Overgaard J, Hansen H S, Overgaard M, Bastholt L, Berthelsen A, Specht L, Lindeløv B, Jørgensen K
Department of Experimental Clinical Oncology, Danish Cancer Society, Aarhus University Hospital, Aarhus C, Denmark.
Radiother Oncol. 1998 Feb;46(2):135-46. doi: 10.1016/s0167-8140(97)00220-x.
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.
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.
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.
Nimorazole significantly improves the effect of radiotherapeutic management of supraglottic and pharynx tumors and can be given without major side-effects.
一项多中心随机均衡双盲试验，旨在评估尼莫唑作为低氧放疗增敏剂联合声门上喉癌和咽癌根治性放疗的疗效及耐受性。
1986年1月至1990年9月期间，422例（414例符合条件）咽癌和声门上喉癌患者被双盲随机分组，接受低氧细胞放疗增敏剂尼莫唑或安慰剂，联合常规根治性放疗（62 - 68 Gy，每次2 Gy，每周5次）。中位观察时间为112个月。
单因素分析显示，结局（5年精算局部区域肿瘤控制率）与T分期（T1 - T2为48%，T3 - T4为36%，P = 0.0008）、颈部淋巴结（N - 为53%，N + 为33%）、放疗前血红蛋白（Hb）浓度（高为46%，低为37%，P = 0.02）以及性别（女性为51%，男性为38%，P = 0.03）显著相关。总体而言，尼莫唑组的局部区域控制率显著优于安慰剂组（49%对33%，P = 0.002）。在最终局部区域控制（包括手术挽救）和癌症相关死亡的终点方面，也观察到尼莫唑有类似的显著益处（52%对41%，P = 0.002）。在总生存率方面也发现了这种趋势，但程度较轻，无统计学意义（26%对16%，10年精算值，P = 0.32）。Cox多因素回归分析显示，局部区域控制最重要的预后参数为阳性颈部淋巴结（相对风险1.84（1.38 - 2.45））、T3 - T4肿瘤（相对风险1.65（1.25 - 2.17））和尼莫唑（相对风险0.69（0.52 - 0.90））。相同参数也与死于癌症的概率显著相关。放疗依从性良好，98%的患者接受了计划剂量。10%的患者出现了晚期放疗相关并发症，与是否接受尼莫唑治疗无关。药物相关副作用轻微且可耐受，最常见的并发症为短暂性恶心和呕吐。
尼莫唑显著提高了声门上和咽肿瘤放疗的疗效，且给药时无严重副作用。
