Ftorafur, adriamycin, cyclophosphamide and BCG in the treatment of metastatic breast cancer.

Ftorafur is a 5-fluorouracil analogue which is slowly metabolized to 5-FU, resulting in prolonged therapeutic levels of this latter drug. Ninety-one evaluable patients with metastatic breast cancer were treated with Ftorafur, Adriamycin, cyclophosphamide, and BCG (ACFTOR-BCG), in an attempt to increase the effectiveness of the program or decrease its myelosuppressive toxicity. The results of this trial were compared to those previously reported with the combination of 5-FU, Adriamycin, cyclophosphamide, and BCG (FAC-BCG). Overall objective response rates were 65% and 76% for ACFTOR-BCG and FAC-BCG, respectively. Durations of response were 12 months and 14 months for ACFTOR-BCG and FAC-BCG (p = 0.53). The median survival of responders was 22 and 23.9 months, respectively. Substantial toxicity was observed with Ftorafur: nausea and vomiting severe enough to cause weight loss was observed in a substantially higher fraction of the patients treated with this drug than with 5-FU. Other side-effects, which were not observed with the 5-FU combination, were somnolence, dizziness, personality changes, tremor, ataxia, and confusion. No differences in myelosuppressive toxicity were observed between the two combinations, and the incidence of infectious complications was identical. The combination of Ftorafur, Adriamycin, cyclophosphamide and BCG did not offer any advantages with respect to increased effectiveness or reduced toxicity over the FAC-BCG regimen in breast carcinoma.     

Oral Ftorafur Versus Intravenous 5-Fluorouracil: A comparative study in patients with colorectal cancer

The toxicities of ora] Ftorafur (1 g/m²/day 1-21) and intravenous 5-fluorouracil (5-FU) (500 mg/m²/day 1-5) were compared in a prospective randomized study in patients with colorectal cancer. The treatment courses were repeated every 6th week. Leu-copenia was more common after 5-FU. Leucocyte nadir in connection with first treatment cycle was on average seen on day 15 in patients receiving 5-FU and on day 28 in patients receiving Ftorafur. Significantly more patients on 5-FU developed stomatitis. There was no difference in the number of patients with diarrhea or nausea/vomiting. Median survival and response rates were not significantly different after the two treatment schedules.     

Phase II trial of UFT in advanced colorectal and gastric cancer

A phase II trial of continuous oral therapy with UFT, a combination of uracil and the 5-fluorouracil analogue 1-(2-tetrahydrofuryl)-5-fluorouracil (Futraful, Ftorafur), was conducted in 40 patients with advanced colorectal cancer and 18 patients with advanced gastric cancer. Six partial responses were seen in the 36 evaluable patients with colorectal cancer (response rate 16.6%; 95% confidence limits 6.4-32.8%), and one partial response was seen in the 16 evaluable patients with gastric cancer (response rate 6%; 95% confidence limits 0.27-30.2%). The overall toxicity of the treatment was low, and all patients were treated as outpatients. The results suggest that oral UFT has comparable activity to standard regimes of 5-fluorouracil, and because of the convenience of oral administration is a useful therapy in the management of patients with advanced colorectal cancer.     

Clinical evaluation of ftorafur (pyrimidine-deoxyribose n1-2'-furanidyl-5-fluorouracil).

Ftorafur, a possible sustained-release formulation of 5-fluorouracil, was administered to 27 patients with metastatic cancers. The majority of patients had adenocarcinoma, most of which (60%) arose from the gastrointestinal tract. Ftorafur was given i.v. at doses ranging from 1 to 3 g/sq m/day for 5 days, repeated every 2 to 3 weeks. Gastrointestinal (68%) and neurological (17%) toxicities were the most common side effects encountered in this study and became dose limiting at doses greater than 2 g/sq m/day for 5 days. Myelosuppression (7%) was infrequent. Other toxicities included weakness (20%), chills and fever (8%), and phlebitis (1%). Of 24 evaluable patients, 4 (17%) responded (1 complete and 3 partial remissions). Responses were seen in 1 of 8 carcinomas of the lung, 1 of 5 carcinomas of the stomach, 1 of 3 carcinomas of the colon, and 1 of 1 carcinoma of the jejunum. The duration of response ranged from 4 to 58 weeks. The results of this study resemble somewhat those obtained with the laborious 5-day continuous i.v. infusion of 5-fluorouracil. Daily doses of 2 g/sq m for 5 days, repeated every 3 weeks, produced significant antitumor effect and tolerable toxicity.     

Phase II trial of cisplatin and tegafur (Ftorafur) as initial therapy in squamous-cell carcinoma of the head and neck

Cisplatin and 5-fluorouracil infusion combination produces a high response rate in squamous-cell carcinoma of the head and neck. Tegafur (Ftorafur) is an analog of 5-fluorouracil, and its oral form is well absorbed. This agent has a moderate toxicity. We report a study to determine the efficacy of the cisplatin (100 mg/m2, day 1) and tegafur (1,000 mg/m2 daily for 21 days) combination. Thirty-nine patients entered the study; 36 were evaluable for response. Overall response was 94%, with a 22% complete response. Toxicity was moderate. We conclude that the cisplatin and tegafur combination is active in untreated patients with head and neck cancer.     

高能聚焦超声刀联合化疗治疗不能手术的结直肠癌肝转移的近期疗效

目的:探讨高能聚焦超声刀联合化疗治疗不能手术的结直肠癌肝转移的近期疗效及不良反应。方法:96例结直肠癌肝转移的患者,分为实验组和对照组。实验组48例,给予FOLFOX方案、FOLFIRI方案或单药卡培他滨口服方案,同时给予病灶局部高能聚焦超声刀,对照组的化疗方案与实验组相同。比较两组患者的疗效及不良反应。结果:实验组有效率为45.83%,而对照组治疗有效率为20.83%,差异有统计学意义（P=0.03）,不良反应分为血液学和非血液学不良反应,两组患者的不良反应无统计学差异（P>0.05）。结论:高能聚焦超声刀联合化疗可以提高结直肠癌肝转移治疗的有效率,且不增加患者不良反应。     

HLFO与LFO方案治疗大肠癌的对比研究

目的观察拓僖(hydroxycamptothecine,HCPT)联合亚叶酸钙(LV)、氟尿嘧啶(5-Fu)、草酸铂(L-OHP)组成的HLFO方案治疗大肠癌的近期疗效和毒性反应,并与后三种药组成的LFO方案进行比较.方法采用随机的方法将83例大肠癌患者分为HLFO方案组(A组)41例和LFO方案组(B组)42例.均每21 d为一周期,连续治疗3个周期.结果 HLFO组有效率为52.6%(10/19),LFO组45.5%(10/22),差异无显著性.两组主要毒副反应相似,均为骨髓抑制、消化道反应和神经毒性.结论 HLFO方案较LFO方案疗效有提高趋势,可通过扩大观察病例数量和增加化疗周期来进一步评价其临床价值.     

低剂量顺铂联合5-氟尿嘧啶周疗同步放疗治疗中晚期宫颈癌

目的 评价低剂量顺铂(DDP)+5-氟尿嘧啶(5-Fu)周疗同步放疗治疗中晚期宫颈癌的疗效和不良反应.方法 73例中晚期宫颈癌患者随机分为化放组(37例)和单放组(36例).化放组放疗同期每周接受1次DDP 40 mg+5-FU 500 mg化疗,连用6～7周;单放组行单纯放疗.两组放疗均采用常规分割,总剂量50 Gy.结果 化放组与单放组总有效率、3年生存率、局部复发率、远处转移率分别为97.30%和77.78%、89.19%和66.67%、8.11%和30.56%、10.81%和33.33%,两组对比差异均有统计学意义(P<0.05),骨髓抑制及消化道反应发生率化放组均高于单放组,多为Ⅰ、Ⅱ级.结论 低剂量DDP+5-FU周疗同步放疗治疗中晚期宫颈癌可显著提高患者的局部控制率和生存率,不良反应轻.     

In vitro biological evaluation of the R and S isomers of 1-(Tetrahydrofuran-2-yl)-5-fluorouracil.

The S isomer of Ftorafur was synthesized and the ability of the latter to inhibit growth of cultured human fibroblasts was determined relative to both the R isomer and the racemic mixture (Ftorafur) that is presently used clinically. No significant difference in the cytotoxic effects or the relative abilities to prevent an increase in cell numbers was observed with the three forms. Inhibition of DNA synthesis in murine L1210 leukemia cells by either isomer was observed only after prolonged (18-hr) exposure. The data suggest that Ftorafur is a repository form of 5-fluorouracil and that activity is manifested equally by both isomers.     

Potent effects of adjuvant chemotherapy using 5-fluorouracil + leucovorin on DNA aneuploid colorectal cancer

Background The relationship between DNA ploidy of colorectal cancer cells and sensitivity to adjuvant chemotherapy, using 5-fluorouracil+leucovorin was investigated. Methods Seventy-five patients with Duke's B or C colorectal cancer, who underwent potentially curative resection, were randomly allocated to 2 groups. Thirty-eight patients received adjuvant chemotherapy using 5-fluorouracil+leucovorin (chemotherapy group), and 37 patients received no adjuvant chemotherapies (no-chemotherapy group). Tumor cell ploidy of all patients was analyzed using paraffin-embedded samples. Results There was no statistically significant difference in overall survival between patients who received chemotherapy and those who did not. Among the patients with diploid tumors (n=39), there was no significant difference in survival between the chemotherapy group (n=20, 5-year survival rate of 34.3%) and the no-chemotherapy group (n=19, 5-year survival rate of 27.1%). By contrast, among the aptients with aneuploid tumors (n=36), the survival rate was significantly better in the chemotherapy group (n=18, 5-year survival rate of 77.8%), than in the no-chemotherapy group (n=18, 5-year survival rate of 43.7%) (P=0.023). Conclusion These results suggest that aneuploid tumors are more sensitive to adjuvant chemotherapy, using 5-fluorouracil+leucovorin, than are diploid tumors.     

Prospective randomized trial comparing modified FAM (5-fluorouracil (5-FU) + adriamycin + mitomycin C) versus 5-FU alone for the treatment of non-resectable pancreatic and biliary tract carcinomas (the 1st trial in non-resectable patients). Study Group of Surgical Adjuvant Therapy for Carcinomas of the Pancreas and Biliary Tract]

The modified FAM (5-fluorouracil (5-FU) + adriamycin (ADR) + mitomycin C (MMC)) therapy (FAM group) was compared with 5-FU mono-therapy (F group) by multi-institutional randomized trial in the patients with cancer of the pancreas or the biliary tract who underwent non-resection. The patients in FAM group received 6 mg/m2 of i.v. MMC during operation, 310 mg/m2 of i.v. 5-FU for 5 days in the 1st and 3rd postoperative weeks and 12 mg/m2 of i.v. ADR in the 2nd postoperative week. Those in F group received only 5-FU course in the administration schedule of FAM group. Among the cases which completed respective whole administration schedules. 35 cases in FAM group and 36 in F group, better effect than partial response (PR) was observed in neither groups, and there was no significant difference between groups with respect to overall/each disease survival duration, progression-suppressed duration and clinical effect. Primary adverse effects were alimentary symptoms and hepatic dysfunction, neither of which was serious, and there was no difference between groups except that hair loss was observed in more cases in FAM group (p less than 0.05). Results in FAM group did not statistically surpass those in F group, but a tendency was observed that FAM group was better than F group in terms of survival duration and clinical effect for cancer of the gall-bladder.     

Modelling of ftorafur and 5-fluorouracil pharmacokinetics following oral UFT administration. A population study in 30 patients with advanced breast cancer

PURPOSE: The pharmacokinetics of ftorafur, 5-fluorouracil (5FU) and uracil were investigated in order to built a population pharmacokinetic model for the anticancer drug UFT, administered with leucovorin and vinorelbine. METHODS: A total of 31 patients with metastatic breast cancer were treated with escalating oral doses of UFT (300 to 500 mg per day) plus leucovorin (90 mg per day) in combination with intravenous vinorelbine (15 to 25 mg/m(2)). Concentration-time data were obtained on days 1, 8, 15 and 21 of cycle 1. RESULTS: Of the 31 patients treated, 30 were available for the pharmacokinetic analysis. Ftorafur, 5FU and uracil appeared rapidly in plasma and showed large interpatient variations. Ftorafur concentrations were higher than those of 5FU and uracil. AUC significantly increased between day 1, and days 8, 15 and 21. Ftorafur C(max) and AUC values were proportional to UFT dose, whereas C(max) and AUC values of 5FU and uracil were not linearly related to UFT dose. The pharmacokinetics of ftorafur were ascribed to a two-compartment open model in which 5FU was produced from the central compartment. The absorption and exponential distribution rate constants were assumed equal. The effect of uracil on 5FU elimination was straightforward, since no reasonable curve-fitting could be obtained for 5FU data when this covariate was not taken into account. The uracil concentration inducing a 50% reduction in 5FU elimination was 2.67 micro mol.l(-1). This result confirms the important role played by uracil as a competitive inhibitor of 5FU catabolism. CONCLUSION: A pharmacokinetic model for ftorafur and 5FU was developed and should be useful to further study drug interactions and establish dosing guidelines.     

化疗联合调强放疗治疗食管癌的疗效及不良反应评价

目的探讨化疗联合调强放疗在食管癌治疗中的应用价值。方法按照治疗方案的不同将120例食管癌患者分为对照组和观察组,各60例。全部患者均接受5-氟尿嘧啶+顺铂化疗,对照组患者同时接受常规放疗,观察组患者同时接受调强放疗。比较两组患者的近期疗效。结果观察组患者的治疗总有效率为88.33%(53/60),明显高于对照组患者的58.33%(35/60),差异有统计学意义(P﹤0.01)。两组患者均发生了放疗相关不良反应,包括放射性食管炎、放射性肺炎、骨髓抑制;观察组患者的放疗相关不良反应的发生率均明显低于对照组,差异均有统计学意义(P﹤0.01)。结论食管癌患者在接受化疗的同时接受调强放疗,既可以提高近期疗效,又可以减少放射不良反应的发生,治疗安全性较高。     

动脉持续灌注化疗与静脉全身化疗治疗中晚期胰腺癌的疗效分析

Objective: To compare the curative effectiveness of continuous transarterial infusion chemotherapy and systemic venous chemotherapy in treating patients with advanced pancreatic cancer, and to evaluate the value of selective continuous transarterial infusion chemotherapy in treating advanced pancreatic cancer. Methods: Of the 51 patients with advanced pancreatic cancer receiving chemotherapy with gemcitabine and 5-fluorouracil, 25 patients were treated with selective continuous transarterial infusion chemotherapy, 26 were treated with systemic venous chemotherapy, and curative effectiveness was analyzed retrospectively. Curative effectiveness included tumor volume, clinical benefit response (CBR), acute and subacute toxic reactions of antitumor drugs, survival rate and median survival time. Results: The objective effective rate in transarterial group was 32.0% versus 23.1% in systemic group without any significant difference (P = 0.475). Clinical benefit rates in transarterial group and systemic group were 80.0% and 50.0% respectively (P = 0.025). The 6-, 9- and 12-month accumulated survival rates and median survival time in transarterial group were higher than those of the systemic group (P = 0.002), the differences were statistically significant. However, the adverse reactions between the two groups were not statistically significant. Conclusion: Compared with systemic chemotherapy, continuous transarterial infusion chemotherapy with gemcitabine and 5-fluorouracil could improve clinical benefit rate and survival time of patients with advanced pancreatic cancer, it is safe and reliable, and the adverse reactions is less.     

动脉持续灌注化疗与静脉全身化疗治疗中晚期胰腺癌的疗效分析

Objective: To compare the curative effectiveness of continuous transarterial infusion chemotherapy and systemic venous chemotherapy in treating patients with advanced pancreatic cancer, and to evaluate the value of selective continu-ous transarterial infusion chemotherapy in treating advanced pancreatic cancer. Methods: Of the 51 patients with advanced pancreatic cancer receiving chemotherapy with gemcitabine and 5-fluorouracil, 25 patients were treated with selective con-tinuous transarterial infusion chemotherapy, 26 were treated with systemic venous chemotherapy, and curative effective-ness was analyzed retrospectively. Curative effectiveness included tumor volume, clinical benefit response (CBR), acute and subacute toxic reactions of antitumor drugs, survival rate and median survival time. Results: The objective effective rate in transarterial group was 32.0% versus 23.1% in systemic group without any significant difference (P = 0.475). Clinical benefit rates in transarterial group and systemic group were 80.0% and 50.0% respectively (P = 0.025). The 6-, 9-and 12-month accumulated survival rates and median survival time in transarterial group were higher than those of the systemic group (P = 0.002), the differences were statistically significant. However, the adverse reactions between the two groups were not statistically significant. Conclusion: Compared with systemic chemotherapy, continuous transarterial infusion chemotherapy with gemcitabine and 5-fluorouracil could improve clinical benefit rate and survival time of patients with advanced pancreatic cancer, it is safe and reliable, and the adverse reactions is less.     

Chemoimmunotherapy with or without oophorectomy in premenopausal patients with advanced breast cancer.

Ninety-eight premenopausal patients with stage IV breast cancer were treated with chemoimmunotherapy alone, or with combination oophorectomy-chemoimmunotherapy either simultaneously (chemoimmunotherapy within four weeks of oophorectomy) or sequentially (delayed chemoimmunotherapy until evidence of progressive disease or no response to oophorectomy). The chemoimmunotherapy consisted of a three-drug combination of Adriamycin, cyclophosphamide, and 5-fluorouracil or Ftorafur; immunotherapy consisted of either oral levamisole, BCG by scarification, or a combination of both. Forty patients underwent simultaneous oophorectomy-chemoimmunotherapy, with a response rate of 85% and a median duration of response of 25 months. Response rate of 69% and a median duration of response of 16.6 months was observed with the 29 patients who received sequential oophorectomy-chemoimmunotherapy. Another 29 patients were treated with chemoimmunotherapy alone and achieved a response rate of 87% and a median duration of response of 11.8 months. Though there were no significant differences in the response rate, patients treated with chemoimmunotherapy alone had a significantly shorter median duration of response (P less than 0.05). This would suggest that oophorectomy in combination with chemoimmunotherapy is the most favorable treatment modality for premenopausal patients with advanced metastatic breast cancer.     

Phase I-II study of ftorafur and methyl-CCNU in advanced colorectal cancer.

The combination of Ftorafur (NSC-148958) and methyl-CCNU (NSC-95441) was evaluated in 36 patients with advanced colorectal cancer. The principle toxicities encountered were myelosuppression, gastrointestinal, and neurological. There were no complete responses and only 5/34 (14.7%) patients achieved a partial response. Methyl-CCNU and Ftorafur does not appear to be an effective combination in advanced adenocarcinoma of the colon and rectum.     

经动脉持续灌注化疗治疗中晚期胰腺癌的临床分析

 目的 比较经动脉持续灌注化疗和全身静脉化疗治疗中晚期胰腺癌的临床疗效，探讨选择性动脉持续灌注化疗的临床应用价值。方法 51例中晚期胰腺癌，其中25例采用经动脉持续灌注吉西他滨和5-Fu方案，26例采用经外周静脉灌注吉西他滨和5-Fu方案。应用世界卫生组织实体瘤疗效评定标准评价疗效，肿瘤体积测量采用MRI或CT。使用临床受益反应（CBR）对疼痛、体力状况及体重改变情况作出综合评价。采用WH0抗肿瘤药物急性与亚急性毒性分级标准对不良反应进行评价。结果 动脉灌注化疗组的有效率（32．0％）高于外周静脉化疗组（23．1％），但差异无显著性。动脉灌注化疗组的临床受益率（80．0%）高于外周静脉化疗组（50．0％），差异有显著性。6个月、9个月、1年的累积生存率和中位生存时间，动脉灌注化疗组高于外周静脉化疗组，差异有显著性。按WHO分级标准，两组患者不良反应之间无显著性的差异。结论 经动脉持续灌注吉西他滨和5-Fu较外周静脉灌注吉西他滨和5-Fu能提高中晚期胰腺癌的临床受益率和生存期，其方法安全可靠，且不良反应少。     

5-Fluorouracil dose intensity increase in 5-fluorouracil and leucovorin combination: results of a phase II study

It was our intention to verify if in the combination of 5-fluorouracil and leucovorin, the fluoropyrimidine dose intensity is an important determinant of response as noted by Hryniuk when 5-fluorouracil was given alone. By employing the Machover regimen but with cycles repeated every three weeks, a 5-fluorouracil projected dose intensity of 616 mg/m2/wk was obtained. It approximates the maximum tolerated dose for this drug when used alone by i.v. bolus. 50 patients entered this study and 48 were evaluable for response and toxicity. The overall response rate was 29% (five complete responses and nine partial responses). The dose limiting toxicity was gastrointestinal rather than myelosuppression. 5-fluorouracil dose reduction was needed in seven patients. The mean delivered dose intensity of 5-fluorouracil was 610 mg/m2/wk (582 mg/m2/wk in patients in whom 5-fluorouracil was reduced for toxicity and 616 mg/m2/wk in the others). Our results do not seem to show any advantage in the maximization of 5-fluorouracil dose intensity. Furthermore, in an analysis of data from the literature we did not find any difference in response rate in relation to dose intensity in the 5-fluorouracil/leucovorin combination.     

TCF方案与PF方案治疗晚期食管癌的临床研究

目的:观察比较紫杉醇联合顺铂、氟尿嘧啶(TCF方案)与顺铂加氟尿嘧啶(PF方案)两个方案治疗晚期食管癌的临床疗效和毒性反应。方法:共69例患者,分别用TCF、PF方案化疗,28天为1个周期。2个周期以后按照WHO标准进行疗效评价。结果:TCF方案可评价疗效者32例,CR2例,PR15例,有效率53.1%。中位疾病进展时间为5.4个月,中位生存时间10.1个月。可评价毒副反应33例。主要不良反应为脱发、中性粒细胞降低,恶心、呕吐也较常见。PF方案可评价疗效者29例,PR14例,有效率48.3%。中位疾病进展时间3.9个月,中位生存期8.7个月。主要不良反应为恶心、呕吐。结论:TCF方案对晚期食管癌疗效好,毒副反应可耐受,可以考虑作为治疗晚期食管癌的主要治疗方案。