Locally advanced head and neck cancer treated with accelerated radiotherapy, the hypoxic modifier nimorazole and weekly cisplatin. Results from the DAHANCA 18 phase II study
Locally advanced head and neck cancer treated with accelerated radiotherapy, the hypoxic modifier nimorazole and weekly cisplatin. Results from the DAHANCA 18 phase II study
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DOI：
10.3109/0284186x.2014.992547
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发表时间：
2015-01-01
期刊：
影响因子：
3.1
通讯作者：
Overgaard, Jens
中科院分区：
文献类型：
--
作者：
Bentzen, Jens;Toustrup, Kasper;Overgaard, Jens
目的/目标。一项II期临床试验，评估加速放疗、低氧调节剂尼莫拉唑和每周顺铂治疗局部晚期头颈部鳞状细胞癌（HNSCC）的可行性和结果。2007年1月至2010年12月期间，共纳入227例喉、口咽、下咽或口腔III期或IV期HNSCC患者。放疗剂量66-68戈伊，分2次戈伊，每周6次。在每次分次前口服1200 mg/m2剂量的低氧放射增敏剂尼莫拉唑。伴随顺铂（40 mg/m2）静脉注射，每周一次，最多6个周期。根据局部区域肿瘤控制（LRC）、无事件生存期（EFS）和总生存期（OS）评价结局数据。基于DAHANCA常规登记对发病率数据进行评价。采用免疫组化p16染色法检测人乳头瘤病毒（HPV）感染情况。包括178名（78%）男性和49名（22%）女性，中位年龄为57岁。除5名患者外，所有患者均按规定接受RT。164名患者（72%）接受了至少5个系列的顺铂治疗，149名患者（66%）接受了全剂量的尼莫拉唑治疗。五年精算LRC、EFS和OS率分别为80%、67%和72%。不同部位的LRC发生率分别为：口咽：88%，喉：77%，下咽部72%，口腔49%。150例口咽癌中141例HPV/p16染色阳性。其中112例（79%）为p16阳性，29例（21%）为p16阴性。p16阴性口咽癌的LRC比p16阳性口咽癌差（74% vs. 91%; p = 0.02）。146例（64%）患者在治疗期间需要管饲。12个月时，这一数字降至6%。在该局部晚期HNSCC患者队列中，治疗是可耐受的。急性和晚期毒性与放化疗的类似研究相当，结局上级于文献报道的数据。这有力地表明，晚期头颈癌的RT必须包括低氧修饰，加速分割作为放化疗，以产生最佳结果。
Purpose/Objective. A phase II clinical trial evaluating the feasibility and outcome of treating locally advanced head and neck squamous cell carcinoma (HNSCC) with accelerated radiotherapy, the hypoxic modifier nimorazole and weekly cisplatin.Material and methods. A total of 227 patients with stage III or IV HNSCC of the larynx, oropharynx, hypopharynx, or oral cavity where included between January 2007 and December 2010. The prescribed radiotherapy (RT) dose was 66-68 Gy in 2 Gy fractions, 6 F/W. The hypoxic radiosensitiser nimorazole was given orally at a dose of 1200 mg/m(2) before each fraction. Concomitant cisplatin (40 mg/m(2)) i.v. was given once a week for a maximum of six cycles. Outcome data were evaluated in terms of loco-regional tumour control (LRC), event-free survival (EFS) and overall survival (OS). Morbidity data were evaluated based on the DAHANCA routine registration. Human papillomavirus (HPV)-status was estimated by immunohistochemical staining of p16.Results. Included were 178 (78%) men and 49 (22%) women with a median age of 57 years. All except five patients received RT as prescribed. At least five series of cisplatin was given to 164 (72%) of the patients, and 149 patients (66%) received the full dose of nimorazole. The five-year actuarial LRC, EFS and OS rates were 80%, 67% and 72%, respectively. The LRC rates according to site were: oropharynx: 88%, larynx: 77%, hypopharynx 72% and oral cavity 49%, respectively. HPV/p16 staining was obtained in 141 of the 150 oropharyngeal cancers. Of these, 112 (79%) were p16 pos and 29 (21%) were p16 neg. LRC for the p16 neg oropharyngeal cancers was poorer than for the p16 pos (74% vs. 91%; p = 0.02). Tube feeding during treatment was necessary for 146 (64%) patients. At 12 months this number was reduced to 6%.Conclusion. The treatment was tolerable in this cohort of locally advanced HNSCC patients. Acute and late toxicity was comparable to similar studies of chemoradiotherapy, and the outcome superior to the data reported in the literature. This strongly indicates that RT of advanced head and neck cancer must include as well hypoxic modification, accelerated fractionation as chemoradiotherapy to yield optimal outcome.