时辰化疗在结肠癌肝转移中的应用

THE STUDY OF CHRONOCHEMOTHERAPY IN LIVER METASTASES FROM COLORECTAL CANCER

目的目前,大量的临床及实验室资料证实,肿瘤患者的化疗效果受给药时间的影响。经过多年的研究,如今大部分的化疗药已经具备了部分时辰化疗方面的基础和临床研究数据。自1985年Hrushesky率先运用阿霉素和DDP进行卵巢癌时辰治疗以来,恶性肿瘤时辰化疗的基础与临床研究成为一个非常活跃的领域。目前,国内外相关资料显示时辰化疗已广泛应用于各种恶性肿瘤的化学治疗中,如胃癌、肠癌、鼻咽癌、肺癌、恶性淋巴瘤、肾癌、乳腺癌等恶性肿瘤,并且取得了可喜效果,其主要优势是时辰化疗的疗效显著高于常规化疗,且其毒副作用显著低于常规化疗,达到了减毒增效的目的 ,能改善患者生存质量,延长生存期。结肠癌肝转移方面尚未见大宗文献报道。本课题研究通过时辰化疗与常规化疗在结肠癌肝转移中的临床应用,以观察两种治疗方式的近期疗效及毒副作用。方法两组病例肝转移灶均初始无手术切除指征,行肝动脉置化疗泵术后,经肝动脉灌注化疗。所用药物及剂量均相同。L-OHP 50 mg,第1~3天,5-FU,第1~5天。CF 0.2,全身静脉给药,第1~5天。常规化疗组用药时间安排在正常上班的8 am^5 pm,时辰化疗组采用法国AGUETTANT公司提供的M elod ie多通道编程输液泵,以正弦曲线形式,5-FU与CF从10 pm到10 am连续12 h给药,4 am达给药高峰;L-OHP则从10 am到10pm连续给药,4 pm达给药高峰。患者化疗前均行CT检查,化疗3周期后复查CT,评价化疗的毒副反应及疗效。结果时辰化疗组总有效率为68.0%,常规辅助化疗组为29.1%,时辰化疗组近期客观疗效明显优于常规组,差异具有显著性(χ2=7.389,P<0.01)。化疗后继行手术切除的患者,时辰化疗组为44%,常规辅助化疗组为12%,差异具有显著性(χ2=5.9535,P<0.05)。毒副反应方面,时辰化疗组发生静脉炎、末梢神经炎明显少于常规组病人,发生率分别为4%、28%和70.8%、62.5%(P<0.05),其它毒副反应两组间比较差异无统计学意义。结论 1时辰化疗组在治疗结肠癌肝转移中较常规化疗组能显著提高疗效及手术切除率。2时辰化疗组毒副反应较常规化疗组显著减轻,耐受增强。

Objective at present,most of the data form clinical and laboratory study indicated that the effect of chemotherapy is influenced by the timing of administration.Through many year′s research,most of chemotherapy medicines have owned basic and clinic experiment data.After Hrushesky has taken adriamycin and cisplatin in ovarian cancer in 1985,the study of chronochemotherapy in malignant tumor had been become the Warm spots in chemotherapy.At present,the chronochemotherapy have been used in all kinds of malignant tumors generally,for example,gastric cancer,rectal cancer,nasopharyngeal carcinoma,lung cancer,malignant lymphoma,renal carcinoma,breast cancer and so on.Based on the circadian rhythms of metabolism,selecting the suitable administration,we can obtain the highest performance and the lowest toxicity,so as to improve the survival quality,and prolong survival time,through the study of chronochemotherapy and conventional chemotherapy in the treatment of liver metastases from colorectal cancer,we aim to evaluate the short term toxic side effects and efficacy.Methods L-OHP was given by sinusoid form 10 am to 10 pm with vertex at 4 pm with fluorouracil from 10 am to 10 pm with vertex at 4am in group chronochemotherapy.In group routine the same doses of LOHP and fluorouracil were given in daily working time from 8am to 5pm by the routine infusion method.The short term toxic side effects and efficacy were evaluated after completing two cycles of chemotherapy and the followed by radical hysterectomy or radiotherapy.Results total response rate was higher in group chronochemotherapy than that in group routine.Grade 3 or 4 toxic side effects were mainly the decrease of white blood corpuscles which were remarkably lower in group chronochemotherapy that in group routine（P0.05）,and there were no statistical differences in the other toxic sides effects.Conclusion The short term efficacy is apparently higher in chronotherapy group than in that the routine group B.however,there is no difference in the short term toxic side effects between these two groups.The chronochemotherapy infusion is useful in liver metastases from colorectal cancer.