Willner J, Flentje M
Klinik und Poliklinik für Strahlentherapie, Universität Würzburg.
Strahlenther Onkol. 1999 Oct;175 Suppl 3:14-9. doi: 10.1007/BF03215922.
In the last few years platin-based radiochemotherapy has become standard treatment for patients with advanced, surgically unresectable non-small-cell lung cancer (NSCLC). More recently new chemotherapeutic agents have shown superior activity. Among them paclitaxel (Taxol) is one of the most extensively investigated.
Despite of promising initial results, locally uncontrolled tumor and distant metastases continue to be the most serious problem of this disease. Improvement of local control can be achieved by escalating radiation dose, by shortening of treatment time with accelerated fractionation or by additional use of radiosensitizing agents. Concerning local control a tumor volume-dose relationship has been described. Three-dimensional conformal treatment planning eventually with intensity modulated fields, combined with biological TCP/NTCP calculation models allows risk-adapted escalation and intensification of irradiation.
A radiosensitizing effect of Taxol by means of G2/M block has been reported. However, radiobiological data are contradictory and suggest a radiosensitizing effect even without cell-cycle arrest. For simultaneous paclitaxel and 60 Gy normally fractionated radiotherapy several prospective dose escalation studies have confirmed a maximum weekly Taxol dose of 60 mg/m2. Changes in paclitaxel application (e.g. daily, twice weekly or biweekly) or in radiotherapy fractionation require a corresponding adaption of Taxol dose. Dose limiting toxicity of this simultaneous treatment is esophagitis. With respect to the high rate of distant metastases sequential application of combined chemotherapeutic regimens (e.g. Taxol 200 mg/m2/Carboplat AUC 6) is generally recommended.
在过去几年中,铂类放化疗已成为晚期、手术无法切除的非小细胞肺癌(NSCLC)患者的标准治疗方法。最近,新的化疗药物显示出更高的活性。其中,紫杉醇(泰素)是研究最为广泛的药物之一。
尽管初期结果令人鼓舞,但局部肿瘤未得到控制和远处转移仍然是该疾病最严重的问题。提高局部控制率可以通过增加放射剂量、采用加速分割缩短治疗时间或额外使用放射增敏剂来实现。关于局部控制,已经描述了肿瘤体积与剂量的关系。三维适形治疗计划最终采用调强野,并结合生物学肿瘤控制概率(TCP)/正常组织并发症概率(NTCP)计算模型,可实现根据风险调整放射剂量的增加和强化。
已有报道称紫杉醇通过G2/M期阻滞产生放射增敏作用。然而,放射生物学数据相互矛盾,表明即使没有细胞周期阻滞也可能存在放射增敏作用。对于同时使用紫杉醇和60 Gy常规分割放疗,多项前瞻性剂量递增研究已证实紫杉醇的最大每周剂量为60 mg/m²。紫杉醇应用方式的改变(如每日、每周两次或每两周一次)或放疗分割方式的改变需要相应调整紫杉醇剂量。这种同步治疗的剂量限制性毒性是食管炎。鉴于远处转移率较高,一般建议序贯应用联合化疗方案(如紫杉醇200 mg/m²/卡铂AUC 6)。