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

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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 .