Haffty Bruce G, Wilson Lynn D, Son Yung H, Cho Edward I, Papac Rose J, Fischer Diana B, Rockwell Sara, Sartorelli Alan C, Ross Douglas A, Sasaki Clarence T, Fischer James J
Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Int J Radiat Oncol Biol Phys. 2005 Jan 1;61(1):119-28. doi: 10.1016/j.ijrobp.2004.07.730.
Previous randomized trials have shown a benefit with concurrent use of the hypoxic cell cytotoxin mitomycin C (MC) and radiation (RT) in the management of squamous cell cancer of the head and neck (SCCHN). We conducted a randomized trial comparing MC with porfiromycin (POR) in combination with RT in the management of SCCHN.
Between 1992 and 1999, 128 patients with SCCHN were enrolled in this prospective randomized trial. Patients were stratified by management intent, and balanced with respect to stage and site of disease. They were randomized to receive MC (15 mg/M(2)) or POR (40 mg/M(2)) on Days 5 and 47 (or last day) of RT. Of 121 evaluable patients, 61 were randomized to MC and 60 to POR. Patients were treated with standard daily RT to a total median dose of 64 Gy over 47 days. Patients were well balanced with respect to management intent, stage, site, age, sex, hemoglobin levels, tumor grade, radiation dose, and days on treatment.
There were no significant differences between the two arms with respect to acute hematologic or nonhematologic toxicities. As of January 2003 with a median follow-up of 6.3 years, there have been 19 local relapses (4 MC vs. 15 POR), 21 regional relapses (7 MC vs. 14 POR), 24 distant metastases (11 MC vs. 13 POR), and 66 deaths (33 MC vs. 33 POR). MC was superior to POR with respect to 5-year local relapse-free survival (91.6% vs. 72.7%, p = 0.01), local-regional relapse-free survival (82% vs. 65.3%, p = 0.05), and disease-free survival (72.8% vs. 52.9%, p = 0.026). There were no significant differences between the two arms with respect to overall survival (49.2% vs. 54.4%) or distant metastasis-free rate (79.9% vs. 75.9%).
Despite promising preclinical data, and an acceptable toxicity profile, POR was inferior to MC as an adjunct to RT in the management of SCCHN. This randomized trial emphasizes the need for randomized studies to evaluate new agents in the management of SCCHN.
既往随机试验表明，在头颈部鳞状细胞癌（SCCHN）的治疗中，同时使用乏氧细胞细胞毒素丝裂霉素C（MC）和放疗（RT）具有益处。我们开展了一项随机试验，比较MC与卟吩姆钠（POR）联合RT治疗SCCHN的效果。
1992年至1999年期间，128例SCCHN患者纳入了这项前瞻性随机试验。患者按治疗意向分层，并在疾病分期和部位方面保持均衡。他们被随机分配在放疗的第5天和第47天（或最后一天）接受MC（15 mg/M²）或POR（40 mg/M²）治疗。在121例可评估患者中，61例被随机分配至MC组，60例被随机分配至POR组。患者接受标准的每日放疗，在47天内总中位剂量达64 Gy。患者在治疗意向、分期、部位、年龄、性别、血红蛋白水平、肿瘤分级、放疗剂量和治疗天数方面保持良好均衡。
两组在急性血液学或非血液学毒性方面无显著差异。截至2003年1月，中位随访6.3年，有19例局部复发（MC组4例 vs. POR组15例），21例区域复发（MC组7例 vs. POR组14例），24例远处转移（MC组11例 vs. POR组13例），66例死亡（MC组33例 vs. POR组33例）。在5年局部无复发生存率（91.6% vs. 72.7%，p = 0.01）、局部区域无复发生存率（82% vs. 65.3%，p = 0.05）和无病生存率（72.8% vs. 52.9%，p = 0.026）方面，MC优于POR。两组在总生存率（49.2% vs. 54.4%）或无远处转移率（79.9% vs. 75.9%）方面无显著差异。
尽管临床前数据令人鼓舞且毒性可接受，但在SCCHN的治疗中，作为放疗的辅助手段，POR不如MC。这项随机试验强调了开展随机研究以评估SCCHN治疗新药物的必要性。
