Phase II trial of oral uracil/tegafur plus leucovorin in patients with hormone-refractory prostate carcinoma

BACKGROUND: The current study evaluated the efficacy of oral uracil/tegafur (UFT) and leucovorin (LV) in patients with hormone-refractory metastatic prostate carcinoma. METHODS: Twenty-eight patients with hormone-refractory metastatic carcinoma of the prostate who had undergone antiandrogen withdrawal and no more than 1 prior chemotherapy treatment were enrolled on a single-institution Phase II trial. Patients were treated with oral UFT at a dose of 300 mg/m2/d and oral LV at a dose of 90 mg/day for 28 days followed by 7 days off therapy on a 35-day cycle regimen. RESULTS: Twenty-six patients were evaluable for response and toxicity. There was no response by objective criteria in 9 patients with measurable disease. Four responses by prostate-specific antigen (PSA) criteria (i.e., PSA decrease by > 50%) were noted (15%) lasting a mean of 20.5 weeks. Therapy was generally well tolerated, with 2 patients developing Grade 4 toxicity (1 patient each with diarrhea and hand-foot syndrome) and 4 patients having significant Grade 3 toxicity (anemia, hyperbilirubinemia, and vomiting) (Toxicity was graded according to the National Cancer Institute Common Toxicity Criteria). Six patients had stable disease by clinical, laboratory, and radiologic criteria for an average of 5 cycles of treatment (25 wks). CONCLUSIONS: Although UFT and LV are generally well tolerated in the setting of hormone-refractory metastatic prostate carcinoma, the combination has a low level of activity. Its toxicity and activity is similar to that observed when intravenous 5-fluorouracil or capecitabine are given alone. It may be an option for further investigations in combination regimens.     

The efficacy of epirubicin, cisplatin, uracil/tegafur, and leucovorin in patients with advanced biliary tract carcinoma

BACKGROUND: Advanced biliary tract carcinoma is among the most prevalent fatal diseases in Korea. However, to our knowledge, to date no effective therapeutic modality has been shown to prolong the survival of patients in the inoperable stages of this disease. METHODS: This Phase II study was conducted to determine the efficacy and toxicity of a combined regimen of epirubicin, cisplatin, and uracil/tegafur (UFT) modulated by leucovorin in patients with advanced or recurrent biliary tract carcinoma. RESULTS: Eleven of 40 patients (27.5%) had gallbladder carcinoma, and the remaining patients had tumors arising from other sites in the biliary tract. All patients were treated with intravenous epirubicin (50 mg/m(2) on Day 1), intravenous cisplatin (60 mg/m(2) on Day 1), oral UFT (300 mg/m(2) per day on Days 1-21), and oral leucovorin (75 mg per day on Days 1-21). Nine patients exhibited a partial response, representing 22.5% of the possible response rate (95% confidence interval [95% CI], 12.8-32.2%) based on an intention-to-treat analysis. The median survival was 34 weeks (95% CI, 20-48 weeks), and the median time to disease progression was 16 weeks (95% CI, 7-25 weeks). Neutropenia and thrombocytopenia comprised dose-limiting toxicity conditions. CONCLUSIONS: The combination of epirubicin, cisplatin, and UFT modulated by leucovorin was active marginally in patients with advanced biliary tract carcinoma and was capable of stabilizing the disease effectively. Because it was a safe and convenient treatment modality, it may be used in outpatient care with only minor toxicity in patients with advanced malignancies of the biliary tract.     

Phase II study with a combination of epirubicin, cisplatin, UFT, and leucovorin in advanced hepatocellular carcinoma

Purpose: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Because HCC usually presents as an advanced disease and occurs in the background of liver cirrhosis, most patients are not suitable for treatment with curative intent, thus effective systemic chemotherapy is required. However, the outcome of systemic chemotherapy has been disappointing in advanced HCC. This study was conducted to test the efficacy and toxicity of the combined regimen of epirubicin, cisplatin, and UFT moderated by leucovorin in advanced or recurrent HCC. Patients and methods: All 53 patients received epirubicin (50 mg/m² i.v.) on day 1 and cisplatin (60 mg/m² i.v.) after epirubicin administration. Oral UFT 400–600 mg/day, determined by body surface area, and leucovorin 75 mg/day were administered for 21 consecutive days, followed by a 7-day drug free interval. Results: Nine had a partial response, representing 16.9% of response rate (95% confidence interval rate; 7.0–26.8%) with median response duration of 17.1 weeks (95% CI; 5.0–29.3 weeks, range; 7.1–51.7 weeks). Fifteen patients had stable disease and the disease progressed in 26 patients. The median overall survival for the patients was 24.6 weeks (95% CI; 17.3–31.9 weeks, range; 3.0–131.3 weeks). The main toxicities were hematologic toxicities including neutropenia, which reached grade 3/4 in 17 patients (38.5%), and grade 3 or 4 thrombocytopenia in five patients (9.4%). Conclusion: The combination of epirubicin, cisplatin, and UFT moderated by leucovorin showed modest anti-tumor activity with relatively tolerable toxicities. However, a randomized phase III trial based on this regimen is warranted to clarify its survival benefit in patients with advanced HCC. Contract grant sponsor: Brain Korea 21 Project in 2002 and Korea Health 21 R &D Project, Ministry of Health & Welfare, Republic of Korea: 01-PG3-PG6-01GN07-0004.     

Phase II trial of uracil/tegafur (UFT) plus leucovorin in patients with advanced pancreatic carcinoma: A University of Chicago phase II consortium study

Background/objectives: Uracil and tegafur in a 4 : 1 molar concentration ratio (UFT; Bristol-Myers Squibb, Wallingford, CT) has broad anti-tumor activity for cancers arising from the gastrointestinal tract. However, there are no published data regarding the efficacy of leucovorin-modulated UFT in patients with pancreatic cancer. The objective of this trial was to determine the activity and evaluate the toxicity of UFT plus oral calcium leucovorin in patients with advanced pancreatic adenocarcinoma.Patients and methods: Fourteen patients with advanced measurable adenocarcinoma of the pancreas were enrolled onto the trial. Patients received 300 mg/m²/d UFT plus 90 mg/d leucovorin administered orally in divided doses every eight hours for 28 days repeated every 35 days. Objective tumor response was evaluated after two courses of therapy.Results: Fourteen patients were evaluable for response and toxicity. No objective responses were seen. The median (range) time to progression and survival were 14 (1.6–37), and 15 (1.9–62) weeks, respectively. Toxicity was mild with severe (grade 3 or 4) hyperbilirubinemia, pain, diarrhea, transaminitis, venous thrombus, weakness, renal failure, confusion, and edema/ascites seen in three (21%), one (7%), two (14%), one (7%), one (7%), one (7%), one (7%), one (7%), and two (14%) patients, respectively.Conclusion: In the 14 patients evaluable, UFT 300 mg/m²/d plus oral leucovorin 90 mg/d administered for 28 days did not demonstrate anti-tumor activity against advanced pancreatic adenocarcinoma; however, this oral regimen was well tolerated and devoid of neutropenia, significant oral mucositis or diarrhea.     

A phase II study of weekly docetaxel and cisplatin plus oral tegafur/uracil and leucovorin as first-line chemotherapy in patients with locally advanced or metastatic gastric cancer

Background:

Docetaxel plus cisplatin and 5-fluorouracil has become a new standard for treating advanced gastric cancer. However, high rates of severe neutropenia limit its application. Modification of the regimen could be the solution to get similar activity but less myelosuppression.

Methods:

Patients with histologically confirmed, locally advanced, or recurrent/metastatic gastric adenocarcinoma without previous chemotherapy were enrolled. This regimen consisted of docetaxel (Tyxan, TTY, Taipei, Taiwan) 30-min infusion at a dose of 36 mg m⁻², followed by cisplatin 30 mg m⁻² infusion over 1 h on days 1 and 8, and oral tegafur/uracil 300 mg m⁻² per day plus leucovorin 90 mg per day on days 1–14, every 3 weeks. Tumour response was evaluated after every 2 cycles of treatment.

Results:

From August 2007 to March 2009, 45 patients were enrolled. The median age was 56 years (range: 22–75). Among the 40 patients evaluable for tumour response, one achieved a complete response, 22 had partial responses and 11 had stable disease. The overall response rates of the evaluable and intent-to-treat (ITT) populations were 58% (95% CI: 41–74%) and 53% (95% CI: 38–68%), respectively. The disease control rates in these populations were 85% (95% CI: 70–94%) and 82% (95% CI: 68–92%), respectively. In the ITT analysis, the median time to progression and overall survival were 6.8 and 13.9 months, respectively. Major grade 3–4 toxicities were neutropenia (51%), anaemia (22%), diarrhoea (16%), and infections (20%). No patient died of treatment-related toxicities.

Conclusion:

Concurrent weekly docetaxel and cisplatin plus oral tegafur/uracil and leucovorin are effective and well tolerated in the treatment of advanced gastric cancer.     

Phase II trial of cisplatin and gemcitabine in patients with advanced gastric cancer.

BACKGROUND: This phase II study was performed to determine the efficacy and toxicity of cisplatin and gemcitabine in patients with advanced gastric cancer. PATIENTS AND METHODS: Forty chemo-na?ve patients with measurable locoregionally advanced or metastatic gastric cancer were included; the median patient age was 53 years (range 35-71). Cisplatin was administered at a dose of 50 mg/m2, given in 1 h intravenously (i.v.) on days 1 and 8, followed after 24 h by gemcitabine at a dose of 800 mg/m2 given in 30 min i.v. on days 2, 9 and 16, every 28 days. RESULTS: A median number of four therapy cycles were given (range 2-8). Myelosuppresion was the most important toxicity. Grade 3-4 thrombopenia was observed in 19 patients (48%) and grade 3-4 leukopenia was observed in 23 (58%). Myelotoxicity was cumulative and caused omission of gemcitabine on day 16 in 55% of cycles. Non-haematological toxicity consisted mainly of grade 1-2 nausea and vomiting. Objective responses were observed in 30% of patients including two complete remissions and 10 partial remissions. Median survival was 11 months (range 3-27+). CONCLUSIONS: This cisplatin-gemcitabine regimen had moderate efficacy in patients with advanced gastric cancer, with manageable toxicity. Further studies with this combination may be warranted.     

Efficacy of oral tegafur modulation by uracil and leucovorin in advanced colorectal cancer. A phase II study

A phase II study was performed to assess the efficacy and toxicity of UFT (tegafur-uracil in the molar ratio 1: 4) modulated with leucovorin (LV) in previously untreated patients with advanced colorectal carcinoma (CRC). 79 patients with measurable advanced colorectal cancer (CRC) and no prior chemotherapy were included. 75 patients were evaluable for toxicity and response. The regimen consisted of LV 500 mg/m² administered intravenously on day 1, followed by oral UFT 390 mg/m² on days 1–14. Patients received oral LV 15 mg every 12 h on days 2–14. Treatment was repeated every 28 days for a minimum of four courses per patient. Three hundred and ninety-eight cycles of chemotherapy were delivered (median five per patient). 7 patients (9%) had a complete response, and 22 a partial response for an overall response rate of 39%. Mild gastrointestinal toxicity was dose limiting: grade 3–4 diarrhoea appeared in 9% of patients. Other grade 3–4 toxicities were nausea/vomiting and mucositis in 4% of patients, gastric pain and leucopenia in 3%. Oral UFT modulated by oral LV is active in advanced CRC and can be administered on an outpatient basis with no significant toxicity requiring hospitalisation. Given its excellent tolerance profile and low toxicity, the regimen should be thoroughly studied and compared with 5-fluorouracil modulated by LV.     

Phase II trial of oxaliplatin, leucovorin and fluorouracil in patients with advanced carcinoma of the esophagus.

BACKGROUND: The aim of the study was to evaluate the efficacy and tolerability of the combination of oxaliplatin, fluorouracil and leucovorin in patients with advanced esophagus cancer. PATIENTS AND METHODS: Thirty-five patients with recurrent or metastatic esophageal adenocarcinoma or squamous cell carcinoma were enrolled. Up to one prior chemotherapy regimen was allowed. All patients had bi-dimensionally measurable disease. Patients received oxaliplatin 85 mg/m2 as a 2-h infusion on day 1. Leucovorin (500 mg/m2) followed by fluorouracil bolus (400 mg/m2) and 22-h continuous infusion fluorouracil (600 mg/m2) was administered on days 1 and 2. Granulocyte colony stimulating factor was not routinely administered unless the patient developed febrile neutropenia or prolonged neutropenia. Treatment was repeated every 14 days. RESULTS: Of the thirty-five patients enrolled, all were evaluated for toxicity and 34 were evaluated for response. The overall response rate was 40% (95% confidence interval, 24% to 57%) with complete and partial response rates of 3% and 37%, respectively. The median response duration was 4.6 months, and the median overall survival was 7.1 months. One-year survival was 31%. The major toxicity noted was cumulative neutropenia, with 29% developing grade 4 toxicity. There was one treatment-related death secondary to neutropenic sepsis. The most common non-hematologic toxicity encountered with this regimen was cumulative peripheral neuropathy, with 26% experiencing grade 2 or 3 toxicity. CONCLUSIONS: The combination of oxaliplatin, leucovorin, and fluorouracil shows significant anti-tumor activity and a favorable toxicity profile in patients with metastatic carcinoma of the esophagus.     

Phase II trial of low-dose paclitaxel and cisplatin in patients with advanced gastric cancer

BACKGROUND: Paclitaxel has shown promising activity in gastric cancer and has synergism with cisplatin. This study was performed to evaluate the efficacy and toxicity of low-dose paclitaxel (145 mg/m(2)) plus cisplatin chemotherapy in metastatic or relapsed gastric cancer. METHODS: Chemotherapy-na?ve patients with metastatic or relapsed gastric cancer were enrolled. Paclitaxel 145 mg/m(2) was administered intravenously over 3 h, followed by cisplatin 60 mg/m(2) on Day 1 every 3 weeks in the outpatient setting. RESULTS: Of 39 patients enrolled, 17 (44%) had partial responses. Twelve (31%) had stable disease and eight (21%) progressive disease. Two patients (5%) were not evaluable because of early drop-out. The median time to progression was 4.7 months and the median overall survival was 12.1 months. The most common hematologic toxicity was anemia (41%). Grade 3/4 neutropenia and thrombocytopenia developed in 14 and 3%, respectively. The most common non-hematologic toxicities were peripheral neuropathy (43%) and emesis (43%). Grade 3/4 non-hematologic toxicities included emesis (11%), peripheral neuropathy (3%), diarrhea (3%) and hepatotoxicity (3%). CONCLUSIONS: Low-dose paclitaxel and cisplatin chemotherapy was active and well-tolerated in chemotherapy-na?ve gastric cancer patients. This regimen seems to have comparable efficacy to previously reported higher-dose paclitaxel plus cisplatin-containing regimens and fewer toxicities.     

Phase II trial of oxaliplatin and tegafur/uracil and oral folinic acid for advanced or metastatic colorectal cancer in elderly patients

OBJECTIVES: Colorectal cancer is usually diagnosed in elderly patients. Since there is clear evidence that such patients are under-treated and under-represented or even excluded from clinical studies and there are no reliable and prospective data on the feasibility and efficacy of an oxaliplatin (L-OHP)-based chemotherapy in this setting, we have tested the L-OHP plus oral uracil/tegafur (UFT) and oral folinic acid (FA) combination as first-line therapy in patients with advanced or metastatic colorectal cancer (MCRC) aged 70 or older. PATIENTS AND METHODS: Forty-seven patients with advanced or MCRC, aged over 70, were treated with L-OHP 65 mg/m(2) as an intravenous 3-hour infusion on day 1 and 8 plus UFT 300 mg/m(2) and FA 90 mg in 3 divided doses given orally on days 1-14 for each 3-week cycle. Patients were followed by a geriatric and a quality of life (QoL) assessment with specific scales and EORTC-QLQ-C30 questionnaire. RESULTS: All patients were assessable for toxicity and 45 for response to treatment. Complete response was achieved in 2 patients (4%) and partial response in 22 (47%) [overall response rate, 51%; 95% confidence interval (CI): 40.7-61.2%]; 18 patients (38%) had stable disease, and 5 (11%) had disease progression. The median duration of response was 8 months (range, 3-19+ months). After a minimum follow-up of 17 months, the median time to disease progression and the median overall survival were 8.0 (95% CI: 6.7-9.3%) and 14.1 (95% CI: 11.0-17.1%) months, respectively. Regimen safety was manageable. Most adverse events were mild to moderate, and this did not result in QoL impairment. The most common grade 3-4 treatment-related adverse events were diarrhea (17%), neutro- and thrombocytopenia (2%), laryngeal spasm (2%), and peripheral neuropathy (12.7%). No treatment-related deaths occurred. CONCLUSIONS: These results confirmed that this tested chemotherapy combination is active with acceptable tolerability and QoL maintenance in elderly patients with advanced or MCRC.     

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.     

Phase II study of oral eniluracil, 5-fluorouracil, and leucovorin in patients with advanced colorectal carcinoma

BACKGROUND: The oral administration of 5-fluorouracil (5-FU) is hindered by erratic bioavailability due to catabolism of 5-FU by the enzyme dihydropyrimidine dehydrogenase (DPD) in the gastrointestinal tract. Eniluracil is a potent inactivator of DPD which results in 100% oral bioavailability of 5-FU. Leucovorin (LV) is another biochemical modulator of 5-FU that potentiates inhibition of thymidylate synthase, the primary target of 5-FU. The goal of this study was to determine the antitumor activity and toxicity of an oral regimen containing eniluracil, 5-FU, and LV in patients with colorectal carcinoma. METHODS: Sixty eligible patients who had previously untreated, measurable, metastatic colorectal carcinoma were treated with oral eniluracil 50 mg on Days 1-7, 5-FU 20 mg/m(2) on Days 2-6, and LV 50 mg on Days 2-6. Cycles were repeated at 28-day intervals. RESULTS: The overall response rate was 13% (95% confidence interval [CI] = 6, 25%), with 1 complete response and 7 partial responses. Three additional patients had partial responses that were not confirmed at subsequent evaluations. The median time to progression of disease was 4.4 months (95% CI = 3.45, 7.69) and the median survival time was 12.6 months (95% CI = 9.1, 14.75). Grade 3-5 toxicity (1 toxic death) occurred in 51 patients (85%). Grade 4 neutropenia occurred in 25 patients (42%), and 18 patients (30%) had Grade 3-4 diarrhea. Twenty-one patients (35%) were hospitalized for toxicity, and 12 (20%) had febrile neutropenia. Baseline creatinine clearance was associated inversely with severe toxicity (P = 0.001). CONCLUSIONS: Although antitumor activity was observed, the frequent occurrence of severe toxicity with this regimen limited its clinical utility. Alternate schedules with a more favorable therapeutic index are undergoing clinical testing and should be pursued. The high level of toxicity observed with orally administered low dose 5-FU underscored the potency of eniluracil as a biochemical modulator.     

草酸铂、顺铂分别联用亚叶酸钙、替加氟治疗晚期胃癌的疗效观察

目的：观察国产草酸铂（OXA）、顺铂（DDP）分别联合亚叶酸钙（CF）、替加氟注射液（FT-207）组成方案治疗晚期胃癌的近期疗效和毒副反应。方法：40例病例按单纯随机抽样分成两组,治疗组21例,OXA130mg/m2静滴d1,CF 100？静滴d1-5,FT-207 600-800mg/m2静滴d1-5;对照组19例,DDP20mg/m2静滴d1-5,CF 100mg静滴d1-5,FT-207 600-800mg/m2静滴d1-5,两组均每3周重复,化疗两周期后评价疗效。结果：治疗组CR 2例（9.52%）、PR 9例（42.86%）、SD 7例（33.33%）、PD 3例（14.29%）,RR 11例（52.38%）;对照组CR 0例、PR 8例（42.11%）、SD 6例（28.57%）、PD 5例（26.32%）,RR 8例（42.11%）;中位生存期分别为10.8月、7.9月,两组一年生存率分别为47.62%、36.84%,上述经统计学处理无显著性差异,P〉0.05,不良反应两组主要表现为消化道反应、骨髓毒性和外周神经毒性,多在Ⅱ级以下,两组恶心、呕吐发生率各为28.57%、57.89%,经统计学处理有显著性差异,P〈0.05,外周神经毒性分别为14.29%、5.26%,治疗组稍高于对照组,其它副反应对照组均较治疗组高,但无统计学差异。结论：两组治疗晚期胃癌疗效相近,但治疗组毒副反应轻,病人易于接受。     

草酸铂、顺铂分别联用亚叶酸钙、替加氟治疗晚期胃癌的疗效观察

目的:观察国产草酸铂(OXA)、顺铂(DDP)分别联合亚叶酸钙(CF)、替加氟注射液(FT-207)组成方案治疗晚期胃癌的近期疗效和毒副反应。方法:40例病例按单纯随机抽样分成两组,治疗组21例,OXA130mg/m2静滴d1,CF 100?静滴d1-5,FT-207 600-800mg/m2静滴d1-5;对照组19例,DDP20mg/m2静滴d1-5,CF 100mg静滴d1-5,FT-207 600-800mg/m2静滴d1-5,两组均每3周重复,化疗两周期后评价疗效。结果:治疗组CR 2例(9.52%)、PR 9例(42.86%)、SD 7例(33.33%)、PD 3例(14.29%),RR 11例(52.38%);对照组CR 0例、PR 8例(42.11%)、SD 6例(28.57%)、PD 5例(26.32%),RR 8例(42.11%);中位生存期分别为10.8月、7.9月,两组一年生存率分别为47.62%、36.84%,上述经统计学处理无显著性差异,P>0.05,不良反应两组主要表现为消化道反应、骨髓毒性和外周神经毒性,多在Ⅱ级以下,两组恶心、呕吐发生率各为28.57%、57.89%,经统计学处理有显著性差异,P<0.05,外周神经毒性分别为14.29%、5.26%,治疗组稍高于对照组,其它副反应对照组均较治疗组高,但无统计学差异。结论:两组治疗晚期胃癌疗效相近,但治疗组毒副反应轻,病人易于接受。     

多西他赛对比表柔比星联合顺铂、亚叶酸钙和氟尿嘧啶一线治疗进展期胃癌的随机对照研究

目的　研究多西他赛（ＴＸＴ）对比表柔比星（ＥＰＩ）联合顺铂（ＤＤＰ）、亚叶酸钙（ＬＶ）、氟尿嘧啶（５-ＦＵ）持续滴注一线治疗进展期胃癌的疗效和不良反应。方法　２００５年１月至２００７年１月,６４例进展期胃癌住院患者按随机数字表随机分为ＤＣＦ方案组和ＥＣＦ方案组各３２例。ＤＣＦ方案组给予ＴＸＴ、ＤＤＰ、ＬＶ联合低剂量５-ＦＵ持续静脉滴注化疗;ＥＣＦ组给予ＥＰＩ、ＤＤＰ、ＬＶ联合低剂量５-ＦＵ持续静脉滴注化疗,２１天为１周期。至少完成２个周期化疗后评价两组的有效率、不良反应、疾病进展时间（ＴＴＰ）和总生存时间（ＯＳ）。结果　两组患者均可评价疗效。ＤＣＦ方案组总有效率（ＯＲＲ）为５６.３％,ＥＣＦ方案组为２８.１％,两组差异有统计学意义（Ｐ＝０.０２３）;在ＴＴＰ和ＯＳ方面ＤＣＦ方案组均优于ＥＣＦ方案组（P＜０.０５）。除过敏反应外,两组患者的不良反应均无统计学意义（Ｐ＞０.０５）,两组均无３～４级过敏反应发生。结论　三周方案ＴＸＴ、ＤＤＰ和ＬＶ联合低剂量５-ＦＵ静脉持续滴注治疗进展期胃癌疗效优于ＥＣＦ方案,不良反应相似,值得进一步推广。     

A phase II study of epirubicin, cisplatin and uracil-tegafur for advanced gastric carcinoma

BACKGROUND: Due to its greater convenience, a combination of uracil and tegafur (referred to as UFT) taken orally is an attractive alternative to continuous intravenous (i.v.) 5-fluorouracil (5-FU) infusion. This phase II study assessed the response rate and toxicity profile of the combination of epirubicin, cisplatin and UFT in patients with metastatic adenocarcinoma of the stomach. METHODS: Epirubicin (50 mg/m(2)) and cisplatin (60 mg/m(2)) were administered i.v. to 35 patients with metastatic gastric carcinoma on day 1, and subsequently UFT (300 mg/m(2)/day) was administered orally in divided doses for 21 days. The treatment was repeated every 3 weeks. The response rate, time to disease progression, survival and toxic effects were analyzed. RESULTS: Thirty-two of the 35 enrolled patients were assessed subsequently for response. The median number of cycles was four. Thirteen patients (40.6%) showed partial responses, while none showed a complete response. The median time to progression of carcinoma was 20.4 weeks, and the median survival was 37 weeks. Grade 3 and 4 neutropenia was observed in 25% of patients. Grade 3 nausea and vomiting was observed in 28% of patients. No treatment-related death was observed. All patients received doses as planned, except for one who required a 75% dose reduction due to nephrotoxicity. Six of 132 cycles were delayed >7 days after four cycles. CONCLUSIONS: The combination of epirubicin, cisplatin and UFT showed anticancer activity against metastatic gastric adenocarcinoma, had a tolerable toxicity profile and showed excellent patient compliance.     

Phase I study of preoperative oral uracil and tegafur plus leucovorin and radiation therapy in rectal cancer.

PURPOSE: Preoperative combined-modality therapy for rectal cancer may allow for sphincter preservation, while decreasing recurrence rates and improving the overall prognosis. Oral chemotherapy with uracil and tegafur (UFT) plus leucovorin (LV) may reduce costs and complications associated with protracted infusions of fluorouracil. Our goal was to evaluate the safety of UFT plus LV combined with preoperative radiation and determine the maximum-tolerated dose (MTD) and dose-limiting toxicity (DLT) of UFT plus LV in this setting. PATIENTS AND METHODS: Patients with tumor-node-metastasis stage II or III rectal cancer received escalating doses of UFT (starting at 250mg/m(2)/d, with 50-mg/m(2)/d increments between consecutive cohorts) and fixed doses of LV (90 mg/d). The UFT and LV combination was given 5 days per week concurrently with a 5-week course of preoperative radiation totaling 45 Gy (1.8 Gy/fraction). Surgery was performed 4 to 6 weeks after radiation and was followed by four 35-day cycles of fixed doses of UFT and LV (28 days of therapy each cycle). RESULTS: Fifteen patients were treated, and 13 received the full preoperative chemotherapy. All planned radiation was delivered successfully. The MTD of UFT with radiation was 350 mg/m(2)/d with 90 mg/d of LV. Diarrhea was the DLT. Sphincter-preserving surgery was performed in 12 of 14 patients. One patient had progressive disease before surgery. Pathologic evaluation of 14 resected specimens showed a complete response in three cases. CONCLUSION: Preoperative chemoradiation with oral UFT plus LV is feasible and well tolerated and should be further investigated.     

Preoperative chemoradiotherapy for rectal cancer: randomized trial comparing oral uracil and tegafur and oral leucovorin vs. intravenous 5-fluorouracil and leucovorin

PURPOSE: To compare, in a randomized trial, 5-fluorouracil (FU) plus leucovorin (LV) (FU+LV) vs. oral uracil and tegafur (UFT) plus LV (UFT+LV) given concomitantly with preoperative irradiation in patients with cT3-4 or N+ rectal cancer. METHODS AND MATERIALS: A total of 155 patients were entered onto the trial. Patients received pelvic radiotherapy (4500-5,040 cGy in 5 to 6 weeks) and chemotherapy consisting of two 5-day courses of 20 mg/m(2)/d LV and 350 mg/m(2)/d FU in the first and fifth weeks of radiotherapy (77 patients) or one course of 25 mg/d oral LV and 300 mg/m(2)/d UFT for 4 weeks beginning in the second week of radiotherapy (78 patients). The primary endpoints were pathologic complete response (pCR) and resectability rate. Secondary endpoints included downstaging rate, toxicity, and survival. RESULTS: Grade 3-5 acute hematologic toxicity occurred only with FU+LV (leukopenia 9%; p = 0.02). There were no differences in resectability rates (92.1% vs. 93.4%; p = 0.82). The pCR rate was 13.2% in both arms. Tumor downstaging was more frequent with UFT+LV (59.2% vs. 43.3%; p = 0.04). Three-year overall survival was 87% with FU+LV and 74% with UFT+LV (p = 0.37). The 3-year cumulative incidences of local recurrence were 7.5% and 8.9%, respectively (p = 0.619; relative risk, 1.46; 95% confidence interval 0.32-6.55). CONCLUSION: Although this study lacked statistical power to exclude clinically significant differences between both groups, the outcome of patients treated with UFT+LV did not differ significantly from that of patients treated with FU+LV, and hematologic toxicity was significantly lower in the experimental arm.     

Phase II trial of 5-fluorouracil, leucovorin and cisplatin for treatment of advanced pancreatic adenocarcinoma

Background. Advanced pancreatic adenocarcinoma is a rapidlyfatal disease for which an active chemotherapy regimen is sought.Here we report the outcome of a phase II trial to assess thetoxicity and efficacy of a combination of 5-flu-orouracil (5-FU),leucovorin and cisplatin (CDDP). Methods. A regimen combining leucovorin (200 mg/m²/d x 5d),5-FU (375 mg/m²/d x 5d in a 2-hour infusion) and CDDP (15 mg/m²/dx 5d) was given to 52 patients with histologically-proven, previouslyuntreated, locally advanced (n = 13) and/or metastatic (n =39) pancreatic adenocarcinoma. Results. Of 48 patients evaluable for response, 10 achievedpartial responses, for an overall response rate of 21% (95%CI 9.5%–32.5%), and a palliative effect was observed in52%. The median survival was 9.5 months (18 months for locally-advancedand 5 months for metastatic disease) with a 1-year survivalof 34.6% and a median progression-free survival of 4.5 months.Chemotherapy was well tolerated with grades 3 or 4 nausea/vomitingin 12%, diarrhea in 6%, anaemia in 17%, neutropenia in 12%,and thrombocytopenia in 10%. Eleven patients (21%) had Grade2 peripheral neuropathy. Conclusion. The combination of leucovorin, 5-FU and CDDP seemsto be an effective palliative treatment, with moderate toxiceffects, in advanced pancreatic adenocarcinoma. advanced pancreatic adenocarcinoma, cisplatin, 5-fluorouracil, leucovorin