Stea B, Shaw E, Pintér T, Hackman J, Craig M, May J, Steffen R P, Suh J H
Department of Radiation Oncology, The University of Arizona Health Sciences Center, Tucson, 85724, USA.
Br J Cancer. 2006 Jun 19;94(12):1777-84. doi: 10.1038/sj.bjc.6603169.
Efaproxiral (Efaproxyn, RSR13), a synthetic allosteric modifier of haemoglobin (Hb), decreases Hb-oxygen (O(2)) binding affinity and enhances oxygenation of hypoxic tumours during radiation therapy. This analysis evaluated the Phase 3, Radiation Enhancing Allosteric Compound for Hypoxic Brain Metastases; RT-009 (REACH) study efficacy results in relation to efaproxiral exposure (efaproxiral red blood cell concentration (E-RBC) and number of doses). Recursive partitioning analysis Class I or II patients with brain metastases from solid tumours received standard whole-brain radiation therapy (3 Gy/fraction x 10 days), plus supplemental O(2) (4 l/min), either with efaproxiral (75 or 100 mg/kg daily) or without (control). Efaproxiral red blood cell concentrations were linearly extrapolated to all efaproxiral doses received. Three patient populations were analysed: (1) all eligible, (2) non-small-cell lung cancer (NSCLC) as primary cancer, and (3) breast cancer primary. Efficacy endpoints were survival and response rate. Brain metastases patients achieving sufficient E-RBC (> or =483 microg/ml) and receiving at least seven of 10 efaproxiral doses were most likely to experience survival and response benefits. Patients with breast cancer primary tumours generally achieved the target efaproxiral exposure and therefore gained greater benefit from efaproxiral treatment than NSCLC patients. This analysis defined the efaproxiral concentration-dependence in survival and response rate improvement, and provided a clearer understanding of efaproxiral dosing requirements.
依氟普胺（依氟普辛，RSR13）是一种合成的血红蛋白（Hb）变构调节剂，可降低Hb与氧（O₂）的结合亲和力，并在放射治疗期间增强缺氧肿瘤的氧合作用。本分析评估了用于缺氧性脑转移瘤的3期放射增强变构化合物；RT - 009（REACH）研究的疗效结果与依氟普胺暴露量（依氟普胺红细胞浓度（E - RBC）和给药剂量）的关系。递归划分分析来自实体瘤的I类或II类脑转移瘤患者接受标准全脑放射治疗（3 Gy/分次×10天），加用补充氧气（4 l/分钟），同时给予依氟普胺（75或100 mg/kg/天）或不给予（对照组）。依氟普胺红细胞浓度被线性外推至所接受的所有依氟普胺剂量。分析了三个患者群体：（1）所有符合条件的患者，（2）以非小细胞肺癌（NSCLC）为原发癌的患者，以及（3）原发性乳腺癌患者。疗效终点为生存率和缓解率。脑转移瘤患者达到足够的E - RBC（≥483 μg/ml）且接受10剂依氟普胺中至少7剂时最有可能获得生存和缓解益处。原发性乳腺癌患者通常达到了依氟普胺的目标暴露量，因此比NSCLC患者从依氟普胺治疗中获益更大。本分析确定了依氟普胺浓度与生存率和缓解率改善之间的相关性，并更清楚地了解了依氟普胺的给药要求。
