Larynx preservation in pyriform sinus cancer: Preliminary results of a European organization for research and treatment of cancer phase III trial
Larynx preservation in pyriform sinus cancer: Preliminary results of a European organization for research and treatment of cancer phase III trial
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DOI：
10.1093/jnci/88.13.890
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发表时间：
1996-07-03
期刊：
影响因子：
--
通讯作者：
Sahmoud, T
中科院分区：
文献类型：
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作者：
Lefebvre, JL;Chevalier, D;Sahmoud, T
背景资料：一般来说，下咽癌的标准治疗方法是尽可能进行手术，然后进行放射治疗，从而牺牲了自然语言。在大多数患者中，手术包括切除喉部。目的：欧洲癌症研究与治疗组织（EORTC）从1990年开始进行了一项前瞻性、随机III期研究，（诱导化疗加确定性放射治疗的患者显示完全缓解或手术治疗的那些谁没有反应）与常规治疗（全喉切除术，部分咽切除术，根治性颈清扫术，术后放疗）在以前未经治疗和手术的患者与组织学证实的鳞状细胞癌的梨状窦或杓会厌褶皱，但没有其他癌症。研究方法：患者被随机分配到两个治疗组中的一个：1）立即手术，术后放疗（50-70戈伊）或2）诱导化疗（顺铂[100 mg/m2]在第1天静脉推注，然后在第1-5天输注氟尿嘧啶[1000 mg/m2/天]）。每个化疗周期后进行内镜评价。两个周期后，只有部分和完全反应者接受第三个周期。两个或三个化疗周期后完全缓解的患者随后接受放疗（70戈伊）;无反应的患者接受常规手术和术后放疗（50-70戈伊）。当患者在化疗和放疗后复发时，也进行了挽救手术。该试验旨在检验两个治疗组的等效性;即，如果在0.05的显著性水平下使用单侧假设检验，诱导化疗与立即手术相比的相对死亡风险显著小于1.43，则诱导化疗治疗将被判定为等同于立即手术。结果如下：202名患者进入试验并被随机分配;只有194名符合治疗条件（94名在立即手术组，100名在诱导化疗组）。在诱导化疗组中，97例局部疾病（原发性肿瘤）患者中有52例（54%）完全缓解，61例局部疾病（累及颈部）患者中有31例（51%）完全缓解。即刻手术组（分别为12%、19%和16%）和诱导化疗组（分别为17%、23%和13%）局部、区域和第二主要部位治疗失败的发生率大致相同。相比之下，诱导化疗组远端部位的失败率低于立即手术组（分别为25%和36%; P = 0.041）。即刻手术组的中位生存期为25个月，诱导化疗组为44个月，由于观察到的风险比为0.86（对数秩检验，P = 0.006），显著小于1.43，因此判定两种治疗等效。3年和5年的估计保留功能性喉的患者在诱导化疗臂分别为42%（95%置信区间31%-53%）和35%（95%置信区间= 22%-48%），respectively.Conclusions and Implications：喉保存而不危及生存的下咽癌患者似乎是可行的。在这些观察的基础上，EORTC现在已经接受使用诱导化疗后放疗作为其未来III期喉保存试验的新标准治疗。
Background: As a general rule, surgery whenever possible, followed by irradiation is considered to be the standard treatment for cancer of the hypopharynx, thus sacrificing natural speech. In most patients, surgery includes removal of the larynx. Purpose: A prospective, randomized phase III study was conducted by the European Organization for Research and Treatment of Cancer (EORTC) starting in 1990 to compare a larynx-preserving treatment (induction chemotherapy plus definitive, radiation therapy in patients who showed a complete response or surgery in those who did not respond) with conventional treatment (total laryngectomy with partial pharyngectomy, radical neck dissection, and postoperative irradiation) in previously untreated and operable patients with histologically proven squamous cell carcinomas of the pyriform sinus or aryepiglottic fold, but free of other cancers. Methods: Patients were randomly assigned to one of two treatment arms: 1) immediate surgery with postoperative radiotherapy (50-70 Gy) or 2) induction chemotherapy (cisplatin [100 mg/m(2)] given as a bolus intravenous injection on day 1, followed by infusion of fluorouracil [1000 mg/m(2) per day] on days 1-5). An endoscopic evaluation was performed after each cycle of chemotherapy. After two cycles, only partial and complete responders received a third cycle. Patients with a complete response after two or three cycles of chemotherapy were treated thereafter by irradiation (70 Gy); nonresponding patients underwent conventional surgery with postoperative radiation (50-70 Gy). Salvage surgery was also performed when patients relapsed after chemotherapy and irradiation. The trial was designed to test the equivalence of the two treatment arms; i.e., the induction chemotherapy treatment would be judged equivalent to immediate surgery if the relative risk of death for induction chemotherapy compared with immediate surgery was significantly less than 1.43 using a one-sided hypothesis test at the .05 level of significance. Results: Two hundred two patients entered the trial and were randomly assigned; only 194 were eligible for treatment (94 in the immediate-surgery arm and 100 in the induction-chemotherapy arm). In the induction-chemotherapy arm, complete response was seen in 52 (54%) of 97 patients with local disease (primary tumor) and in 31 (51%) of 61 patients with regional disease (involvement of the neck). Treatment failures at local, regional, and second primary sites occurred at approximately the same frequencies in the immediate-surgery arm (12%, 19%, and 16%, respectively) and in the induction-chemotherapy arm (17%, 23%, and 13%, respectively). In contrast, there were fewer failures at distant sites in the induction-chemotherapy arm than in the immediate-surgery arm (25% versus 36%, respectively; P = .041). The median duration of survival was 25 months in the immediate-surgery arm and 44 months in the induction-chemotherapy arm and, since the observed hazard ratio was 0.86 (logrank test, P = .006), which was significantly less than 1.43, the two treatments were judged to be equivalent. The 3- and 5-year estimates of retaining a functional larynx in patients treated in the induction-chemotherapy arm were 42% (95% confidence interval 31%-53%) and 35% (95% confidence interval = 22%-48%), respectively.Conclusions and Implications: Larynx preservation without jeopardizing survival appears feasible in patients with cancer of the hypopharynx. On the basis of these observations, the EORTC has now accepted the use of induction chemotherapy followed by radiation as the new standard treatment in its future phase III larynx preservation trials.