以奥沙利铂为基础的联合化疗方案治疗晚期胃癌的临床对照研究

目的:探讨奥沙利铂联合替加氟和亚叶酸钙方案治疗晚期胃癌的临床疗效和不良反应。方法:对60例晚期胃癌患者采用奥沙利铂联合亚叶酸钙和替加氟方案治疗(观察组),同时随机抽取既往在我院住院并采用顺铂联合表阿霉素和氟尿嘧啶(即经典ECF方案)治疗的晚期胃癌患者60例作为对照组,评价两组临床疗效和不良反应发生率差异。结果:观察组和对照组患者的临床有效率分别为63.3%(38/60)和40.0%(24/60),两组间差异有统计学意义(χ2=6.541,P=0.017);观察组患者的中位无进展生存期和中位生存期分别为7.7个月和11.6个月,对照组患者的中位无进展生存期和中位生存期分别为6.1个月和9.1个月,二者中位无进展生存期和中位生存期差异均有统计学意义(均P<0.001);观察组患者Karnofsky评分改善率明显优于对照组,二者间有统计学差异(χ2=9.855,P=0.003);观察组骨髓抑制发生率低于对照组(χ2=6.009,P=0.023),两组间其他不良反应发生率未见明显差异。结论:奥沙利铂联合替加氟和亚叶酸钙方案治疗晚期胃癌的临床疗效及安全性优于ECF方案,值得临床推广应用。     

替吉奥治疗30例PS=2-3老年晚期胃癌临床观察

目的:观察替吉奥胶囊对PS=2-3老年晚期胃癌的治疗疗效及不良反应。方法:采用替吉奥治疗30例PS=2-3老年晚期进展期胃癌患者,对比16例最佳支持治疗患者,化疗2周期后评定疗效,并随访两组患者1年生存状况。结果:治疗组30例中28例可评价疗效和不良反应,治疗组和对照组的近期有效率分别为60.7%和43.8%(P<0.05),1年生存率分别为57.1%和50.0%(P>0.05)。两组PS评分变化无统计学差异,治疗组不良反应轻微,患者能耐受。结论:单药替吉奥方案是疗效较好的治疗PS=2-3老年晚期胃癌的化疗方案,不良反应轻,患者易于耐受。     

Postoperative adjuvant immunochemotherapy with mitomycin C,tegafur, PSK and/or OK-432 for gastric cancer,with special reference to the change in stimulation index after gastrectomy

In order to evaluate the efficacy of combined immunochemotherapy with mitomycin-C, tegafur, PSK and/or OK-432 as an adjunct for curatively resected gastric cancer, a prospective randomized controlled study using the envelope method was performed, in which 266 institutions from around Japan participated. The 3 year survival rates for all cases, and for ps(+)·n(+) cases, were insignificantly higher in the immunochemotherapy groups receiving PSK and/or OK-432 than in the control group. However, because 28.2 per cent of the cases were excluded from the final statistical analyses, the results of this study may have questionable statistical credibility. Changes in the stimulation index (SI) suggest that the administration of PSK may result in an inhibition of the immunosuppressive activity of cancer patients. The high SI group showed a significantly higher 4 year survival rate than the low SI group. The Cooperative Project No. 1 of the Japanese Foundation for Multidisciplinary Treatment of Cancer     

Which endpoints should we use in evaluating the use of novel fluoropyrimidine regimens in colorectal cancer?

Although significant advances have been made in the treatment of advanced/metastatic colorectal cancer, 5-fluorouracil (5-FU) still forms the basis of chemotherapy. Recently, new 5-FU schedules and novel fluoropyrimidines have been developed, but there are no trials directly comparing these regimens. The current review describes the mechanisms of action, pre-clinical and phase I/II studies of two oral fluoropyrimidine therapies, capecitabine and uracil with tegafur plus leucovorin. It also compares the phase III studies of these agents with those of the two most popular infusional 5-FU-based regimens: de Gramont and German AIO (The Association of Medical Oncology (AIO) of the German Cancer Society). Both oral and infusional regimens demonstrated similar survival to the Mayo Clinic regimen, a standard treatment for colorectal cancer. Therefore, other endpoints must be examined to decide optimum therapy, including response rates, time to disease progression, tolerability and patients' convenience. All four new therapies demonstrated superior safety profiles compared with the Mayo Clinic regimen. However the uracil with tegafur plus leucovorin regimen was associated with severe diarrhoea and capecitabine with hand-foot syndrome. Patients will not sacrifice efficacy for the convenience of oral therapy alone, therefore the fact that capecitabine achieved superior response rates and equivalent time to disease progression compared with the Mayo Clinic regimen, while uracil with tegafur plus leucovorin produced lower response rates and significantly inferior time to disease progression, is highly relevant in choosing treatment.     

Oral uracil and Ftorafur plus leucovorin: pharmacokinetics and toxicity in patients with metastatic cancer

Purpose: To assess the pharmacokinetics of Ftorafur (tegafur, FT), 5-fluorouracil (5-FU), and uracil in 31 cancer patients who were enrolled in phase I studies of oral uracil and FT (UFT). The correlation between pharmacokinetic parameters and toxic effects of UFT was evaluated. Methods: Uracil and FT were orally administered in a 4:1 molar ratio at FT doses of 200–400 mg/m² per day. Patients also received leucovorin at 150 mg/day. Daily doses were divided into three doses and administered at 8-h intervals for 28 consecutive days. Plasma FT concentrations were measured by high-performance liquid chromatography, and plasma 5-FU and uracil concentrations were determined using gas chromatography-mass spectrometry. National Institutes of Health Common Toxicity Criteria were used for assessment of toxicity. Results: The concentrations of FT, 5-FU, and uracil showed wide interpatient variations. Maximum plasma concentrations (Cp_max) of all three compounds were achieved in 0.3 to 4.0 h. At the various study doses, the terminal half-life (t_1/2β) of FT ranged from 3.9 to 5.9 h, the area under the concentration-versus-time curve (AUC_0–6h) ranged from 16,220 to 52,446 (ng/ml)h, the total clearance (Cl_T) ranged from 100 to 175 ml/min, and the steady-state volume of distribution (Vd_ss) ranged from 18.3 to 28.7 l. The 5-FU generated from FT had an apparent distribution half-life (t_1/2α) and an apparent elimination half-life (t_1/2β) of 0.3–1.3 h and 4.9–7.0 h, respectively. The AUC_0–6h of 5-FU ranged from 120 to 325 (ng/ml)h. Uracil had a t_1/2α of 0.2–0.5 h and the level quickly returned to the endogenous level. The AUC_0–6h for uracil ranged from 605 to 3764 (ng/ml)h, the Cl_T ranged from 3225 to 7748 ml/min, and the Vd_ss ranged from 341 to 1354 l. The Cp_max and AUC_0–6h of both FT and uracil were significantly correlated with FT doses (P-values of 0.0244 and 0.0112) and with uracil doses (P-values of 0.0346 and 0.0083), respectively. In addition to interpatient variations, intrapatient variations were also observed in six patients who had pharmacology studies done on days 1 and 26 ± 2 at the same study dose. We found that the repeated treatment with UFT caused cumulative increases in the values of Cp_max, C_trough, and AUC_0–6h of FT and 5-FU. The major toxic effects observed were diarrhea and nausea and vomiting. The occurrence of these toxic effects correlated significantly with the Cp_max and AUC_0–6h of 5-FU. Conclusions: The pharmacology studies showed that FT and uracil were readily absorbed orally and that FT was rapidly converted to 5-FU. The preliminary findings suggest that determination of plasma levels of 5-FU after oral administration of UFT may help predict subsequent toxic effects. Received: 2 September 1999 / Accepted: 14 April 2000     

高效液相色谱法测定辐射固化替加氟血药浓度

 目的：研究建立测定替加氟血药浓度的方法。方法：采用高效液相色谱法，测定不同给药方式的替加氟血药浓度。结果：本法灵敏度高，最低检测限为1.5ng·ml^-1，重现性好，操作简便。结论：本法为临床监测或血药浓度研究提供了一种简便、快速、微量、准确的分析手段。     

新型前体脂质体载药及影响因素考察

Aim A new proliposomal technology was used to trap several drugs, such as tegafur, silymarin, cistanosides, oleanolic acid. And then these proliposomal characters were studied. Methods These proliposomes formed liposomes after mixing with water. And then the liposomal morphology was determined by electron microscope, and the liposomal particle size determined by particle sizes instrument. The trap efficiency was determined by the column chromatography, and then the influence factors on the trap efficiency were investigated. Results The liposomes looked round, some with multiply layers, the particle was small, and the ξ potential was about -30 mV. The trap efficiency changed with the partition coefficient and pH. When the partition coefficient and pH increased, the trap efficiency increased. Furthermore, the trap efficiency was not influenced by the molecular weight. Conclusion This kind of liposomal technology trapped the drugs efficiently, and the lipophilic drugs were trapped more easily. Some Chinese traditional drugs could be trapped too.     

Adjuvant Ozonetherapy in Advanced Head and Neck Tumors: A Comparative Study

Advanced head and neck (H&N) tumors have a poor prognosis,and this is worsened by the occurrence of hypoxia and ischemiain the tumors. Ozonetherapy has proved useful in the treatmentof ischemic syndromes, and several studies have described apotential increase of oxygenation in tissues and tumors. Theaim of this prospective study was to evaluate the clinical effectof ozonetherapy in patients with advanced H&N cancer inthe course of their scheduled radiotherapy. Over a period of3 years, 19 patients with advanced H&N tumors who were undergoingtreatment in our department with non-standard fractionated radiotherapyplus oral tegafur. A group of 12 patients was additionally treatedwith intravenous chemotherapy before and/or during radiotherapy.In the other group of seven patients, systemic ozonetherapywas administered twice weekly during radiotherapy. The ozonetherapygroup was older (64 versus 54 years old, P = 0.006), with ahigher percentage of lymph node involvement (71% versus 8%,P = 0.019) and with a trend to more unfavorable tumor stage(57% versus 8% IVb + IVc stages, P = 0.073). However, therewas no significant difference in overall survival between thechemotherapy (median 6 months) and ozonetherapy (8 months) groups.Although these results have to be viewed with caution becauseof the limited number of patients, they suggest that ozonetherapycould have had some positive effect during the treatment ofour patients with advanced H&N tumors. The adjuvant administrationof ozonetherapy during the chemo–radiotherapy for thesetumors merits further research.     

射频消融术后应用奥沙利铂、替吉奥治疗中晚期肝癌的疗效及对血清CXCL13及LTBP2的影响

目的:探究射频消融术后应用奥沙利铂、替吉奥治疗中晚期肝癌的疗效及对血清CXCL13及LTBP2的影响。方法:选择2015年3月至2016年7月在我院接受治疗的80例中晚期肝癌患者为研究对象,采用随机数字分法分为观察组（射频消融联合奥沙利铂及替吉奥化疗组）与对照组（射频消融联合奥沙利铂组）,每组各40例。两组患者均给予射频消融术治疗,对照组术后给予奥沙利铂化疗,观察组术后给予奥沙利铂联合替吉奥治疗。观察比较两组患者术后肿瘤消融率以及临床疗效,采用酶联免疫法检测患者治疗前后血清CXCL13及LTBP2水平,依据欧洲癌症研究治疗组织系统开发的癌症病人生活质量测定量表体系中的核心量表（Quality of Life Questionnaire,QLQ-C30）,评估患者术前以及术后的生存质量,记录两组不良反应发生情况,定期对患者进行随访,评估远期预后。结果:两组患者术后肿瘤消除率无明显差异（P=0.556）,观察组治疗有效率（75.00%）明显高于对照组（52.50%）,差异具有统计学意义（P=0.036）;治疗前,两组患者血清CXCL13及LTBP2表达水平比较差异无统计学意义（P＞0.05）,治疗后两组血清CXCL13及LTBP2水平较治疗前均明显下降,且观察组显著低于对照组（P＜0.05）;治疗后,患者躯体功能、角色功能、社会功能、情绪功能、认知功能以及整体生活质量评分明显高于治疗前（P＜0.05）,并且观察组明显高于对照组（P＜0.05）。两组患者不良反应率无明显差异（25.00% vs 30.00%,P=0.617）。观察组患者肺癌复发与转移的发生率均明显低于对照组（P＜0.05）。结论:射频消融术后应用奥沙利铂、替吉奥可有效治疗中晚期肝癌,提高患者生存质量,抑制肿瘤复发转移,降低血清CXCL13及LTBP2水平,提高患者远期生存率。     

抗瘤增效方联合替吉奥治疗晚期结直肠癌疗效及对患者生存质量、血清肿瘤标志物的影响

目的:观察抗瘤增效方联合替吉奥治疗晚期结直肠癌疗效及对生存质量、血清肿瘤标志物的影响,并探讨其作用机制。方法:选取2013年1月至2015年12月确诊的100例晚期结直肠癌(advanced colorectal cancer,ACC)患者,随机分成两组,每组50例。对照组予替吉奥胶囊治疗,研究组在上述基础上予抗瘤增效方治疗。检测外周血T淋巴细胞和相关肿瘤标志物,评估生活质量,随访并记录各自生存时间,比较治疗效果和生存率。结果:与治疗前比较,对照组CD3~+,CD4~+,CD4~+/CD8~+降低(P0.01),CD8~+升高(P0.01);研究组CD3~+,CD4~+,CD4~+/CD8~+升高(P0.01),CD8~+降低(P0.01);两组癌胚抗原(carcinoembryonic antigen,CEA),肿瘤相关黏液抗原(carbohydrate antigen 242,CA242),糖链抗原19-9(carbohydrate antigen 19-9,CA19-9)均显著降低(P0.01),生活质量核心量表(Quality of Life Questionnaire-Core 30,QLQ-C30)功能领域评分升高(P0.01),QLQ-C30症状领域评分降低(P0.01);治疗后与对照组比较,研究组CD3~+,CD4~+,CD4~+/CD8~+较高(P0.01),CD8~+较低(P0.01),CEA,CA242,CA19-9较低(P0.01);QLQ-C30功能领域评分较高(P0.01),QLQ-C30症状领域评分较低(P0.01),客观缓解率(objective response rate,ORR)较高(P0.05),随访生存率较高(P0.05)。结论:抗瘤增效方联合替吉奥能提高ACC生存质量和生存率,治疗效果较理想,值得借鉴。