Milas Luka, Fang Fu-Min, Mason Kathy A, Valdecanas David, Hunter Nancy, Koto Masashi, Ang K Kian
Department of Experimental Radiation Oncology, The University of Texas M D Anderson Cancer Center, Houston, TX 77030-4009, USA.
Int J Radiat Oncol Biol Phys. 2007 Feb 1;67(2):568-72. doi: 10.1016/j.ijrobp.2006.09.044.
C225 strongly enhances tumor radioresponse when given concurrently with radiotherapy. We investigated whether additional therapeutic benefit could be achieved by continuing maintenance treatment with C225 after the completion of fractionated radiotherapy.
A431 xenografts were treated with local irradiation or combined with C225 by two different schedules: (1) 6 h before the first dose of irradiation and at 3-day intervals for a total of 3 doses during the 7-day fractionated radiotherapy, or (2) 6 doses of C225 given both during radiotherapy and continuing for 3 additional doses after radiotherapy. Tumor cure was assessed by the radiation dose yielding local tumor control in 50% of animals (TCD50), and time to recurrence was also determined.
Both treatment schedules increased radiocurability as evidenced by reductions in TCD50, but the effect was greater when C225 was given both during and after radiotherapy. C225 reduced the TCD50 of 83.1 (73.2-124.8) Gy by radiation only to 46.2 (39.1-57.5) Gy when given during radiotherapy and to 30.8 (22.2-38.0) Gy when given during and after radiotherapy. Dose modification factors were 1.8 when C225 was given during radiotherapy and 2.7 when given both during and after radiotherapy. C225 was also effective in delaying the onset of tumor recurrences, and was more effective when given as both concurrent and maintenance therapy.
Data showed that C225 strongly enhanced the curative effect of fractionated radiation, and its effect was greater if administration was extended beyond the end of radiotherapy. This important finding may influence future designs of clinical trials combining anti-EGFR (anti-epidermal growth factor receptor) agents with radiotherapy.
C225与放疗同时使用时可显著增强肿瘤的放射反应。我们研究了在分次放疗完成后继续用C225进行维持治疗是否能获得额外的治疗益处。
A431异种移植瘤采用两种不同方案进行局部照射或联合C225治疗：（1）在第一次照射剂量前6小时给予，之后每3天给药一次，在7天分次放疗期间共给药3次；或（2）在放疗期间给予6次C225，并在放疗后继续给予3次。通过使50%的动物实现局部肿瘤控制的放射剂量（TCD50）评估肿瘤治愈情况，并确定复发时间。
两种治疗方案均提高了放射治愈率，表现为TCD50降低，但当C225在放疗期间及放疗后均给药时效果更佳。仅放疗时，C225将TCD50从83.1（73.2 - 124.8）Gy降至放疗期间给药时的46.2（39.1 - 57.5）Gy，以及放疗期间及放疗后均给药时的30.8（22.2 - 38.0）Gy。放疗期间给予C225时剂量修正因子为1.8，放疗期间及放疗后均给药时为2.7。C225在延迟肿瘤复发方面也有效，同时进行和维持治疗时效果更佳。
数据表明C225可显著增强分次放疗的疗效，若给药时间延长至放疗结束后，其效果更佳。这一重要发现可能会影响未来将抗EGFR（抗表皮生长因子受体）药物与放疗联合的临床试验设计。
