Arnold Susanne M, Regine William F, Ahmed Mansoor M, Valentino Joseph, Spring Paul, Kudrimoti Mahesh, Kenady Daniel, Desimone Philip, Mohiuddin Mohammed
Department of Medicine, University of Kentucky Markey Cancer Center, Lexington 40536, USA.
Int J Radiat Oncol Biol Phys. 2004 Apr 1;58(5):1411-7. doi: 10.1016/j.ijrobp.2003.09.019.
Current therapies for locally advanced squamous cell carcinoma of the head and neck (SCCHN) result in 50% long-term remission. Low-dose radiotherapy (<100 cGy) induces enhanced cell killing in vitro via the hyper-radiation sensitivity phenomenon but has not been used in the clinical setting. On the basis of the demonstrated synergy between chemotherapy and low-dose fractionated RT, a novel neoadjuvant therapy was designed using low-dose fractionated RT as a chemopotentiator for locally advanced SCCHN.
Forty patients with locally advanced SCCHN received paclitaxel (225 mg/m2), carboplatin (area under the curve of 6), and four 80-cGy fractions of radiotherapy (two each on Days 1 and 2). This sequence was repeated on Days 22 and 23.
Of the 40 patients enrolled, 39 were assessable. Grade 3 or worse toxicities included neutropenia (50%), infection (13%), arthralgias/myalgias (3%), skin (8%), lung (3%), and allergic reaction (3%), with no Grade 5 toxicity. The response was assessed radiographically and by panendoscopy. At the primary site, 11 patients (28%) had a complete response, 24 (62%) had a partial response, and 4 (10%) had stable disease. Of those with lymph node involvement, 10 (31%) had a complete response, 12 (38%) a partial response, 9 (28%) had stable disease, and 1 (3%) had progressive disease. The overall response rate was 82%.
Low-dose fractionated RT combined with paclitaxel and carboplatin is effective in SCCHN and has a similar toxicity profile to chemotherapy alone. This novel approach provided a response rate of 90% at the primary site and a nodal response rate of 69%. Additional scientific investigation of this new treatment paradigm is warranted.
目前针对局部晚期头颈部鳞状细胞癌(SCCHN)的治疗方法能使50%的患者获得长期缓解。低剂量放疗(<100 cGy)通过超辐射敏感性现象在体外诱导增强的细胞杀伤作用,但尚未应用于临床。基于化疗与低剂量分割放疗之间已证实的协同作用,设计了一种新辅助治疗方案,使用低剂量分割放疗作为局部晚期SCCHN的化疗增效剂。
40例局部晚期SCCHN患者接受紫杉醇(225 mg/m²)、卡铂(曲线下面积为6)以及四次80 cGy的放疗(第1天和第2天各两次)。该疗程在第22天和第23天重复。
40例入组患者中,39例可评估。3级或更严重的毒性包括中性粒细胞减少(50%)、感染(13%)、关节痛/肌痛(3%)、皮肤(8%)、肺部(3%)和过敏反应(3%),无5级毒性。通过影像学和全内镜检查评估反应。在原发部位,11例患者(28%)完全缓解,24例(62%)部分缓解,4例(10%)病情稳定。在有淋巴结受累的患者中,10例(31%)完全缓解,12例(38%)部分缓解,9例(28%)病情稳定,1例(3%)病情进展。总缓解率为82%。
低剂量分割放疗联合紫杉醇和卡铂对SCCHN有效,且毒性特征与单纯化疗相似。这种新方法在原发部位的缓解率为90%,淋巴结缓解率为69%。有必要对这种新的治疗模式进行进一步的科学研究。