Azria David, Zouhair Abderrahim, Serre Antoine, Lemanski Claire, Schneider Maurice, Ozsahin Mahmut, Dubois Jean-Bernard, Lartigau Eric
Département d'Oncologie-Radiothérapie, EMI0227, CRLC Val d'Aurelle-Paul Lamarque, Rue Croix Verte, 34298 Montpellier Cedex.
Bull Cancer. 2005 May 1;92(5):445-51.
Anemia is very common in head and neck cancer patients, and seems to be correlated with intratumoral hypoxia. Anemia is one of the main prognostic factors of locoregional recurrence and, in some studies, of poor survival. Blood transfusions and human recombinant erythropoietin (rHuEPO) are the two main methods used in clinical practice to correct hemoglobin level during curative treatment. Blood transfusions were rarely evaluated, and did not influence locoregional control of patients treated with radiotherapy with or without chemotherapy. Retrospective studies evaluating combined treatment of rHuEPO and radiotherapy reported positive impact on locoregional recurrence and actuarial survival. Since the end of 2003, this approach is a matter for debate after the negative results of a prospective randomized study on progression-free survival concerning head and neck cancer patients treated with definitive or postoperative external radiotherapy with or without rHuEPO. Although many biases were reported against this publication, several questions are to be answered in the near future. Among them, erythropoietin receptor expression and activation on tumour cell seem to be the more appropriate explanation of these negative results. In October 2004, preliminary results of the RTOG 99-03 study have been presented at the Astro annual meeting in Atlanta. This prospective randomized trial was designed to determine if concurrent rHuEPO administration (40,000 units) with radiotherapy (with or without chemotherapy) could improve locoregional control in non-operative head and neck cancers. In the rHuEPO arm, haemoglobin level was significantly increased compared with control arm. However, the addition of concurrent rHuEPO to definitive radiotherapy did not improve locoregional control or survival for mildly/moderately anemic patients with head and neck squamous cell carcinoma. Future clinical trials using biological markers are thus imperative to target which patients could benefit from these molecules.
贫血在头颈癌患者中非常常见，且似乎与肿瘤内缺氧相关。贫血是局部区域复发的主要预后因素之一，在一些研究中也是生存预后不良的因素。输血和人重组促红细胞生成素（rHuEPO）是临床实践中用于在根治性治疗期间纠正血红蛋白水平的两种主要方法。输血很少被评估，并且对接受放疗（无论是否联合化疗）的患者的局部区域控制没有影响。评估rHuEPO与放疗联合治疗的回顾性研究报告了对局部区域复发和精算生存率有积极影响。自2003年底以来，在一项关于接受根治性或术后体外放疗（无论是否使用rHuEPO）的头颈癌患者无进展生存期的前瞻性随机研究得出阴性结果后，这种方法一直存在争议。尽管针对该出版物报道了许多偏差，但在不久的将来仍有几个问题需要解答。其中，促红细胞生成素受体在肿瘤细胞上的表达和激活似乎是对这些阴性结果更合适的解释。2004年10月，RTOG 99 - 03研究的初步结果在亚特兰大的Astro年会上公布。这项前瞻性随机试验旨在确定在放疗（无论是否联合化疗）的同时给予rHuEPO（40,000单位）是否能改善不可手术的头颈癌的局部区域控制。在rHuEPO组中，与对照组相比血红蛋白水平显著升高。然而，对于轻度/中度贫血的头颈鳞状细胞癌患者，在根治性放疗中同时添加rHuEPO并未改善局部区域控制或生存率。因此，未来使用生物标志物的临床试验势在必行，以确定哪些患者可以从这些分子中获益。
