Bimonthly high-dose leucovorin, 5-fluorouracil infusion and oxaliplatin (FOLFOX3) for metastatic colorectal cancer resistant to the same leucovorin and 5-fluorouracil regimen

Background: FOLFOX2, a bimonthly regimen of high-dose leucovorin (LV), 48-hour continuous infusion of 5-fluorouracil (5-FU) (LV–5-FU) and oxaliplatin (100 mg/m2) produced a high response rate (46%; 95% confidence interval (95% CI): 31%–60%) in 5-FU pre-treated patients with metastatic colorectal cancer. In this phase II study, pre-treated patients were given a lower dose of oxaliplatin to reduce the toxic effects of the regimen.Patients and methods: Thirty patients with advanced colorectal adenocarcinoma and progression while receiving bimonthly LV–5-FU (LV: 500 mg/m2, 5-FU: 1.5–2 g /m2/ 22 hours, days 1–2, every two weeks), were given the same LV–5-FU schedule with the addition of oxaliplatin (85 mg/m2) every two weeks (FOLFOX3).Results: The main toxic effects were peripheral neuropathy (90%) with four severe sensitive neuropathies (WHO grade 2: 13%). The response rate was 20% (95% CI: 8%–39%). Median progression-free survival was 26 weeks, median survival was 57 weeks from the start of FOLFOX3 and median duration of the response was 37 weeks.Conclusions: Results obtained with FOLFOX3 confirmed the synergy between oxaliplatin and 5-FU in 5-FU-resistant metastatic colorectal cancer. However, the response rate seems to be lower than that obtained with FOLFOX2. Further studies to determine the best oxaliplatin dose intensity are in progress.     

奥沙利铂联合表柔吡星和5-Fu治疗晚期胃癌疗效和安全性研究

目的REAL2研究中使用奥沙利铂的EOF方案由于较好的疗效和安全性获得了广泛关注,但中国胃癌患者对REAL2研究中的三药联合EOF方案耐受性较差,本研究使用了改良的EOF方案,将氟尿嘧啶（5-Fu）由原来的静脉输注21天改为5天,观察奥沙利铂联合5-Fu／LV、表柔吡星治疗晚期胃癌的疗效及不良反应。方法30例晚期胃癌患者,初治19例,复治11例。表柔吡星50mg／m^2静脉注射d1,奥沙利铂130mg／m^2静脉滴注2小时d1,5-Fu375～425mg／（m^2·d）d1～5静脉持续输注120小时,每3周重复,每化疗2个疗程评价1次疗效。结果30例患者中,总缓解率43．33％,完全缓解1例,部分缓解12例。初治病例缓解率52．63％（10／19）,略高于REAL2研究中标准EOF方案的42．4％缓解率,复治病例缓解率27．33％（3／11）。KPS评分提高10分以上者10例（33．33％）。在治疗中,主要的Ⅲ～Ⅳ度不良反应为：中性粒细胞减少33．3％（10／30）,血小板减少10％（3／30）,贫血13．33％（4／30）,恶心呕吐23．33％（7／30）．RE．A12研究中标准EOF方案的Ⅲ～Ⅳ度中性粒细胞减少29．9％,与本研究类似,标准EOF方案中的Ⅲ～Ⅳ度血小板减少4．3％,贫血6．5％,恶心呕吐13．8％,略低于本研究,但在本研究中没有观察到Ⅲ～Ⅳ度发热性中性粒细胞减少及血栓栓塞等严重不良反应,而REAL2研究中,发热性中性粒细胞减少和血栓栓塞均为8．5％。结论奥沙利铂联合5-Fu及表柔吡星的改良EOF方案治疗晚期胃癌疗效较好,毒副作用可以很好耐受,值得临床进一步应用。     

奥沙利铂和5-氟尿嘧啶/醛氢叶酸双周疗法治疗晚期胃癌

目的评价奥沙利铂和5-氟尿嘧啶／醛氢叶酸双周疗法治疗晚期胃癌的疗效及安全性。方法26例晚期胃癌患者均有可评价的病灶，25例完成下例方案：奥沙利铂85mg／m^2及醛氢叶酸(LV)200mg／m^2(2小时静脉滴注)，随后5-氟尿嘧啶(5-Fu)400mg／m^2(10分钟静注)，5-Fu 600mg／m^2持续静脉输注22h，醛氢叶酸及5-Fu连用两天，每2周重复1次，每2次为1个疗程，所有患者至少接受2个疗程的治疗。结果完全缓解2例，部分缓解12例，总有效率56％(14／25)，中位缓解期3个月。无治疗相关死亡，主要不良反应为轻度的外周神经系统感觉障碍，恶心呕吐，白细胞及血红蛋白降低。结论奥沙利铂和5-氟尿嘧啶／醛氢叶酸双周疗法对晚期胃癌疗效确切，毒副反应轻，拓展了晚期胃癌患者化疗方案的选择。     

Oxaliplatin combined with 5-fluorouracil, leucovorin regimen for patients with advanced colorectal cancer

Objective： To observe the efficacy and tolerability of continuously infusing 5-fluorouracil （5-FU） / folic acid combined with oxaliplatin （L-OHP/5-FU/LV regimen） as first line treatment in advanced colorectal cancer. Methods： 23 patients of advanced colorectal cancer were treated with 5-FU 500 mg/d, civ, d 1-d5, d8-d12, leucovorin 100 mg/d, iv gtt, d1, d8, folic acid tablet 60 mg/d, po, d2-d5, d9-d12, and oxaliplatin 65 mg/（m^2·d）, iv gtt, dl, d8, repeated every 21 days （one cycle）. The effect was evaluated after two cycles. Results： Complete response in 2 cases and partial response in 10 cases were observed with an overall response rate of 47.18%. Adverse effects were mainly grade 1-2, including nausea, vomiting, diarrhea, dental ulcer, peripheral neuritis and myelosuppression. Conclusion： L-OHP/5-FU/LV regimen is an effective and better tolerated alternative treatment in advanced colorectal cancer and yields promising clinical application.     

草酸铂联合氟尿嘧啶、醛氢叶酸治疗晚期结直肠癌的临床观察

Objective:To observe the efficacy and tolerability of continuously infusing 5-fluorouracii(5-FU)/folic acid combined with oxaliplatin(L-OHP/5-FU/Lv regimen)as first line treatment in advanced colorectal cancer.Methods:23 patients of advanced colorectal cancer were treated with 5-Fu 500mg/d,civ,d1-d5,d8-d12,leucovorin 100mg/d,iv gtt,d1,d8,folic acid tablet 60 mg/d,po,d2-d5,d9-d12,and oxaliplatin 65mg/(m2-d),iv gtt,d1,d8,repeated every 21 days(one cycle).The effect was evaluated after two cycles.Results:Complete response in 2 cases and partial response in 10 cases were observed with an overall response rate of 47.18%.Adverse effects were mainly grade 1-2,including nausea,vomiting,diarrhea,dental ulcer,peripheral neuritis and myelosuppression.Conclusion:L-OHP/5-FU/LV regimen is an effective and better tolerated alterna tive treatment in advanced colorectal cancer and yields promising clinical application.     

Oxaliplatin, 5-fluorouracil/leucovorin and epirubicin as first-line treatment in advanced gastric carcinoma: a phase II study

The association between oxaliplatin and 5-fluorouracil (5-FU) has been extensively reported to improve prognosis of gastric cancer patients. The present study is aimed at evaluating response rate and the toxicity profile of the association with oxaliplatin, 5-FU/lecovorin and epirubicin in gastric cancer patients with locally advanced or metastatic disease. Thirty-six patients have been enrolled and 35 evaluated. The treatment schedule was oxaliplatin (100 mg m(-2)), 5-FU (400 mg m(-2)), leucovorin (40 mg m(-2)) and epirubicin (60 mg m(-2)) intravenously. administered every 3 weeks for 6 months, for a total of 185 therapy cycles . Response rate and toxicity were assessed according to the international WHO criteria. Every patient received a mean of 5.3 therapy cycles in a day-hospital setting. Sixteen of 35 patients (46%) showed an objective response, two complete response and 14 partial response. Median time to progression was 33 weeks with an overall median survival of 49 weeks. During the study, anaemia grade 3 and neutropenia grade 3 were observed in 9 and 11% of patients respectively. A grade 3 periferic sensorial neuropathy was observed in 6% of patients. No life threatening or cardiac toxicity was recorded. The regimen used showed anticancer activity against gastric carcinoma, a tolerable toxicity profile and excellent patient compliance.     

Phase II study of weekly oxaliplatin and 24-h infusion of high-dose 5-fluorouracil and folinic acid in the treatment of advanced gastric cancer

To investigate the efficacy and safety of combining weekly oxaliplatin with weekly 24-h infusion of high-dose 5-fluorouracil (5-FU) and folinic acid (FA) in treatment of patients with advanced gastric cancer. Patients with histologically confirmed, locally advanced or recurrent/metastatic gastric cancer were studied. Oxaliplatin 65 mg m(-2) 2-h intravenous infusion, and 5-FU 2600 mg m(-2) plus FA 300 mg m(-2) 24-h intravenous infusion, were given on days 1 and 8, repeated every 3 weeks. Between January 2001 through January 2002, 55 patients were enrolled. The median age was 64 years (range: 22-75). In all, 52 patients (94.5%) had recurrent or metastatic disease and three patients had locally advanced disease. Among 50 patients evaluable for tumour response, 28 patients achieved partial response, with an overall response rate of 56% (95% confidence interval (CI): 41.8-70.3%). All 55 patients were evaluated for survival and toxicities. Median time to progression and overall survival were 5.2 and 10.0 months, respectively, during median follow-up time of 24.0 months. Major grades 3-4 toxicities were neutropenia in 23 cycles (7.1%) and thrombocytopenia in 16 cycles (5.0%). Treatment was discontinued for treatment-related toxicities in nine patients (16.4%), of whom eight were due to oxaliplatin-related neurotoxicity. One patient (1.8%) died of neutropenic sepsis. This oxaliplatin-containing regimen is effective in the treatment of advanced gastric cancer. Except for neurotoxicity that often develops after prolonged use of oxaliplatin, the regimen is well tolerated.     

奥沙利铂联合5-FU和吡柔比星治疗晚期胃癌临床疗效分析

目的:观察奥沙利铂联合5-FU和吡柔比星治疗晚期胃癌的疗效及不良反应.方法:36例晚期胃癌患者,初治20例,复治16例.吡柔比星40mg/m2静脉注射d1,奥沙利铂130mg/m2静脉滴注2小时d1,5-FU 375mg/m2·d1-5静脉滴注,每3周重复,每化疗2个周期评价1次疗效. 结果: 36例患者中,总缓解率 44.37%,完全缓解1例,部分缓解41.6%(15例).初治病例缓解率45%(9/20),复治病例缓解率31.25%(5/16).KPS评分提高10分以上者15例(15/36).主要的Ⅲ-Ⅳ度不良反应为:中性粒细胞减少27.7%(10/36),血小板减少13.8%(5/36),贫血16.6%(6/36),恶心呕吐22.2%(8/36).结论:奥沙利铂联合5-FU及吡柔比星治疗晚期胃癌疗效较好,不良反应可以耐受,值得临床进一步应用.     

Phase I study of a weekly schedule of oxaliplatin, high-dose leucovorin, and infusional fluorouracil in pretreated patients with advanced colorectal cancer

Purpose:To identify the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) of oxaliplatin (L-OHP) given on a weekly schedule including fixed doses of leucovorin (LV) and infusional 5-fluorouracil (5-FU), to define the toxicity profile of this regimen and to find preliminary evidence of its activity in pretreated patients with metastatic colorectal cancer (MCRC). Patients and methods: Twenty-one patients with progressive disease, treated with fluoropyrimidines and with histologically measurable MCRC entered into this phase I study. Fixed doses of LV (500 mg/m²) followed by a 48-hour 5-FU 2600 mg/m² infusion (5-FU_48h) were administered with escalating doses of L-OHP, starting from 60 mg/m² and with stepwise increments of 5 mg/m². No intra-patient dose escalation was allowed. Treatment was given once a week for four consecutive weeks, followed by a one-week rest period. Results:Three dose levels were tested. The MTD was L-OHP 70 mg/m² since two of the three patients showed dose-limiting diarrhea and the third developed neutropenia during the first cycle of chemotherapy. Most patients complained of mild peripheral sensitive neurotoxicity, which was related to the cumulative dose of L-OHP. Treatment delays were necessary for a total of 42 cases, but only in 11 of 42 after the pre-arranged 10% dose reduction of 5-FU (2300 mg/m²). Sixteen patients were evaluable for response: seven (33%; 95% confidence interval (CI): 14.6%–57.0%) were considered to show a major response (one complete), six showed a stable disease, and in addition progressive disease was observed in three patients. Conclusions:Our results show that L-OHP, LV and 5-FU can be administered safely and repetitively using a weekly schedule. Diarrhea and neutropenia are the DLT of this regimen. Its activity and its manageable toxicity profile deserve further evaluation in chemotherapy-naïve MCRC patients. The doses recommended for phase II trials are: L-OHP 65 mg/m², LV 500 mg/m² and 5-FU_48h 2300 mg/m² infusion given on a weekly-times-four schedule followed by a one-week rest period.     

A phase II study of biweekly oxaliplatin plus infusional 5-fluorouracil and folinic acid (FOLFOX-4) as first-line treatment of advanced gastric cancer patients

The aim of the study was to assess the toxicity and the clinical activity of biweekly oxaliplatin in combination with infusional 5-fluorouracil (5-FU) and folinic acid (FA) administered every 2 weeks (FOLFOX-4 regimen) in patients with advanced gastric cancer (AGC). A total of 61 previously untreated AGC patients were treated with oxaliplatin 85 mg m(-2) on day 1, FA 200 mg m(-2) as a 2 h infusion followed by bolus 5-FU 400 mg m(-2) and a 22 h infusion of 5-FU 600 mg m(-2), repeated for 2 consecutive days every 2 weeks. All patients were assessable for toxicity and response to treatment. Four (7%) complete responses and 19 partial responses were observed (overall response rate, 38%). Stable disease was observed in 22 (36%) patients, with progressive disease in the other six (10%) patients. Median time to progression (TTP) and median overall survival (OS) were 7.1 and 11.2 months, respectively. National Cancer Institute Common Toxicity Criteria grade 3 and 4 haematologic toxicities were neutropenia, anaemia and thrombocytopenia in 36, 10 and 5% of the patients, respectively. Grade 3 peripheral neuropathy was recorded in three (5%) patients. FOLFOX-4 is an active and well-tolerated chemotherapy. Response rate (RR), TTP and OS were comparable with those of other oxaliplatin-based regimens, suggesting a role for this combination in gastric cancer.     

A phase II study of irinotecan with bi-weekly, low-dose leucovorin and bolus and continuous infusion 5-fluorouracil (modified FOLFIRI) as salvage therapy for patients with advanced or metastatic gastric cancer

OBJECTIVE: This phase II study was designed to assess the safety and efficacy of a modified FOLFIRI regimen (irinotecan with bi-weekly, low dose leucovorin (ldLV) and bolus and continuous infusion with 5-fluorouracil (5-FU)) as a salvage therapy for patients with advanced or metastatic gastric cancer. METHODS: Patients were treated with irinotecan 150 mg/m(2) on day 1 and received ldLV 20 mg/m(2) followed by 5-FU 400 mg/m(2) (bolus) and 5-FU 600 mg/m(2) (22 h continuous infusion) on days 1 and 2 every 14 days. RESULTS: A total of 36 patients were assigned to treatment. The median patient age was 55 years (range 31-70), and 55.6% (20/36) of the patients had performance status (ECOG) of 0 or 1.The median follow-up duration was 15.5 (range 2.6-36.4) months. Of the 30 patients evaluated for their tumor response, three achieved a partial response, with an overall response rate of 10.0% (95% CI 0.0-21.0%). Eleven patients (36.7%) showed stable disease. The median time to progression was 3.3 (95% CI 2.0-4.6) months, and the median overall survival time was 10.9 (95% CI 6.1-15.7) months. The median number of cycles of modified FOLFIRI treatment was 3 (range 1-9 cycles). Grade III or IV neutropenia was observed in 23 cycles (17.6%), and febrile neutropenia occurred in three cycles (2.3%). Grade III nausea/vomiting was found in one patient (2.8%). There was one episode of UGI bleeding, but there were no treatment-related deaths. CONCLUSION: The modified FOLFIRI regimen described here appears a safe and feasible salvage therapy in advanced gastric cancer patients.     

Whole-body hyperthermia (41.8 degrees C) combined with bimonthly oxaliplatin, high-dose leucovorin and 5-fluorouracil 48-hour continuous infusion in pretreated metastatic colorectal cancer: a phase II study.

BACKGROUND: Second- and third-line treatments remain a challenge in advanced colorectal cancer. Studies of bimonthly regimens of high-dose leucovorin (LV) and 5-fluorouracil (5-FU) by continuous infusion combined with oxaliplatin (L-OHP) have shown encouraging response rates in patients not responding to a bimonthly LV/5-FU regimen. Hyperthermic enhancement of L-OHP efficiency by increased DNA adduct formation has been demonstrated in vitro. This study was designed to address feasibility, toxicity and efficacy issues of whole-body hyperthermia (WBH) as an adjunct to L-OHP/LV/5-FU in pretreated patients after progression to first- and second-line treatments with LV/5-FU by continuous infusion and irinotecan. PATIENTS AND METHODS: Forty-four patients with advanced colorectal cancer, who had progressed during or within 3 months after completion of chemotherapy with LV/5-FU 24-h infusion (LV/5-FU(24h)) (eight patients) or irinotecan combined with or after LV/5-FU(24h )(36 patients), were treated with L-OHP 85 mg/m(2), 2-h intravenous (i.v.) infusion, followed by LV 200 mg/m(2), 1-h i.v. infusion, and 5-FU 3 g/m(2), 48-h continuous infusion. Every second cycle of the biweekly regimen was combined with WBH, thus allowing a comparison of toxicity with and without WBH in the same patient. Whole-body hyperthermia was administered by a humidified radiant heat device. The target temperature of 41.8 degrees C was maintained for 60 min. L-OHP (2-h infusion) was started at a core body temperature of 39 degrees C. RESULTS: All patients could be evaluated for toxicity, and 41 patients were evaluable for response. A total of 273 L-OHP-containing regimens were administered, 130 with and 143 without WBH. Hyperthermic treatment combined with L-OHP/LV/5-FU showed no unexpected toxicities. WHO grade 3 toxicities were rare and evenly balanced between cycles given with or without WBH. One early death occurred due to sepsis and tumor lysis. The overall response rate was 20%, with two complete and six partial responses. Twenty-three patients (56%) had stable disease and nine patients (22%) progressive disease. With a median observation time of 70 weeks, the median time to progression was 21 weeks [95% confidence interval (CI) 17-25 weeks] and the median survival was 50 weeks (95% CI 39-61 weeks) from the start of therapy. CONCLUSIONS: This trial suggests some advantage of combining L-OHP/LV/5-FU with WBH. Results compare favorably with the activity of similar regimens without WBH in less extensively pretreated patients. These data support further evaluation and warrant phase III studies.     

Oxaliplatin plus high-dose leucovorin and 5-fluorouracil in pretreated advanced breast cancer: a phase II study.

BACKGROUND: The purpose of this study was to evaluate the efficacy and toxicity of oxaliplatin plus 5-fluorouracil (5-FU) and leucovorin (LV) in patients with metastatic breast cancer (MBC) previously treated with anthracyclines and taxanes. PATIENTS AND METHODS: Fifty anthracycline- and taxane-pretreated MBC patients were treated with oxaliplatin 85 mg/m(2) as a 2-h infusion on day 1, LV 200 mg/m(2)/day as a 2-h infusion followed by bolus 5-FU 400 mg/m(2)/day and a 22-h infusion of 5-FU 600 mg/m(2)/day for 2 consecutive days. Treatment was repeated every 3 weeks. Patients were evaluated for response every two cycles. RESULTS: The median age was 51 years (range 34-75). Twenty patients (40%) had received three or more chemotherapeutic regimens, 64% had three or four metastatic sites and 78% had visceral metastases. All patients had prior exposure to anthracyclines and taxanes. Based on an intention-to-treat analysis, one patient (2%) achieved a complete response and 16 (32%) a partial response, for a 34% overall response rate. Twenty-one patients (42%) had stable disease and 12 (24%) progressive disease. The median time to tumor progression was 5.3 months (range 0.5-12.8) and the median overall survival was 12.3 months (range 0.5-19.2). Toxicity was mild to moderate. Grade 3/4 neutropenia and thrombocytopenia occurred in 32% and 18%, respectively. Febrile neutropenia was experienced by three patients (6%), who were successfully treated. Grade 3/4 neurotoxicity was reported in 14% of the patients and gradually declined after treatment discontinuation. Cycle delays were reported in 28% of patients and dose reductions in 26%. Alopecia, nausea-vomiting, diarrhea and mucositis were not significant. There were no treatment-related deaths. CONCLUSION: The combination of oxaliplatin plus 5-FU/LV seems to be an active regimen in patients with MBC and prior exposure to anthracyclines and taxanes with a good safety profile. The incidence of severe toxicity was quite low and the compliance of patients to the treatment was satisfactory. The results obtained with this regimen could be considered encouraging in this heavily pretreated group of breast cancer patients with a high incidence of visceral metastases.     

A phase II study of irinotecan with 5-fluorouracil and leucovorin in patients with previously untreated gastric adenocarcinoma

Background:A phase II study testing the safety and efficacyof irinotecan (CPT-11), 5-fluorouracil (5-FU), and leucovorin (LCV)was conducted in patients with advanced gastric adenocarcinomas. Patients and methods:Patients with metastatic or recurrentadenocarcinoma of the gastroesophageal junction (GEJ) or stomach wereentered onto this study. Previous chemotherapy for metastatic diseasewas not allowed. Treatment consisted of repeated 6-week cyclescomprising CPT-11 125 mg/m² intravenously (i.v.) followedimmediately by LCV 20 mg/m² i.v. and 5-FU 500mg/m² i.v., all given weekly for four weeks followed by atwo-week rest. Results:Thirty-eight patients wereenrolled and 36 eligible patients received protocol therapy. Grade3–5 toxicities consisted primarily of neutropenia (36%) anddiarrhea (28%). Neutropenic infection was observed in 14%of patients, with 3 (8%) dying of neutropenic sepsis. The overallresponse rate was 22% (95% confidence interval [CI]8.5% to 35.5%). Median survival was 7.6 months, and mediantime to progression was 4.4 months. Conclusion:Thisweekly regimen of CPT-11 with bolus 5-FU/LCV is active in patients withadvanced adenocarcinomas of the stomach or gastroesophageal junction.While rates of grade 3–4 neutropenia and diarrhea were similar tothose observed historically in patients receiving this regimen forcolorectal cancer, neutropenic fever/sepsis appeared to be morefrequent, and dose modifications were substantial. Future trials of thiscombination in patients with gastric cancer should decrease the absolutestarting drug doses and/or employ altered scheduling that betteraccommodates the pattern of toxicity.     

Clinical pharmacokinetics of oxaliplatin in a hemodialysis patient with advanced gastric cancer

We administered FOLFOX (oxaliplatin (L-OHP) plus infusional 5-fluorouracil (5-FU) and leucovorin) to an hemodialysis (HD) patient with advanced gastric cancer (AGC), and investigated pharmacokinetics (PKs) and dialyzability of L-OHP. The patient was a 54-year-old Japanese man with a diagnosis of inoperable AGC. FOLFOX was instituted 3?h prior to the start of a 4?h HD period with the L-OHP and 5-FU doses reduced by 50% for the first cycle, and 30% reduced dose was administered for the second cycle. We performed an analysis of the PKs of L-OHP during these two cycles. Volume of distribution and area under the curve of the 30% reduced L-OHP dose were 56.7?L and 30.0?μg·h/mL, respectively. A dose reduction of L-OHP by 30%?50% may be advisable for the initial administration, given the need for careful administration of chemotherapy in HD patients, with particular attention to the development of hematological toxicities and neuropathy.     

卡培他滨与氟尿嘧啶/亚叶酸钙联合奥沙利铂治疗晚期胃癌的随机对照临床研究

背景与目的：目前对进展期及转移性胃癌还没有标准的化疗方案,而且缺乏有效率高、毒副反应小、安全的化疗方案.毒副反应是晚期胃癌化疗的限制性因素,影响患者的生活质量.本研究观察及比较两种常用化疗方案卡培他滨联合奥沙利铂方案（XELOX）与氟尿嘧啶/亚叶酸钙联合奥沙利铂方案（FOLFOX4）治疗晚期胃癌的临床疗效及毒副反应,以期取得在较佳疗效保证的同时,毒副反应小,耐受性更好的效果.方法：48例晚期胃癌患者随机分成两组,XELOX组与FOLFOX4组.XELOX组25例,用卡培他滨联合奥沙利铂方案化疗,卡培他滨1000 mg/m^2,口服,2次/日,第1～14天;奥沙利铂130 mg/m^2,静脉点滴,第l天;2l d为1个周期.FOLFOX4组23例,用氟尿嘧啶/亚叶酸钙联合奥沙利铂方案化疗,奥沙利铂85 mg/m^2,静脉点滴,第1天;亚叶酸钙200 mg/m^2,静滴2 h后予氟尿嘧啶400 mg/m^2,推注,后续600 mg/m^2持续静滴22 h,第1、2天;每2周重复,4周为1周期.两组均治疗2周期以上.按wH0标准评价客观疗效和毒副反应.结果：入组48例均可评价疗效,XELOX组有效率56.0%,中位TTP 5.8个月,MST 10个月,FOLFOX4组有效率47.8%,中位TTP 5.7个月,MST 9.8个月.两组近期有效率差异无显著性.毒副反应比较,手足综合征以：XELOX组显著（P＜0.05）,Ⅲ/Ⅳ级恶心呕吐发生率以FOLFOX4.组显著（P＜0.05）,其余毒副反应除腹泻外发生率以FOIFOX4组稍高,但差异无显著性.结论：XELOX方案与FOLFOX4方案治疗晚期胃癌疗效确切,毒副反应能耐受.两组近期疗效相似,毒副反应以XELOX组更易耐受,尤其对一般情况欠佳及老年的患者耐受性好.     

Phase II study of irinotecan, 5-fluorouracil and leucovorin as first-line therapy for advanced colorectal cancer

BACKGROUND: We evaluated the efficacy and tolerability of a modified biweekly irinotecan, 5-fluorouracil and leucovorin regimen (modified Douillard regimen) as the first-line therapy in patients with advanced colorectal cancer. METHODS: A total of 80 patients (41 male, 39 female) with recurrent or metastatic colorectal cancer were enrolled between April 2001 and December 2003. The treatment cycle consisted of irinotecan 150 mg/m(2) as a 90 min infusion on day 1, leucovorin 20 mg/m(2) intravenous bolus, immediately followed by a 48 h continuous infusion of 5-fluorouracil 3000 mg/m(2) on day 1. The primary end-point was response rate, and the secondary end-points were time to progression and toxicity profile. RESULTS: An overall objective response rate of 38.7% [95% confidence interval (CI) 27.84-49.66%] was achieved. The median time to progression was 6.1 months (95% CI 4.63-7.57 months) and the median overall survival time was 20.2 months (95% CI 15.50-24.90 months). The median duration of follow-up for patients was 16.9 months. The toxicity profile was more favorable than for the conventional Douillard regimen. CONCLUSION: We conclude that the modified Douillard regimen may be a practical and more tolerable treatment option in patients with advanced colorectal cancer.     

Treatment of advanced gastric carcinoma patients with calcium folinate, a 5-fluorouracil bolus and continous infusion with 5-fluorouracil combined with oxaliplatin

Objective  To examine the therapeutic effects and toxicity of high-dose-folinic acid plus a 5-fluorouracil (5-FU) bolus and continuous infusion with 5-FU combined with locally produced oxaliplatin (L-HOP)in treating advanced gastric carcinoma patients. Methods  Sixty-five patients with advanced gastric carcinoma were treated with high-dose-folinic acid plus a 5-FU bolus and a 48-h continuous infusion of 5-FU combined with oxaliplatin. The effects of treatment and toxicity were observed. Results  There were 4 complete responses, 26 partial responses, 30 with no change and 5 with progressive disease. The overall effective response rate was 46.2% (30/65). The median duration was 7 months, with the main side effects including nausea and vomiting, peripheral phlebitis, alopecia, leukopenia, dental ulcers, peripheral neuritis and diarrhea. All the side effects were tolerated and minimal. Conclusion  The results showed that high-dose folinic acid plus a 5-FU bolus and continuous infusion of 5-FU combined with oxaliplatin appears to be a safe and effective therapy for patients with advanced gastric carcinoma. This therapeutic regimen is of value for these patients.     

Phase II study of cisplatin, gemcitabine and 5-fluorouracil in advanced pancreatic cancer.

BACKGROUND: The aim of this study was to determine the activity of the combination of cisplatin, gemcitabine and 5-fluorouracil (5-FU) as therapy for metastatic or locally advanced inoperable pancreatic adenocarcinoma. PATIENTS AND METHODS: Patients with histologically proven advanced or metastatic pancreatic adenocarcinoma received first-line chemotherapy comprising cisplatin (20 mg/m2 on days 1, 8, 15, 22, 29 and 36), gemcitabine (1000 mg/m2 on days 1, 8, 29 and 36) and 5-FU (200 mg/m2 as continuous infusion on days 1-42) every 56 days. RESULTS: A total of 34 patients were studied. Eighty courses were administered (median two courses per patient). Among 32 patients evaluable for response, two patients had a complete response and four a partial response for an overall response rate of 19% (95% confidence interval 7% to 36%). Thirteen patients had stable disease (40%) and 13 progressed. Median progression-free survival was 4.7 months, median survival 9.0 months and 26% of patients achieved 1-year survival. Ten of 25 patients (40%) with pain at presentation had a sustained reduction of analgesic consumption. The principal grade 3/4 toxicities were neutropenia, thrombocytopenia, anaemia and mucositis, occurring in 24%, 21%, 9% and 3% of patients. CONCLUSION: This schedule seems well tolerated and active in pancreatic cancer and worthwhile of further evaluation.     

草酸铂联合氟尿嘧啶、甲酰四氢叶酸治疗晚期大肠癌临床疗效观察

目的观察应用草酸铂联合氟尿嘧啶、甲酰四氢叶酸治疗晚期大肠癌的客观疗效及不良反应。方法草酸铂联合甲酰四氢叶酸和氟尿嘧啶持续静脉滴注46小时治疗晚期大肠癌48例(L-OHP130mg/m2静注2小时,d1,CF400mg/m2静脉输注2小时,d2,再接5-FU3.0g/m2用输液泵连续静注46小时,以上治疗方案每2周重复一次,化疗第5~11天均给予升白支持),所有病人均接受3个周期以上化疗。结果PR 23例,SD 18例,PD 7例,总有效率47.9%,中位疾病无进展期6.6个月,中位生存期10.5个月,1年生存率36.8%。主要不良反应有恶心、呕吐、黏膜炎、外周神经炎等。毒性反应多为Ⅰ~Ⅱ度,病人耐受良好。结论应用草酸铂联合氟尿嘧啶、甲酰四氢叶酸治疗晚期大肠癌疗效确切,不良反应轻微,值得临床推广使用。