Docetaxel (Taxotere), cisplatin, UFT, and leucovorin combination chemotherapy in advanced gastric cancer

We conducted this study to ascertain the efficacy and toxicity of docetaxel and cisplatin combined with oral UFT and leucovorin as a first-line treatment for patients with advanced gastric cancer. In all, 52 patients received courses of docetaxel 60 mg m(-2) intravenously (i.v.) for 1 h and then cisplatin 75 mg m(-2) i.v. for 2 h on day 1. Oral UFT at 400-600 mg day(-1), as determined by body surface area, and leucovorin at 75 mg day(-1) were administered for 21 consecutive days from day 1, and this was followed by a 7-day drug-free interval. A total of 225 courses were administered, and the median number of courses per patient was four. Four complete responses (7.7%) and 22 partial responses (42.3%) were achieved, giving an overall response rate of 50% (95% Confidence Interval: 36.4-63.6%). The major toxicity was neutropenia, which reached grade 3/4 in 36 patients (69.3%). Grade 3/4 nausea and vomiting was observed in 12 patients (23.1%). Median time to progression was 22 weeks (4 to 156+ weeks), median survival duration was 48 weeks (4 to 156+ weeks), and median response duration was 24 weeks (6-152 weeks). We conclude that docetaxel, cisplatin, oral UFT, and leucovorin combination chemotherapy is effective and tolerable for the treatment of advanced gastric cancer.     

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.     

大剂量顺铂联合环磷酰胺、平阳霉素治疗食管癌22例

我们采用大剂量顺铂联合化疗治疗晚期食管癌２２例。化疗方案为ＰＣＰ（ＤＤＰ＋ＣＴＸ＋ＰＹＭ）。顺铂剂量为１００ｍｇ／ｍ￣２，一次给药，同时水化、利尿。本组病的完全缓解３例，部分缓解７例，总有效率（ＣＲ＋ＰＲ）４６％、中位缓解期５个月。化疗的毒副作用有骨髓抑制、消化道反应、脱发、发烧，而肝肾心神经系统毒性反应较轻。     

An open, multi-centre, phase II clinical trial to evaluate the efficacy and safety of paclitaxel, UFT, and leucovorin in patients with advanced gastric cancer

The aim of the study was to evaluate the response rate and safety of weekly paclitaxel (Taxol((R))) combination chemotherapy with UFT (tegafur, an oral 5-fluorouracil prodrug, and uracil at a 1 : 4 molar ratio) and leucovorin (LV) in patients with advanced gastric cancer. Patients with histologically confirmed, locally advanced or recurrent/metastatic gastric cancer were studied. Paclitaxel 1-h infusion at a dose of 100 mg m(-2) on days 1 and 8 and oral UFT 300 mg m(-2) day(-1) plus LV 90 mg day(-1) were given starting from day 1 for 14 days, followed by a 7-day period without treatment. Treatment was repeated every 21 days. From February 2003 to October 2004, 55 patients were enrolled. The median age was 62 years (range: 32-82). Among the 48 patients evaluated for tumour response, two achieved a complete response and 22 a partial response, with an overall response rate of 50% (95% confidence interval: 35-65%). All 55 patients were evaluated for survival and toxicities. Median time to progression and overall survival were 4.4 and 9.8 months, respectively. Major grade 3-4 toxicities were neutropenia in 25 patients (45%) and diarrhoea in eight patients (15%). Although treatment was discontinued owing to treatment-related toxicities in nine patients (16%), there was no treatment-related mortality. Weekly paclitaxel plus oral UFT/LV is effective, convenient, and well tolerated in treating patients with advanced gastric cancer.     

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 study of UFT with leucovorin and irinotecan (TEGAFIRI): first-line therapy for metastatic colorectal cancer

This phase II trial was performed to evaluate the efficacy and tolerability of oral tegafur-uracil (UFT) with leucovorin (LV) combined with intravenous (i.v.) irinotecan every 3 weeks (TEGAFIRI) as first-line treatment for patients with metastatic colorectal cancer (mCRC). Patients received oral UFT 250 mg m(-2) day(-1) and LV 90 mg day(-1) in three divided daily doses for 14 days followed by a 1-week rest and i.v. irinotecan 250 mg m(-2) as a 90-min infusion every 3 weeks. Tumour responses, assessed every two cycles using RECIST criteria, were reviewed by an independent review committee. In 52 evaluable patients, the best overall response rate was 33% (95% confidence intervals (CI) 20-47%; 1 complete and 16 partial responses). The median time to progression was 5.4 months (95% CI 3.02-7.52 months) and median overall survival was 14.9 months (11.73-17.97 months). A total of 307 cycles were administered, with a median number of five cycles per patient (range: 1-10). The most common grade 3/4 toxicities were neutropenia (25% of patients), diarrhoea (22%), vomiting (11%) and anaemia (11%). The TEGAFIRI regimen is a feasible, well-tolerated and convenient treatment option for patients with non-resectable mCRC.     

Epirubicin, cisplatin and docetaxel combination therapy for metastatic gastric cancer.

BACKGROUND: Docetaxel is a new agent with activity in metastatic gastric cancer. This phase II study was designed to evaluate the activity and safety of an epirubicin, cisplatin and docetaxel combination in patients with this disease. PATIENTS AND METHODS: Forty-six patients with gastric adenocarcinoma with measurable distant metastasis were eligible for the study. Patients received epirubicin 50 mg/m(2) and docetaxel 60 mg/m(2), on day 1, and cisplatin 60 mg/m(2) on day 2. Granulocyte colony-stimulating factor 300 mug/day subcutaneously was given on days 5 and 6. Cycles were repeated every 3 weeks for a maximum of eight courses. RESULTS: All patients were evaluable for response and toxicity. Two complete and 21 partial responses were observed, with an overall response rate of 50% [95% confidence interval (CI) 36% to 64%]. Stable disease was observed in 13 patients (28%) and progressive disease in 10 patients (22%). The median time to progression was 6 months (95% CI 5-7) and the median overall survival was 11.2 months (95% CI 8.5-13.9). Grade 3/4 neutropenia, thrombocytopenia and anemia occurred in 46%, 7% and 13% of patients, respectively. There were five episodes of febrile neutropenia in four patients. Other grade 3 toxicities included mucositis in three patients (6.5%), vomiting in four patients (8.7%) and diarrhea in one patient (2%). There were no cardiac toxicity, severe neurotoxicity or treatment-related deaths. CONCLUSIONS: The epirubicin, cisplatin and docetaxel combination is an active and well tolerated novel chemotherapy regimen for treating metastatic gastric cancer and deserves further evaluation in randomized studies.     

多西他赛联合顺铂、氟尿嘧啶和亚叶酸的新辅助化疗方案治疗不能切除进展期胃癌的疗效观察

背景与目的：手术治疗目前仍是无远处转移胃癌的标准治疗方法，但大多数胃癌患者就诊时已经是进展期而不宜手术。新辅助化疗足指在外科手术术前给予化疗，其目的之一是通过缩小原发肿瘤使之可以进行手术切除，最终延长生存期。本临床试验目的在于研究多西他赛（商品名：泰索帝）联合顺铂、氟尿嘧啶和亚叶酸给药方案术前进行诱导化疗对不能切除的进展期胃癌的临床疗效及毒副反应。方法：入组患者均为本院2003年6月-2005年6月收治的12例晚期胃癌而无法行根治手术者。术前的新辅助化疗方案为：泰索帝75mg／m^2、顺铂75mg/m^2。第1天；氟尿嘧啶500mg／m^2、亚叶酸200mg／m^2第1～5天，每三周为一个周期，共两个周期。观察新辅助化疗后原发病灶的变化情况并观察用药后的毒副反应。结果：新辅助化疗后9例患者获得肿瘤减期，疗程结束后4～6周8例进行根治性手术切除。临床完全缓解（CR）1例，部分缓解（PR）8例，无变化（NC）3例，进展（PD）0例，有效率75％（9／12），腹水消退率63.6％（7／11）。组织学效果：轻度有效3例，中度有效4例，显著有效1例。副反应主要为骨髓抑制、腹泻、恶心呕吐、脱发，经对症以及营养支持治疗后均能缓解。结论：多西他赛加顺铂、氟尿嘧啶及亚叶酸的新辅助化疗方案在高度进展期胃癌的治疗中，对提高手术切除率疗效显著，耐受性良好。     

表柔比星、亚叶酸钙、氟尿嘧啶与顺铂联合化疗方案(ECF-L)治疗晚期胃癌的化疗与安全性临床研究

目的：评价表柔比星、氟尿嘧啶、亚叶酸钙以及顺铂(ECF—L)联合化疗方案对无法手术切除或术后复发的晚期胃癌的疗效与安全性。方法：本研究入选对象为经病理学证实的具有至少一个可测量病灶的原发性或转移至其他部位的无法手术切除的胃癌患者。所用化疗方案为：表柔比星50mg／m^2第一天，亚叶酸钙200mg／m^2第1—3天，氟尿嘧啶600mg／m^2第1—3天，以及顺铂20mg／m^2第1-3天静脉给药。3周为1周期，3个周期为一次疗程。治疗过程中允许必要的支持治疗。结果：2000年3月—2001年8月期间，各院共有79例患者入选并接受化疗(16例为Ⅲ期，63例为Ⅳ期；37例为初治患者，42例为复治患者；53例为术后复发患者)。最终66例患者可以评价疗效，其中CR4例、PR18例，总缓解率为33．3％(22／66)；初治患者缓解率为36．7％(11／30)，复治患者缓解率为30．6％(11／36)，具有淋巴软组织转移的患者其缓解率为50．0％(15／30)。除缓解病例外，NC患者25例，PD患者19例，以及治疗过程中出组患者13例(出组率16．4％，13／79)。化疗过程中发生的毒副反应(WH0标准)Ⅲ度-Ⅳ度主要为骨髓抑制20．1％、脱发5．1％和恶心、呕吐2．3％。结论：本研究提示ECF—L方案可以安全地用于治疗手术无法切除的晚期胃癌患者。     

Phase II study of UFT and oxaliplatin in first-line treatment of advanced colorectal cancer

The purpose of this study was to evaluate the efficacy, assessed as response rate, and toxicity of UFT (Tegafur-Uracil) in combination with oxaliplatin as first-line treatment of advanced colorectal cancer (CRC). In all, 84 patients with recurrent or metastatic CRC with measurable disease were included. Treatment consisted of oxaliplatin 85 mg m(-2) in 120-min intravenous (i.v.) infusion on days 1 and 15; i.v. l,leucovorin (l,LV) 250 mg m(-2) given in 2 h on day 1, followed by oral UFT 390 mg m(-2) on days 1-14, and oral l,LV 7.5 mg/12 h on days 2-14. Cycles were repeated every 28 days. A total of 492 cycles of chemotherapy were delivered with a median of six per patient (range 1-12). There was one complete response (1%) and 28 partial responses (34%) for an overall response rate of 35% (95% confidence interval (CI): 24-46%). A total of 36 patients (44%) had stable disease, whereas 17 (21%) had a progression. The median time to progression was 7.3 months and the median overall survival was 16.8 months. A prescheduled preliminary analysis was performed after inclusion of 16 patients who detected a high gastrointestinal toxicity, which led to a reduction of the UFT dose to 300 mg m(-2). With this new dosage, grade 3-4 diarrhoea and grade 3-4 nausea/vomiting dropped to 21 and 14% of patients, respectively. Other grade 3-4 toxicities were stomatitis in one (1%), anaemia in three (5%), neutropenia in two (3%), thrombocytopenia in one(1%), fatigue in six (9%), peripheral sensory neuropathy in nine (14%) and laryngopharyngeal dysesthesia in two patients (2%). The combination of oxaliplatin and UFT-l,LV is an active, easy-to-administer regimen with moderate toxicity. Hence, this regimen is worthy of further investigation.     

Epirubicin, cisplatin and oral UFT with leucovorin (''ECU''): a phase I-II study in patients with advanced upper gastrointestinal tract cancer.

Background: ECF (epirubicin, cisplatin, protracted venous fluorouracil) is superior to FAMTX in gastroesophageal cancer, but protracted fluorouracil adds to its morbidity and cost. In this dose-escalation pilot study, fluorouracil was replaced by oral UFT and leucovorin.Patients and methods: Thirty unpretreated patients with advanced upper gastrointestinal cancers received epirubicin 50 mg/m² and cisplatin 60 mg/m² i.v. on day 1, and leucovorin 45 mg p.o. on days 1, 8 and 15, of a 21-day cycle for up to 8 cycles. UFT was taken 12-hourly throughout, at escalating doses in four cohorts ranging from 150–325 mg/m² per day.Results: The maximum tolerable dose of UFT, recommended for further study, was 200 mg/m² per day. At higher doses, more than two-thirds patients required dose reductions, although mostly for persistent mild (CTC grade 2) nausea, diarrhoea or fatigue, rather than for severe acute toxicity. Myelotoxicity was mild. Twenty patients, including 15 with gastroesophageal cancer, had assessable disease. Among these there were nine WHO objective responses, all in gastroesophageal patients, including two radiological complete responses.Conclusions: ECU is well tolerated at the defined dose, with activity comparable to ECF in gastroesophageal cancer. UFT and other oral 5FU dosing strategies make promising components of combination chemotherapy, deserving further, randomised evaluation.     

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。     

A phase I study of combination chemotherapy with gemcitabine and oral UFT for advanced non-small cell lung cancer

A phase I study was carried out to determine the optimal dose and administration schedule for combined UFT plus gemcitabine therapy in patients with non-small cell lung cancer. Twenty-four patients (including 11 patients previously treated with cisplatin as the key drug) received oral UFT 400 mg x m(-2) on days 1 to 14 with intravenous infusions of gemcitabine (800 mg x m(-2) on days 8 and 15, or 900 mg x m(-2) on days 8 and 15, or 900 mg x m(-2) on days 1, 8 and 15). The most appropriate dosing option appeared to be 400 mg x m(-2) per day of oral UFT for 14 consecutive days with 900 mg x m(-2) gemcitabine on days 8 and 15. Eight of the 24 patients achieved partial response. The combination chemotherapy UFT and gemcitabine was well tolerated and may benefit patients with advanced non-small cell lung cancer. A multicentre phase II study using a 3-weekly regimen is in progress.     

Phase I trial of Orzel (UFT plus leucovorin), cisplatin, and radiotherapy in the treatment of potentially resectable esophageal cancer

PURPOSE: Fluorinated pyrimidines have been established as radiosensitizers in the combined modality therapy of esophageal cancer. UFT, an oral combination of a 5-fluorouracil pro-drug (uracil) and a dihydropyrimidine dehydrogenase inhibitor (ftorafur), may provide improvement in the ease of administration with equal efficacy. This Phase I study was designed to determine the maximal tolerated dose and dose-limiting toxicity of UFT, leucovorin, and cisplatin when given with radiotherapy in the neoadjuvant treatment of resectable esophageal cancer. METHODS: Chemotherapy consisted of i.v. cisplatin 80 mg/m(2) (Days 1 and 22) and UFT with leucovorin orally on Days 1-35. UFT was escalated in 50-mg/m(2) increments, starting at 200 mg/m(2)/d. Radiotherapy consisted of 4500 cGy in 25 fractions. Patients underwent resection 4-6 weeks after chemoradiotherapy. RESULTS: Ten patients with resectable esophageal cancer were enrolled. Of the 7 patients entered at dose level 1, 1 developed a dose-limiting toxicity of nausea. All 3 patients entered at dose level 2 developed dose-limiting toxicity. The maximal tolerated dose for UFT was the starting level, 200 mg/m(2)/d. Of the 10 patients enrolled, 8 underwent esophagectomy and 2 developed progressive disease and did not undergo surgery. The disease of 6 of the 8 patients was downstaged at surgery. CONCLUSION: The recommended UFT dose for Phase II studies is 200 mg/m(2)/d given orally in two divided doses when given with leucovorin, cisplatin, and radiotherapy.     

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。     

多西紫杉醇联合顺铂治疗蒽环类耐药的晚期乳腺癌

Objective： To observe the effect and toxicity of docetaxel with cisplatin in anthracyclines-resistant advanced breast cancer. Methods： Forty-five female patients received docetaxel 60 mg/m^2 on dl and cisplatin 30 mg/m^2 on d1-d3 of every 28 days. Every patient was treated with at least 2 cycles and a median of 3 cycles （2-6 cycles ）. Results： Five patients achieved complete response （11.1%） and 18 partial response （40.0%）, 10 stable disease （22.2%）. The overall response rate was 51.1%. The clinical disease control rate was 73.3%, median time to tumor progression （TTP） was 7.8 months （1.0-34.5 months）, median survival time was 17.6 months （range 1.9-48.0 months）, and one year survival rate was 65.2%. The main side effect was marrow suppression. The treatment was well tolerated with grades Ⅲ and Ⅳ leukopenia in nine （20%） and ten （22.2%） patients. Conclusion： Combinative chemotherapy of docetaxel and cisplatin has a good anti-tumor activity on refractory advanced breast cancer with manageable toxicity.     

A phase 2 study of a fixed combination of uracil and ftorafur (UFT) and leucovorin given orally in a 3‐times‐daily regimen to treat patients with recurrent metastatic breast cancer

BACKGROUND:

A combination of uracil and ftorafur (UFT) was developed to combine the cytotoxic effects of 5‐fluorouracil (5‐FU) with convenient oral dosing. Leucovorin was combined with UFT to further potentiate the effect of 5‐FU on tumor cells. Orally administered UFT and leucovorin provided higher peak plasma concentrations of 5‐FU and prolonged therapeutic 5‐FU concentrations compared with continuous infusion of 5‐FU.

METHODS:

Ninety‐one patients with metastatic breast cancer who had been previously treated with anthracyclines and/or taxanes were treated with UFT and leucovorin, given orally, for the first 28 days of a 35‐day cycle. The total daily dose of UFT was 300 mg/m², administered in 3 doses of 100 mg/m² each every 8 hours. The primary endpoint was time to disease progression (TTP). Secondary objectives included overall tumor response rate (overall response equals complete response plus partial response) and overall survival.

RESULTS:

Of the 91 patients enrolled, 70 were evaluable for efficacy. Although no complete responses were observed, 7 patients had partial responses, for an overall response rate of 10% in the evaluable population. The median TTP for the evaluable population was 10 weeks, and the proportion of patients who were free of disease progression at 6 months was 23%. The median overall survival was 59.4 weeks for all patients enrolled. Common, drug‐related ≥ grade 3 adverse events (graded according to National Cancer Institute Common Toxicity Criteria, version 2) included diarrhea, vomiting, abdominal pain, and nausea.

CONCLUSIONS:

The combination of UFT and leucovorin administered orally in a 3‐times‐daily regimen was found to have modest activity. Grade 3 toxicities were manageable with appropriate dose adjustments in patients with metastatic breast cancer previously treated with anthracyclines and/or taxanes. Cancer 2010. © 2010 American Cancer Society.     

A phase I study of UFT/leucovorin, carboplatin, and paclitaxel in combination with external beam radiation therapy for advanced esophageal carcinoma

PURPOSE: Concurrent chemotherapy and radiation therapy (RT) are used to treat patients with esophageal cancer. The optimal combination of chemotherapeutic agents with RT is not well established. We evaluated the safety and preliminary efficacy of a combination of UFT/leucovorin, carboplatin, and paclitaxel with RT in a Phase I study of patients with advanced esophageal cancer. METHODS AND MATERIALS: Patients with squamous cell carcinoma or adenocarcinoma of the esophagus initially received UFT/leucovorin, carboplatin, and paclitaxel with RT (1.8 Gy daily to 45 Gy). After completion, the disease was restaged and patients were evaluated for surgery. Primary end points included determination of dose-limiting toxicities (DLTs) and a recommended Phase II dose. Secondary objectives included determination of non-DLTs, as well as preliminary radiographic and pathologic response rates. RESULTS: Twelve patients were enrolled (11 men, 1 woman). All were assessable for toxicity and efficacy. One of 6 patients at Dose Level 1 (UFT/leucovorin, 200/30 mg twice daily on RT days; carboplatin, area under the curve [AUC] 5, Weeks 1 and 4; paclitaxel, 175 mg/m2 Weeks 1 and 4) had a DLT (febrile neutropenia). Of these 6 patients, 4 underwent esophagectomy and none achieved a pathologic complete response. Six patients were then enrolled at Dose Level 2 (UFT/leucovorin, 300/30 mg in the morning and 200/30 mg in the evening on RT days; carboplatin, AUC 5, Weeks 1 and 4; paclitaxel, 175 mg/m2 Weeks 1 and 4). Two of 6 patients at Dose Level 2 developed DLTs (febrile neutropenia in both). Esophagectomy was performed in 3 patients, with 2 achieving a pathologic complete response. CONCLUSIONS: Maximum tolerated doses in this study were UFT/leucovorin, 200/30 mg twice daily on RT days; carboplatin, AUC 5, Weeks 1 and 4; and paclitaxel, 175 mg/m2 Weeks 1 and 4 when delivered with external RT. In this small study, this regimen appears active, but toxic.     

Treatment of unresectable, locally advanced pancreatic adenocarcinoma with combined radiochemotherapy with 5-fluorouracil, leucovorin and cisplatin

Although clinical response to primary chemotherapy in stage II and III breast cancer is associated with a survival advantage, it is the degree of pathological response in the breast and ipsilateral axilla that best identifies patients with a good long-term outcome. A mathematical model of the initial response of 39 locally advanced tumours to anthracycline-based primary chemotherapy has been previously shown to predict subsequent clinical tumour size. This model allows for the possibility of primary resistant disease, the presence of which should therefore be associated with a worse outcome. This study reports the application of this model to an additional five patients with locally advanced breast cancer, as well as to 63 patients with operable breast cancer, and confirms the biological reality of the model parameters for these 100 breast cancers treated with primary anthracycline-based chemotherapy. The tumours that responded to chemotherapy had higher cell-kill (P < 0.0005), lower resistance (P < 0.0001) and slower tumour regrowth (P < 0.002). Furthermore, ER-negative tumours had higher cell-kill (P < 0.05), as compared with ER-positive tumours. All patients with a pathological complete response had zero resistance according to the model. Furthermore, the long-term implication of chemo-resistant disease was demonstrated by survival analysis of these two groups of patients. At a median follow-up of 3.7 years, there was a statistically significantly worse survival for the 37 patients with locally advanced breast cancer identified by the model to have more than 8% primary resistant tumour (P < 0.003). The specificity of this putative prognostic indicator was confirmed in the 63 patients presenting with operable disease where, at a median follow-up of 7.7 years, those women with a resistant fraction of greater than 8% had a significantly worse survival (P < 0.05). Application of this model to patients treated with neoadjuvant chemotherapy may allow earlier identification of clinically significant resistance and permit intervention with alternative non-cross-resistant therapies such as taxoids.     

健择联合顺铂合并放疗治疗进展期食管癌的临床研究

对41例初治进展期食管癌患者采用健择联合顺铂合并放射治疗。38例患者可以评估疗效和毒性。健择1000mg/m2,静脉滴入,d1、d8;顺铂20mg/m2,静脉滴入,d1~d4;同时合并放射治疗,每次2Gy,每周5次,共5周,总剂量为50Gy;化疗周期每21或28d重复。结果5例患者完全缓解,17例患者部分缓解,总有效率为58%;27例患者吞咽困难缓解,缓解率为71%;中位生存期为11·3个月;1、2年生存率分别为63%和45%;最常见的3、4度毒性是血小板下降(29%)、贫血(21%)、白细胞下降(24%)和食道炎(21%);无治疗相关死亡和3、4度的神经毒性。初步研究结果提示,健择加顺铂合并放疗方案治疗进展期食管癌耐受性好,疗效显著,值得临床广泛推广应用。