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

在基础研究中，在体外研究放射同时联合5-氟尿嘧啶（5-FU）、顺铂（CDDP）或两种药物对FM3A细胞存活的影响。用药物和/或放射治疗后的细胞存活通过菌落形成试验进行评估。长时间暴露于5-FU和CDDP比脉冲暴露更有效地杀死细胞。辐射与这些药物24小时连续暴露的组合导致放射致敏，而CDDP与辐射联合1小时脉冲暴露没有显示出增强的细胞杀伤。此外，5-FU和CDDP与辐射同时持续暴露导致超加性放射增敏效应。虽然这种超加性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。在临床研究中，对28例不能手术的食管鳞状细胞癌患者进行同步放化疗，包括常规外置放疗和按比例低剂量连续输注5-FU （300mg/m^2/天）。急性毒副反应包括吞咽痛（39%）、厌食（39%）、恶心（32%）和腹泻（14%），通常由药物控制。计划治疗在25/28（89%）完成。采用该方案治疗的局限性食管癌患者（n=24）与单纯采用常规放疗的患者（n=24）进行多因素分析，结果显示该方案对局部无复发率有显著影响。生存率的多变量分析也显示了治疗的显著性。综上所述，联合治疗在临床上是可行的，可以有效提高食管癌的局部控制率和生存率。

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 .