A randomized double-blind phase III study of nimorazole as a hypoxic radiosensitizer of primary radiotherapy in supraglottic larynx and pharynx carcinoma, results of the Danish Head and Neck Cancer Study (DAHANCA) protocol 5-85
A randomized double-blind phase III study of nimorazole as a hypoxic radiosensitizer of primary radiotherapy in supraglottic larynx and pharynx carcinoma, results of the Danish Head and Neck Cancer Study (DAHANCA) protocol 5-85
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DOI：
10.1016/s0167-8140(97)00220-x
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发表时间：
1998-02-01
影响因子：
5.7
通讯作者：
Jorgensen, K
中科院分区：
文献类型：
--
作者：
Overgaard, J;Hansen, HS;Jorgensen, K
目的：一项多中心随机平衡双盲试验，目的是评估尼莫唑作为低氧放射增敏剂联合声门上喉部和咽部浸润性癌的原发性放疗的疗效和耐受性。患者和治疗：在1986年1月至1990年9月期间，422名咽喉癌和声门上喉癌患者（414名符合条件）随机接受低氧细胞放射增敏剂尼莫唑或安慰剂，与常规初次放疗（62-68 Gy， 2 Gy /次，每周5次）相关。结果：单因素分析显示，结局（5年精算局部-区域肿瘤对照）与t分类（T1-T2 48% vs T3-T4 36%, P = 0.0008）、颈结（N - 53% vs N + 33%）、放疗前血红蛋白（Hb）浓度（高46% vs低37%，P = 0.02）和性别（女性51% vs男性38%，P = 0.03）显著相关。总体而言，尼莫唑组的局部区域控制率明显优于安慰剂组（49%对33%，P = 0.002），在最终局部区域控制终点（包括手术挽救）和癌症相关死亡（52%对41%，P = 0.002）方面，尼莫唑也有类似的显著益处，但在总生存中也发现了这种趋势，但程度较小，不显著（26%对16%，10年精算值，P = 0.32）。Cox多因素回归分析显示，淋巴结阳性（相对危险度1.84(1.38-2.45)）、T3-T4肿瘤（相对危险度1.65(1.25-2.17)）和尼莫唑（相对危险度0.69(0.52-0.90)）是局部-区域对照最重要的预后参数。放疗依从性良好，98%的患者接受了计划剂量的放疗。在10%的患者中观察到晚期放射相关发病率，无论尼莫唑治疗如何，药物相关副作用轻微且可耐受，短暂性恶心和呕吐是最常见的并发症。结论：尼莫唑能显著提高声门上及咽部肿瘤的放射治疗效果，且给药无重大副作用。(C) 1998爱思唯尔科学爱尔兰有限公司
Purpose: A multicenter randomized and balanced double-blind trial with the objective of assessing the efficacy and tolerance of nimorazole given as a hypoxic radiosensitizer in conjunction with primary radiotherapy of invasive carcinoma of the supraglottic larynx and pharynx.Patients and treatment: Between January 1986 and September 1990, 422 patients (414 eligible) with pharynx and supraglottic larynx carcinoma were double-blind randomized to receive the hypoxic cell radiosensitizer nimorazole, or placebo, in association with conventional primary radiotherapy (62-68 Gy, 2 Gy per fraction, five fractions per week). The median observation time was 112 months,Results: Univariate analysis showed that the outcome (5-year actuarial loco-regional tumor control) was significantly related to T-classification (T1-T2 48% versus T3-T4 36%, P = 0.0008), neck-nodes (N - 53% versus N + 33%), pre-irradiation hemoglobin (Hb) concentration (high 46% versus low 37%, P = 0.02) and sex (females 51% versus males 38%, P = 0.03). Overall the nimorazole group showed a significantly better loco-regional control rate than the placebo group (49 versus 33%, P = 0.002), A similar significant benefit of nimorazole was observed for the end-points of final loco-regional control (including surgical salvage) and cancer-related deaths (52 versus 41%, P = 0.002), This trend was also found in the overall survival but To a lesser, non-significant extent (26 versus 16%, 10-year actuarial values, P = 0.32). Cox multivariate regression analysis showed the most important prognostic parameters for loco-regional control to be positive neck nodes (relative risk 1.84 (1.38-2.45)), T3-T4 tumor (relative risk 1.65 (1.25-2.17)) and nimorazole (relative risk 0.69 (0.52-0.90)). The same parameters were also significantly related to the probability of dying from cancer, The compliance to radiotherapy was good and 98% of the patients received the planned dose. Late radiation-related morbidity was observed in 10% of the patients, irrespective of nimorazole treatment, Drug-related side-effects were minor and tolerable with transient nausea and vomiting being the most frequent complications.Conclusion: Nimorazole significantly improves the effect of radiotherapeutic management of supraglottic and pharynx tumors and can be given without major side-effects. (C) 1998 Elsevier Science Ireland Ltd.