BASIC AND CLINICAL RESEARCH ON THE CONCURRENT CHEMORADIOTHERAPY WITH PROTRACTED LOW DOSE CONTINUOUS INFUSION OF 5-FLUOROURACIL

在基础研究中，在体外研究了放射同时与5-氟尿嘧啶（5-FU）、顺铂（CDDP）或两种药物联合对FM 3A细胞存活的影响。通过集落形成试验评估药物和/或辐射处理后的细胞存活率。5-FU和CDDP的长期暴露在杀死细胞方面比脉冲暴露有效得多。辐射与24小时连续暴露的这些药物的组合导致放射增敏，而1小时脉冲暴露的CDDP与辐射结合并没有显示出增强的细胞杀伤。此外，5-FU和CDDP联合放射的同时连续暴露导致超累加放射增敏作用。尽管这种超累加放射增敏的机制尚不清楚，但CDDP对细胞内5-FU代谢的生化调节可能与此有关。对28例不能手术切除的食管鳞癌患者采用常规外照射加5-氟尿嘧啶（5-FU）持续静脉滴注同步放化疗（300 mg/m^2/天）。该联合治疗的急性毒性包括吞咽疼痛（39%）、厌食（39%）、恶心（32%）和腹泻（14%），通常通过药物控制。25/28例（89%）完成了计划的治疗。采用多因素分析方法对24例局部食管癌患者进行了多因素分析，结果显示，采用该方案治疗（n=24）或单纯常规放射治疗（n=24）的局部无复发率有显著性差异。对生存率的多变量分析也表明治疗是有意义的。结论：联合治疗在临床上是可行的，并被认为是有效的，以提高局部控制率和生存的食管癌。

In the basic study, the effects of radiation simultaneously combined with 5-fluorouracil (5-FU), cisplatin (CDDP), or both drugs on FM3A cell survival were investigated in vitro. Cell survival following treatment with the drugs and/or radiation was evaluated bycolony formation assays. Prolonged exposure of 5-FU as well as CDDP were far more effective in killing cells than pulse exposure. The combination of radiation with 24-hr continuous exposure of these drugs resulted in radiosensitization, while 1-hr pulse exposure of CDDP combined with radiation did not show an enhanced cell killing. In addition, concurrent continuous exposure of 5-FU and CDDP combined with radiation resulted in a supra-additive radiosensitizing effect. Although the mechanism of this supra-additive radiosensitization is unknown, the biochemical modulation of CDDP on the intracellular 5-FU metabolism may be related .In the clinical study, 28 patients with inoperable esophageal squamous cell carcinoma were treated with the concurrent chemoradiotherapy consisting of conventional external radiotherapy and protoracted low dose continuous infusion of 5-FU (300mg/m^2/day) .The acute toxicity of this combined treatment consisted of swallowing pain (39%), anorexia (39%), nausea (32%) and diarrhea (14%), which were usually controlled by medication . The planned treatment was accomplished in 25/28 (89%) . Patients with localized esophageal carcinoma who were treated with this regimen (n=24) or the conventional radiotherapy alone (n=24) were analyzed by the multivariate method, which revealed the treatment to be significant in the local relapse-free rate . The multivariate analysis on survival also demonstrated the treatment to be significant . In conclusion, the combined treatment was clinically feasible and was considered to be effective in increasing the local control rate and survival of esophageal cancer .