ARCON:: accelerated radiotherapy with carbogen and nicotinamide in non small cell lung cancer:: a phase I/II study by the EORTC
ARCON:: accelerated radiotherapy with carbogen and nicotinamide in non small cell lung cancer:: a phase I/II study by the EORTC
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DOI：
10.1016/s0167-8140(99)00106-1
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发表时间：
1999-08-01
影响因子：
5.7
通讯作者：
Piérart, M
中科院分区：
文献类型：
--
作者：
Bernier, J;Denekamp, J;Piérart, M
背景：非小细胞肺癌（NSCLC）是一种快速增殖的肿瘤，其特点是存在广泛的缺氧成分，特别是在患有晚期局部疾病的患者中。先前的研究表明，急性（灌注限制）缺氧对这些肿瘤的放射治疗结果产生有害影响。目的：这项试点研究旨在确定 ARCON 方案在局部晚期 IIIA 或 B 期 NSCLC 肿瘤患者中可实现的可行性和肿瘤反应率。方法，I/II 期研究包括三个步骤：加速分割 (AF) 联合卡波金（10 名可分析患者）、AF 与每日给药相结合烟酰胺 (n = 11) 和含有碳和烟酰胺的 AF (n = 14)。放射治疗基于每次分次的较大日剂量（4 周内 2.75 Gy 至 55 Gy）。烟酰胺剂量为每名患者每个治疗日6 g，放疗前和放疗期间吸入卡波金5 min。结果：放疗期间3级+急性毒性发生率不超过10%，无论是肺实质还是纵隔。在三个研究步骤中，局部区域放射诱导毒性没有发现显着差异。尽管相似比例的患者在所有步骤中均表现出 2 级或 3 级呕吐，但在进入两个含烟酰胺步骤 10 的 25 名患者中 (40%) 出现了 2 级或更严重的反应，这显着降低了他们的生活质量。三个步骤之间的肿瘤清除率没有显着差异。第 1、2 和 3 步中，2 个月时的客观反应百分比分别为 60%、54% 和 57%。 结论：该 ARCON 方案的可行性，在 4 周内每次分次使用 2.75 Gy 剂量，在与放疗相关的副作用方面效果良好，但未来似乎有必要减少烟酰胺的剂量，以减少恶心和呕吐的发生率。三个研究步骤之间的进展时间没有显着差异。 (C) 1999 Elsevier Science Ireland Ltd. 保留所有权利。
Background: Non small cell lung cancers (NSCLC) are rapidly proliferating tumours, which are characterized by the presence of extensive hypoxic components, especially in patients with advanced loco-regional disease. Previous studies suggest a deleterious impact of acute (perfusion-limited) hypoxia on the outcome of radiotherapy for these tumours.Aim: This pilot study was aimed at determining the feasibility and tumour response rates that can be achieved with an ARCON regime in patients with locally advanced, staged IIIA or B, NSCLC tumours.Methods, The phase I/II study included three steps: accelerated fractionation (AF) combined with carbogen (ten analysable patients), AF together with the daily administration of nicotinamide (n = 11) and AF with both carbon and nicotinamide (n = 14). Radiotherapy was based on a large daily dose per fraction (2.75 Gy up to 55 Gy in 4 weeks). Nicotinamide was administered at a dose of 6 g per patient per treatment day and carbogen was inhaled for 5 min before and during radiotherapy.Results: The incidence of grade 3 + acute toxicity during the irradiation did not exceed 10%, neither in the lung parenchyma nor in the mediastinum. No significant difference was found in loco-regional, radio-induced toxicity among the three study steps. Although a similar fraction of patients showed grade 2 or 3 emesis in all the steps, of the 25 patients entered in the two Nicotinamide containing steps 10 (40%) developed grade 2 or greater reactions which significantly detracted from their quality of life. There was no significant difference in tumour clearance rate among the three steps. The percentage of objective responses at 2 months was 60, 54 and 57% in steps 1, 2 and 3, respectively.Conclusion: The feasibility of this ARCON protocol, using 2.75 Gy doses per fraction over 4 weeks, is good as regards radiotherapy-related side effects but it appears necessary in future to reduce the dose of Nicotinamide to reduce the incidence of nausea and vomiting. There was no significant difference in time to progression among the three study steps. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.