Chicago, IL; Karin I. Armstrong, United Hospital, Woodbury, MN; Nassim H. Nabbout, Cancer Center of Kansas, Wichita, KS; Bassel F. El-Rayes, Emory University, Atlanta, GA; Adedayo A. Onitilo, Marshfield Clinic, Marshfield, WI; Daniel J. Moriarty, Overlook Medical Center, Summit, NJ; and Thomas J. Fitzgerald, Imaging and Radiation Oncology Core, Quality Assurance Review Center, Providence, RI.
J Clin Oncol. 2017 Mar;35(7):718-726. doi: 10.1200/JCO.2016.69.1667. Epub 2017 Jan 9.
Purpose Squamous cell carcinoma of the anal canal (SCCAC) is characterized by high locoregional failure (LRF) rates after sphincter-preserving definitive chemoradiation (CRT) and is typically associated with anogenital human papilloma virus infection. Because cetuximab enhances the effect of radiation therapy in human papilloma virus-associated oropharyngeal squamous cell carcinoma, we hypothesized that adding cetuximab to CRT would reduce LRF in SCCAC. Methods Sixty-one patients with stage I to III SCCAC received CRT including cisplatin, fluorouracil, and radiation therapy to the primary tumor and regional lymph nodes (45 to 54 Gy) plus eight once-weekly doses of concurrent cetuximab. The study was designed to detect at least a 50% reduction in 3-year LRF rate (one-sided α, 0.10; power 90%), assuming a 35% LRF rate from historical data. Results Poor risk features included stage III disease in 64% and male sex in 20%. The 3-year LRF rate was 23% (95% CI, 13% to 36%; one-sided P = .03) by binomial proportional estimate using the prespecified end point and 21% (95% CI, 7% to 26%) by Kaplan-Meier estimate in a post hoc analysis using methods consistent with historical data. Three-year rates were 68% (95% CI, 55% to 79%) for progression-free survival and 83% (95% CI, 71% to 91%) for overall survival. Grade 4 toxicity occurred in 32%, and 5% had treatment-associated deaths. Conclusion Although the addition of cetuximab to chemoradiation for SCCAC was associated with lower LRF rates than historical data with CRT alone, toxicity was substantial, and LRF still occurs in approximately 20%, indicating the continued need for more effective and less toxic therapies.
目的 肛管鳞状细胞癌（SCCAC）的特征是在保留括约肌的根治性放化疗（CRT）后局部区域复发（LRF）率高，且通常与肛门生殖器人乳头瘤病毒感染有关。由于西妥昔单抗可增强放疗对人乳头瘤病毒相关口咽鳞状细胞癌的疗效，我们推测在CRT中加入西妥昔单抗可降低SCCAC的LRF。方法 61例I至III期SCCAC患者接受CRT，包括顺铂、氟尿嘧啶，并对原发肿瘤和区域淋巴结进行放疗（45至54 Gy），外加每周一次共8剂的西妥昔单抗。该研究旨在检测3年LRF率至少降低50%（单侧α = 0.10；检验效能90%），假设根据历史数据LRF率为35%。结果 不良风险特征包括64%为III期疾病，20%为男性。使用预先设定的终点通过二项式比例估计，3年LRF率为23%（95%CI，13%至36%；单侧P = 0.03），在使用与历史数据一致的方法进行的事后分析中，通过Kaplan-Meier估计为21%（95%CI，7%至26%）。无进展生存率的3年率为68%（95%CI，55%至79%），总生存率的3年率为83%（95%CI，71%至91%）。4级毒性发生率为32%，5%有与治疗相关的死亡。结论 虽然在SCCAC的放化疗中加入西妥昔单抗与单独使用CRT的历史数据相比LRF率较低，但毒性很大，且LRF仍约有20%发生，这表明仍持续需要更有效且毒性更小的治疗方法。
