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

5-氟尿嘧啶长期小剂量持续输注同步放化疗的基础与临床研究

• 批准号: 05454301
• 负责人: SAKAI Kunio
• 金额: $ 3.01万
• 依托单位: NIIGATA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05454301/
• 关键词: RADIOSENSITIZATION; RADIOTHERAPY; CHEMOTHERAPY; 5-FLUOROURACIL (5-FU); CISPLATIN (CDDP); ESOPHAGUS; CANCER

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 .

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。辐射与这些药物24小时连续暴露的组合导致放射增敏，而CDDP与辐射组合1小时脉冲暴露并未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急性毒性反应主要为吞咽痛（39%）、食欲减退（39%）、恶心（32%）、腹泻（14%），一般经药物治疗后可控制。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。

项目成果

SUEYAMA,H.et al.: "CONCOMITANT RADIOTHERAPY AND CHEMOTHERAPY WITH PROTRACTED LOW DOSE CONTINUOUS INFUSION OF 5-FLUOROURACIL AND CISPLATIN" JPN J CANCER CHEMOTHER. 21. 2839-2841 (1994)

SUEYAMA,H.et al.：“5-氟尿嘧啶和顺铂的长期低剂量连续输注的同步放射治疗和化疗”JPN J CANCER CHEMOTHER。

FUJITA,S.et al.: "COMBINED EFFECT OF RADIATION AND 5-FLUOROURACIL ON FM3A MOUSE MAMMARY ADENOCARCINOMA CELLS" BULL COLL BIOMED TECHNOL NIIGATA UNIV. 5. 265-269 (1995)

FUJITA,S.et al.：“辐射和 5-氟尿嘧啶对 FM3A 小鼠乳腺腺癌细胞的组合效应”BULL COLL BIOMED TECHNOL NIIGATA UNIV。

酒井 邦夫,他: "5-FU少量持続静注と放射線の同時併用療法に関する基礎的,臨床的研究" Innervision. 9(予定). (1994)

Kunio Sakai 等人：“5-FU 低容量连续静脉注射和放射同时联合治疗的基础和临床研究”Innervision 9（计划）。

末山 博男,他: "進行食道癌に対する5fluorouracil少量持続静注およびCisplatin静注と放射線の同時併用の試み" 癌と化学療法. 21. 2839-2841 (1994)

Hiroo Sueyama 等人：“同时小容量连续静脉注射 5 氟尿嘧啶和静脉顺铂注射以及放射治疗晚期食管癌的试验”《癌症与化疗》21. 2839-2841 (1994)。

HIGUCHI,S.et al.: "RADIOSENSITIZATION OF FM3A CELLS BY 5-FLUOROURACIL PLUS CISPLATIN" ACTA MEDICA ET BIOLOGICA. (IN PRINTING).

Higuchi,S.et al.：“5-氟尿嘧啶加顺铂对 FM3A 细胞的放射增敏”医学与生物学学报。