Concurrent or sequential adjuvant letrozole and radiotherapy after conservative surgery for early-stage breast cancer (CO-HO-RT): a phase 2 randomised trial
Concurrent or sequential adjuvant letrozole and radiotherapy after conservative surgery for early-stage breast cancer (CO-HO-RT): a phase 2 randomised trial
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DOI：
10.1016/s1470-2045(10)70013-9
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发表时间：
2010-03-01
期刊：
影响因子：
51.1
通讯作者：
Ozsahin, Mahmut
中科院分区：
文献类型：
--
作者：
Azria, David;Belkacemi, Yazid;Ozsahin, Mahmut
来曲唑对乳腺癌细胞的体外放射致敏作用。在临床环境中，没有关于来曲唑和放疗联合使用的数据。我们评估了同步和顺序放疗以及来曲唑在辅助治疗中的作用。该2期随机试验于2005年1月12日至2007年2月21日在法国的两个中心和瑞士的一个中心进行。150名绝经后早期乳腺癌妇女在保存手术后被随机分配到同步放疗和来曲唑组（n=75）或序贯放疗和来曲唑组（n=75）。随机化采用最小化技术，按研究中心、化疗（是或否）、辐射增强（是或否）和辐射诱导淋巴细胞凋亡值（16%）分层。整个乳房在5周内被照射到总剂量为50戈瑞的25个部分。在锁骨上和乳腺内淋巴结照射的情况下，剂量为44-50 Gy。来曲唑每日口服一次，剂量为2.5 mg，持续5年（伴随组放疗前3周开始，序贯组放疗后3周开始）。主要终点是急性（放射治疗期间和6周内）和晚期（2年内）放射引起的2级或更严重的皮肤毒性作用的发生。分析的目的是治疗。本研究已在ClinicalTrials.gov注册，编号NCT00208273。结果除同期组中1例患者在任何治疗前撤回同意外，所有患者均进行了分析。在放疗期间和放疗后的前12周内，同时组和顺序组分别有31例患者出现2级或更严重的皮肤相关毒性。最常见的皮肤相关不良事件是皮炎：同时组中有4名患者和顺序组中有6名患者在放疗期间发生了3级急性皮肤皮炎。在中位随访26个月（范围3-40）时，每组中有2例患者出现2级或更严重的晚期效应（均为辐射诱发的皮下纤维化）。来曲唑可以在手术后不久安全使用，并与放疗同时使用。需要长期随访来调查心脏副作用和癌症特异性结局。
Background Letrozole radiosensitises breast cancer cells in vitro. In clinical settings, no data exist for the combination of letrozole and radiotherapy. We assessed concurrent and sequential radiotherapy and letrozole in the adjuvant setting.Methods This phase 2 randomised trial was undertaken in two centres in France and one in Switzerland between Jan 12, 2005, and Feb 21, 2007. 150 postmenopausal women with early-stage breast cancer were randomly assigned after conserving surgery to either concurrent radiotherapy and letrozole (n=75) or sequential radiotherapy and letrozole (n=75). Randomisation was open label with a minimisation technique, stratified by investigational centres, chemotherapy (yes vs no), radiation boost (yes vs no), and value of radiation-induced lymphocyte apoptosis (16%). Whole breast was irradiated to a total dose of 50 Gy in 25 fractions over 5 weeks. In the case of supraclavicular and internal mammary node irradiation, the dose was 44-50 Gy. Letrozole was administered orally once daily at a dose of 2.5 mg for 5 years (beginning 3 weeks pre-radiotherapy in the concomitant group, and 3 weeks post-radiotherapy in the sequential group). The primary endpoint was the occurrence of acute (during and within 6 weeks of radiotherapy) and late (within 2 years) radiation-induced grade 2 or worse toxic effects of the skin. Analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00208273.Findings All patients were analysed apart from one in the concurrent group who withdrew consent before any treatment. During radiotherapy and within the first 12 weeks after radiotherapy, 31 patients in the concurrent group and 31 in the sequential group had any grade 2 or worse skin-related toxicity. The most common skin-related adverse event was dermatitis: four patients in the concurrent group and six in the sequential group had grade 3 acute skin dermatitis during radiotherapy. At a median follow-up of 26 months (range 3-40), two patients in each group had grade 2 or worse late effects (both radiation-induced subcutaneous fibrosis).Interpretation Letrozole can be safely delivered shortly after surgery and concomitantly with radiotherapy. Long-term follow-up is needed to investigate cardiac side-effects and cancer-specific outcomes.