CCC Tübingen, Centre for Genitourinary Oncology, Department of Radiation Oncology, University of Tübingen, Tübingen, Germany.
Radiat Oncol. 2006 Apr 10;1:9. doi: 10.1186/1748-717X-1-9.
Current approaches for the improvement of bNED for prostate cancer patients treated with radiotherapy mainly focus on dose escalation. However molecularly targeted approaches may also turn out to be of value. In this regard cyclooxygenase (COX)-2 inhibitors have been shown to exert some anti-tumour activities in human prostate cancer in vivo and in vitro. Although in vitro data indicated that the combination of COX-2 inhibition and radiation was not associated with an increased toxicity, we performed a phase I trial using high dose celecoxib together with percutaneous radiation therapy.
In order to rule out any increases of more than 20% incidence for a given side effect level 22 patients were included in the trial. Celecoxib was given 400 mg twice daily with onset of the radiation treatment. Risk adapted radiation doses were between 70 and 74 Gy standard fractionation. RTOG based gastrointestinal (GI) and genitourinary (GU) acute toxicity scoring was performed weekly during radiation therapy, at six weeks after therapy and three month after completing radiation treatment.
Generally no major increase in the level and incidence of side effects potentially caused by the combined treatment was observed. In two cases a generalised skin rash occurred which immediately resolved upon discontinuation of the drug. No grade 3 and 4 toxicity was seen. Maximal GI toxicity grade 1 and 2 was observed in 85% and 10%, respectively. In terms of GU toxicity 80% of the patients experienced a grade 1 toxicity and 10 % had grade 2 symptoms.
The combination of irradiation to the prostate with concurrent high dose celecoxib was not associated with an increased level of side effects.
目前，提高接受放疗的前列腺癌患者无病生存率（bNED）的方法主要集中在提高剂量上。然而，分子靶向治疗方法也可能具有价值。在这方面，环氧化酶（COX）-2 抑制剂已被证明在体内和体外对人前列腺癌具有一定的抗肿瘤活性。尽管体外数据表明 COX-2 抑制与放射联合应用不会增加毒性，但我们进行了一项使用高剂量塞来昔布联合经皮放射治疗的 I 期试验。
为了排除任何给定副作用水平发生率增加超过 20%的情况，该试验纳入了 22 名患者。塞来昔布在放射治疗开始时每天两次口服 400mg。适应风险的放射剂量在 70 到 74Gy 标准分割之间。在放射治疗期间每周、治疗结束后 6 周和完成放射治疗后 3 个月进行 RTOG 基于胃肠道（GI）和泌尿生殖系统（GU）急性毒性评分。
一般来说，未观察到联合治疗潜在引起的副作用水平和发生率的显著增加。有两例出现全身性皮疹，停药后立即消退。未观察到 3 级和 4 级毒性。GI 毒性最大为 1 级和 2 级，分别为 85%和 10%。GU 毒性方面，80%的患者出现 1 级毒性，10%的患者出现 2 级症状。
前列腺放射治疗联合高剂量塞来昔布不会增加副作用水平。
