高效液相色谱法测定人体血浆中替加氟的方法研究

目的建立一种高效液相色谱法测定人体血浆中替加氟浓度的方法。方法色谱柱为Zorbax-ODS C18(250 mm×4.6mm,5μm),检测波长为273 nm,流动相为0.01 mol/L磷酸盐(用磷酸溶液调pH 5.2)-甲醇(85∶15),流速1.0 mL/min,柱温为35℃。结果替加氟血药浓度在0.1~20μg/mL(r=0.999 7)内线性关系良好,最低检测浓度为0.1μg/mL,绝对回收率均在95%以上,相对回收率在94%~104%,日内、日间RSD分别为3.0%和4.1%。结论本方法简单、快速、准确,适用于临床药动学研究及血药浓度监测。     

Weekly irinotecan plus UFT and leucovorin as first-line chemotherapy of patients with advanced colorectal cancer

Summary We evaluated the antitumoral efficacy and safety of CPT-11 125 mg/m² (weekly 90 min i.v. infusion; days 1, 8 and 15) combined with UFT (oral combination of tegafur and uracil) 200 mg/m²/day plus leucovorin (LV) 45 mg/m²/day (both divided into three separate oral doses every 8 h, days 1–21) every 4 weeks as first-line chemotherapy of metastatic colorectal cancer (CRC). Fifty-three patients 18 years old with histologically confirmed diagnosis of advanced CRC and bidimensionally measurable disease were enrolled. Three patients (6%) showed CR and 8 patients (15%) showed PR (ORR = 21% (95% CI, 10–32). Stable disease was reported in 19 patients (36%) [tumor control rate = 57% (95% CI, 43–70)]. The median time to progression and overall survival were 7.9 and 18.2 months, respectively (1-year rate = 74%; 2-years rate = 26%). CPT-11/UFT/LV treatment was well tolerated: the most reported grade 3/4 toxicities were neutropenia (11% of patients) and delayed diarrhea (28% of patients). No significant differences in response rate, survival or toxicity were found between younger (65 years) and older patients (> 65 years). Weekly CPT-11 plus UFT/LV was found effective and safe as first-line chemotherapy for metastatic CRC. The addition of CPT-11 to UFT/LV doubled the response rate compared to the results previously reported with UFT/LV, while myelosuppression remained low.     

替吉奥胶囊处方优选

目的筛选替吉奥胶囊的最佳处方组成.方法以辅料中的乳糖、十二烷基硫酸钠、硬脂酸镁作为考察因素,每个因素取3个水平,用L9（34）正交表安排试验,以替吉奥胶囊的溶出度为主要考察指标,以颗粒流动性和外观为参照指标,进行正交试验.结果辅料中影响胶囊溶出度的主要因素是十二烷基硫酸钠（P＜0.05）,最佳处方组成为乳糖60 g,十二烷基硫酸钠4 g,硬脂酸镁1.5 g.结论采用该处方及工艺制得的替吉奥胶囊溶出度较高,而且产品质量稳定,制备工艺简单可行,适合工业化大生产.     

The clinical and economic benefits of capecitabine and tegafur with uracil in metastatic colorectal cancer

Two oral fluoropyrimidine therapies have been introduced for metastatic colorectal cancer. One is a 5-fluorouracil pro-drug, capecitabine; the other is a combination of tegafur and uracil administered together with leucovorin. The purpose of this study was to compare the clinical effectiveness and cost-effectiveness of these oral therapies against standard intravenous 5-fluorouracil regimens. A systematic literature review was conducted to assess the clinical effectiveness of the therapies and costs were calculated from the UK National Health Service perspective for drug acquisition, drug administration, and the treatment of adverse events. A cost-minimisation analysis was used; this assumes that the treatments are of equal efficacy, although direct randomised controlled trial (RCT) comparisons of the oral therapies with infusional 5-fluorouracil schedules were not available. The cost-minimisation analysis showed that treatment costs for a 12-week course of capecitabine (Pounds 2132) and tegafur with uracil (Pounds 3385) were lower than costs for the intravenous Mayo regimen (Pounds 3593) and infusional regimens on the de Gramont (Pounds 6255) and Modified de Gramont (Pounds 3485) schedules over the same treatment period. Oral therapies result in lower costs to the health service than intravenous therapies. Further research is needed to determine the relative clinical effectiveness of oral therapies vs infusional regimens.     

Adjuvant chemotherapy with uracil-tegafur for pathological stage III rectal cancer after mesorectal excision with selective lateral pelvic lymphadenectomy: a multicenter randomized controlled trial

BACKGROUND: Although adjuvant radiotherapy was proved to be effective for local control of rectal cancer even after standardized mesorectal excision, the role of adjuvant chemotherapy after such standardized surgery remains to be clarified. We aimed to assess the efficacy of a combination of uracil and tegafur for pathological stage III rectal cancer treated by standardized mesorectal excision with selective lateral pelvic lymphadenectomy. METHODS: We randomly assigned patients with completely resected stage III rectal cancer, who underwent standardized mesorectal excision with selective lateral pelvic lymphadenectomy, to receive either oral uracil-tegafur (400 mg/m2 tegafur per day) for one year or no treatment. Standardization and quality control of the surgery and pathological techniques were ensured by use of the guidelines of the Japanese Society for Cancer of the Colon and Rectum. The primary endpoint was relapse-free survival. The secondary endpoint was overall survival. RESULTS: We enrolled and randomized 276 patients. Excluding two ineligible patients, 274 were included in the analysis. Planned interim analysis 2 years after accrual termination revealed significant prolongation of relapse-free survival (P = 0.001) and overall survival (P = 0.005) in the uracil-tegafur group. The 3-year relapse-free survival and overall survival rates were 78 and 91% in the chemotherapy group and 60 and 81% in the surgery-alone group, respectively. Local recurrence rates were low in both groups. Grade 3 events occurred in 17% of the chemotherapy patients, but no grade 4 or more events occurred. CONCLUSION: Adjuvant chemotherapy with uracil-tegafur improves survival of patients with stage III rectal cancer after standardized mesorectal excision with selective lateral pelvic lymphadenectomy.     

优福定片中二组分的紫外吸收比法测定

利用等吸光点处（２７１．５ｎｍ）混合组分的吸光系数和尿嘧啶在λｍａｘ２５９ｎｍ处的吸光度，采用紫外吸收比法同时测定优福定片中二组分的含量。方法简便、快速、准确，重现性好。喃氟啶和尿嘧啶的回收率分别为１００．７±０．７％和１００．２±０．４６％（ｎ＝５）。     

A phase I/II study of oral uracil/tegafur (UFT), leucovorin and irinotecan in patients with advanced colorectal cancer.

BACKGROUND: The aim of this study was to determine the maximum tolerated dose (MTD), toxicity profile and response rate of the oral 5-fluorouracil prodrug UFT (tegafur/uracil) and leucovorin (LV) in combination with irinotecan in patients with advanced or metastatic colorectal cancer. PATIENTS AND METHODS: Patients with histologically proven advanced or metastatic colorectal adenocarcinoma received first-line chemotherapy comprising UFT 250 mg/m(2)/day and LV 90 mg/day given on days 1 to 14, with escalating doses of irinotecan (200-300 mg/m(2)) administered intravenously on day 1 of a three-weekly cycle. Eligibility criteria were standard. The MTD was defined as the dose at which >33% of six patients experienced a dose-limiting toxicity (DLT) during cycle 1. RESULTS: A total of 32 patients were studied. Initially, six patients were treated at each of the irinotecan dose levels (200, 250 and 300 mg/m(2)) combined with UFT 250 mg/m(2)/day and LV 90 mg/day. DLTs consisting of grade 3 or 4 diarrhoea and febrile neutropenia were observed in one of 20 patients at 250 mg/m(2) and three of six patients at the 300 mg/m(2) irinotecan dose level. Having defined the MTD, the 250 mg/m(2) dose level was established as the recommended dose (RD) and expanded to 20 patients in whom treatment was generally well tolerated. The overall response rate was 19%, with five patients having a partial response (PR) and 18 stable disease (SD) out of 32 response-evaluable patients. CONCLUSION: UFT and LV can be safely combined with irinotecan. The RDs for future studies are UFT 250 mg/m(2)/day and LV 90 mg/day given on days 1-14, with irinotecan 250 mg/m(2) administered on day 1, every 3 weeks. This combination is well tolerated and active. Further investigation of UFT and LV in combination with irinotecan is warranted in patients with colorectal cancer.     

晚期胆囊癌应用吉西他滨联合替吉奥方案化疗的临床疗效

目的探索晚期胆囊癌中吉西他滨联合替吉奥化疗的近期临床疗效和毒副反应。方法对20例晚期胆囊癌患者采用吉西他滨联合替吉奥方案化疗,吉西他滨1000 mg/m2,第1、5天静脉给药;替吉奥60 mg/m2/d,分两次口服,持续口服14天,三周为1周期,至少应用两周期,两疗程后评价患者的疗效、毒副反应等。结果入组20例均可评价疗效,治疗后完全缓解1例,部分缓解5例、稳定8例、进展6例,总有效率为30%,肿瘤控制率70%。无严重不良事件发生,无1例死亡,主要的不良反应为骨髓抑制、恶心呕吐、皮疹、肝功能损害。结论晚期胆囊癌应用吉西他滨联合替吉奥化疗的近期疗效较好,毒性反应较轻,患者耐受性可。     

5-氟尿嘧啶及其衍生物对原发性肝癌的疗效分析

5FU常被用于治疗原发性肝癌,其衍生物如FUDR,FT207及FD1等采用适当的给药途径与剂量对原发性肝癌有一定的疗效,与对照组相比,有效率、生存期及半年生存率等皆有显著提高,其中尤以经肝动脉导管灌注5FU,FUDR及口服FT207,FD1为佳.5FU及其衍生物毒性反应不大,对未能切除或不宜切除的某些原发性肝癌病例使用,可能使其中部份病例获得缓解之机会.     

替吉奥单药与XELOX方案一线治疗老年晚期胃癌的疗效比较

目的:比较替吉奥单药与XELOX方案一线治疗老年晚期胃癌的疗效及不良反应.方法:将41例老年进展期胃癌患者随机分为单药组和联合化疗组.单药组20例,替吉奥单药口服,每次40~60 mg(体表面积<1.25 m2剂量为每次40 mg;体表面积为1.25~1.5 m2剂量为每次50 mg;体表面积>1.5 m2为每次60 mg),每天2次,连用14 d,每3周重复;联合化疗组21例,XELOX方案化疗,奥沙利铂130 mg/m2,静脉滴注3 h,第1天;卡培他滨1000 mg/m2,每天2次,连服14 d,每3周重复.每用药2个周期后评价疗效.结果:单药组有效率30.0%、疾病控制率65.0%,中位无进展生存时间为5.6个月;联合化疗组有效率42.9%,疾病控制率66.7%,中位无进展生存时间为6.2个月.2组差异均无统计学意义(P>0.05).联合化疗组的周围神经毒性发生率高于单药组(P<0.05),其他化疗不良反应发生率差异均无统计学意义(P>0.05).结论:替吉奥单药治疗老年进展期胃癌可取得不弱于联合化疗方案的近期疗效,且有较低的不良反应.