Metz James M, Smith Debbie, Mick Rosemarie, Lustig Robert, Mitchell James, Cherakuri Murali, Glatstein Eli, Hahn Stephen M
Department of Radiation Oncology, University of Pennsylvania, Philadelphia 19104-4283, USA.
Clin Cancer Res. 2004 Oct 1;10(19):6411-7. doi: 10.1158/1078-0432.CCR-04-0658.
Complete alopecia is a universal complication of whole brain radiation therapy which contributes to patient anxiety over treatment. Tempol, a nitroxide radioprotector, has been shown to protect against radiation-induced alopecia in an animal model. This phase Ib study was designed to evaluate the safety and side effect profile of topical Tempol in patients with brain metastases being treated with whole brain radiotherapy.
Twelve patients with metastatic cancer to the brain were enrolled in the study between October 2000 and February 2003. Tempol (70 mg/ml concentration solution) was applied topically to the scalp 15 minutes before and washed off immediately after the completion of each of 10 fractions of whole brain radiation. Pharmacokinetic studies to evaluate the systemic absorption of Tempol were performed. Patients were assessed for toxicity before, during, and after Tempol administration. A secondary end point of the study, hair retention, was also scored.
Eleven patients were treated with topical Tempol. Adverse events that were considered possibly, probably, or definitely related to Tempol, included asymptomatic grade 2 (two patients) and grade 1 (one patient) hypoglycemia, grade 1 forehead skin redness (one patient), grade 1 dry scalp (one patient), and grade 1 tingling sensation on the scalp (one patient). Tempol was not detected in blood samples from more than 50% of the patients. Mean maximum Tempol levels for individual patients at any time point varied from 0.4 to 3.1 micromol/L. Hair retention was localized to the base of the scalp where the Tempol solution pooled after application in the first four patients on the study. Subsequently, full scalp hair retention was seen in three of final five evaluable patients after gauze had been wrapped around the head to hold the solution against the scalp.
This study demonstrates that topical application of Tempol to the scalp before whole brain radiation is safe and well tolerated. Evidence of protection against radiation-induced alopecia was observed. A phase II study that uses a gel formulation to increase the exposure of scalp to Tempol has been initiated.
全秃是全脑放射治疗的常见并发症，会加剧患者对治疗的焦虑。Tempol是一种氮氧化物辐射防护剂，已在动物模型中显示出可预防辐射诱导的脱发。这项Ib期研究旨在评估局部应用Tempol对接受全脑放疗的脑转移患者的安全性和副作用情况。
2000年10月至2003年2月期间，12例脑转移癌患者入组本研究。在每次全脑放疗的10个分次完成前15分钟，将Tempol（浓度为70mg/ml的溶液）局部涂抹于头皮，放疗结束后立即冲洗掉。进行了药代动力学研究以评估Tempol的全身吸收情况。在Tempol给药前、给药期间和给药后对患者进行毒性评估。该研究的次要终点——毛发保留情况也进行了评分。
11例患者接受了局部Tempol治疗。被认为可能、很可能或肯定与Tempol相关的不良事件包括无症状的2级（2例患者）和1级（1例患者）低血糖、1级前额皮肤发红（1例患者）、1级头皮干燥（1例患者）以及1级头皮刺痛感（1例患者）。超过50%的患者血液样本中未检测到Tempol。各患者在任何时间点的平均最大Tempol水平在0.4至3.1微摩尔/升之间。在前4例入组研究的患者中，毛发保留局限于头皮基部，即Tempol溶液涂抹后积聚的部位。随后，在最后5例可评估患者中的3例，在头部包裹纱布以使溶液紧贴头皮后，出现了全头皮毛发保留。
本研究表明，在全脑放疗前将Tempol局部应用于头皮是安全且耐受性良好的。观察到了预防辐射诱导脱发的证据。已启动一项II期研究，使用凝胶制剂以增加头皮对Tempol的暴露。
