Treatment of Advanced Gastric Cancer with a Modified Regimen of Etoposide/Leucovorin/5-Fluorouracil

The efficacy and toxicity of a combination of etoposide 100 mg/m²/day iv on day 2-4, leucovorin 300 mg/m²/day iv, and 5-FU 500 mg/m² day iv on day 1-5 every 4 weeks were assessed in 21 patients with advanced gastric cancer with measurable or evaluable diseases. Eight patients had an objective response, including 3 in CR. The overall response rate was 38.1% (95% CI 33.4-42.8%). Five of 8 patients who exhibited locally advanced and unresectable diseases had an objective response (2 CR, 3 PR). The response rate in patients with metastatic disease was 23.0% (95% CI 14.4-31.6%). The median progression-free interval and overall survival time were 7 and 10 months, respectively. The most frequent side effect was alopecia (Gr I/II 71.4%). No treatment-related death occurred. Modified ELF is a relatively effective and tolerable combination regimen for advanced gastric cancer and can be safely administered to elderly patients and patients with systemic diseases.     

Randomised phase II evaluation of irinotecan plus high-dose 5-fluorouracil and leucovorin (ILF) vs 5-fluorouracil, leucovorin, and etoposide (ELF) in untreated metastatic gastric cancer

An open-label randomised comparison of efficacy and tolerability of irinotecan plus high-dose 5-fluorouracil (5-FU) and leucovorin (LV) (ILF) with etoposide plus 5-FU/LV (ELF) in patients with untreated metastatic or locally advanced gastric cancer. One cycle of ILF comprised six once-weekly infusions of irinotecan 80 mg m(-2), LV 500 mg m(-2), 24-h 5-FU 2000 mg m(-2), and ELF comprised three once-daily doses of etoposide 120 mg m(-2), LV 300 mg m(-2), 5-FU 500 mg m(-2). In all, 56 patients received ILF and 58 ELF. Median age was 62 years, Karnofsky performance 90%, and disease status was comparable for both arms. The objective clinical response rates after 14 weeks treatment (primary end point) were 30% for ILF and 17% for ELF (risk ratio (RR) 0.57, 95% confidence interval (CI) 0.29-1.13, P = 0.0766). Overall response rates over the entire treatment period for ILF and ELF were 43 and 24%, respectively (RR 0.56, 95% CI 0.33-0.97; P = 0.0467). For ILF and ELF, respectively, median progression-free survival was 4.5 vs 2.3 months, time to treatment failure was 3.6 vs 2.2 months (P = 0.4542), and overall survival was 10.8 vs 8.3 months (P = 0.2818). Both regimens were well tolerated, the main grade 3/4 toxicities being diarrhoea (18%, ILF) and neutropenia (57%, ELF). The data from this randomised phase II study indicate that ILF provides a better response rate than ELF, and that ILF should be investigated further for the treatment of metastatic gastric cancer.     

Phase II study of oxaliplatin, 5-fluorouracil and leucovorin in previously platinum-treated patients with advanced gastric cancer.

BACKGROUND: Oxaliplatin shows preclinical activity in many cancer cell lines that are resistant to cisplatin, and also has synergism with 5-fluorouracil (5-FU). We undertook this study to evaluate the efficacy and toxicities of a combined oxaliplatin, 5-FU and leucovorin (LV) continuous infusion regimen in patients with advanced gastric cancer who progressed during or after treatment with 5-FU and platinum compounds. PATIENTS AND METHODS: Twenty-six patients with advanced gastric cancer, whose disease progressed while receiving, or after discontinuing, chemotherapy with a 5-FU and platinum regimen, were enrolled in this study. Treatment comprised oxaliplatin (85 mg/m2 on day 1) as a 2-h infusion followed by bolus 5-FU (400 mg/m2 on day 1), and 48-h infusion of 5-FU 2.4-3.0 g/m2 concurrently with LV 150 mg/m2. Cycles were repeated at 2-week intervals. RESULTS: Of the 23 evaluable patients, there were six partial responses (response rate 26%). All responding patients were among those who entered into this trial immediately after failure of previous chemotherapy with 5-FU and cisplatin. The median time to progression was 4.3 months and the median overall survival was 7.3 months. The most common hematologic toxicity was grade 1-2 anemia in 39 cycles (39%). No grade 4 leukopenia or thrombocytopenia were observed. The most common non-hematologic toxicity was nausea/vomiting (33%). Peripheral neuropathy of grade 1 or 2 was noted (27%), but there was no grade 3 or 4 neurotoxicity. CONCLUSIONS: This phase II study of oxaliplatin, 5-FU and LV continuous infusion showed activity in previously platinum-treated patients with advanced gastric cancer, with acceptable toxicities.     

Combination of folinic acid, 5-fluorouracil bolus and infusion, and cisplatin (LV5FU2-P regimen) in patients with advanced gastric or gastroesophageal junction carcinoma.

BACKGROUND: Combination chemotherapy with continuous 5-fluorouracil (5-FU) and cisplatin in a monthly regimen is one of the standard treatments for advanced gastric carcinoma. This study evaluated the new LV5FU2-P regimen, designed to improve efficacy and tolerance of the 5-FU plus cisplatin combination. PATIENTS AND METHODS: Forty-three patients with advanced or metastatic gastroesophageal junction or gastric carcinoma were prospectively included in the study. They were treated every 14 days with cisplatin 50 mg/m(2) on day 2 plus folinic acid 200 mg/m(2)/day as a 2-h intravenous (i.v.) infusion on days 1 and 2, plus bolus 5-FU 400 mg/m(2)/day on days 1 and 2, plus continuous 5-FU 600 mg/m(2)/day as a 22-h i.v. infusion on days 1 and 2. Ten patients received a simplified regimen (folinic acid 40 mg/m(2) day 1 + bolus 5-FU 400 mg/m(2) day 1 + continuous 5-FU 2400 mg/m(2) on days 1 and 2 with cisplatin 50 mg/m(2) on day 2). RESULTS: All the patients were assessable for response and 42 for toxicity. One patient achieved a complete response and 15 a partial response, for an overall response rate of 37.2% [95% confidence interval (CI) 22.1% to 52.3%]. The median progression-free survival was 7.2 months (95% CI 5.4-10.9) and the overall survival was 13.3 months (95% CI 10.1-16.4). There were no treatment-related deaths. Hematological and gastrointestinal toxicities were the most common severe toxicities. CONCLUSIONS: LV5FU2-P is an active and well tolerated regimen in the treatment of advanced gastroesophageal junction or gastric carcinomas. It warrants evaluation comparatively with other active regimens.     

Cyclophosphamide plus 5-FU versus 5-FU alone in advanced gastric carcinoma

30 patients with advanced metastatic gastric adenocarcinoma, having a measurable indicator lesion, were randomized (1:2) to receive (intravenously) either weekly 5-fluorouracil alone (15 mg/kg) or combination treatment with cyclophosphamide (20 mg/kg) given on day 1 and 5-FU (15 mg/kg) given weekly on weeks 2-5, beginning on day 8. The combination cycle was repeated at 6-week intervals. Although the toxic effects of therapy were similar in both arms, the addition of cyclophosphamide to the single-agent 5-FU regimen did not increase either the frequency of objective response (5-FU 18%, combination 16%) or improve the median survival of patients with advanced measurable gastric carcinoma (5-FU 4.4 months, combination 5.2 months). Patients with pretreatment weight loss greater than 10% had significantly (p less than 0.05) shorter median survival (2.8 versus 5.6 months) compared to patients without weight loss.     

以草酸铂为主的联合化疗方案治疗晚期胃癌

目的 :目的 :观察草酸铂 (L OHP)联合氟尿嘧啶 (5 FU)、甲酰四氢叶酸钙 (CF)和足叶乙甙 (VP 16 )治疗晚期胃癌的疗效。方法 :采用随机分组方法将 5 3例晚期胃癌患者分为两组 ,治疗组 2 7例 ,用L OHP 130mg/m2 ,加于葡萄糖注射液中静滴 3小时 ,第 1天 ;CF 10 0mg/m2 ,静滴第 1～ 5天 ;5 FU 30 0mg/m2 ,于CF后静滴 ,维持 6小时 ,第 1～ 5天 ;VP 1610 0mg ,静滴 ,第 1～ 3天 ;对照组 2 6例用DDP 80mg/m2 ,静滴第 1天 ,CF、5 FU和VP 16用法同治疗组。每 3～ 4周为一个周期。二个周期评价疗效。结果 :治疗组CR 3例 ,PR 15例 ,总有效率 6 6 7% ;对照组CR 1例 ,PR 9例 ,总有效率为 38 5 %。两组总有效率间差异有显著性 (P <0 0 5 )。治疗组周围感觉神经毒性发生率较对照组高 ,恶心、呕吐的发生率较对照组低 ,两组间差异均有显著性 (P <0 0 5 )。结论 :L OHP联合CF、5 Fu和VP 16方案治疗晚期胃癌疗效较好 ,不良反应轻 ,能耐受 ,值得进一步在临床推广使用     

Combination chemotherapy with granulocyte-macrophage-colony stimulating factor in patients with locoregional and metastatic gastric adenocarcinoma.

BACKGROUND: A combination of etoposide, 5-fluorouracil, and folinic acid (ELF) remains popular for the treatment of patients with gastric carcinoma and has been reported to result in a response rate of up to 40% with good patient tolerance. The authors elected to add granulocyte-macrophage-colony stimulating factor (GM-CSF) to ELF to determine whether the response rate could be increased in patients with untreated advanced gastric carcinoma. METHODS: Previously untreated patients with measurable metastatic tumor were studied. Outpatient therapy was comprised of etoposide, 120 mg/m2 intravenously (i.v.), on Days 1-3; 5-fluorouracil, 500 mg/m2 i.v., on Days 1-3; and folinic acid, 300 mg/m2 i.v., on Days 1-3. Courses were repeated every 21 days. GM-CSF (at a dose of 250 microg/m2/day for 14 days from Day 4) was added after the first course of ELF if patients developed Grade 4 neutropenia in a previous course. RESULTS: Thirty patients were enrolled and 29 were evaluable for response. Four patients (14%) achieved a partial response (median duration of response, 6.5 months). The median duration of survival was 7.8 months. Grade 4 neutropenia occurred in 16 patients who then received GM-CSF. A similar rate of neutropenic fever was observed in courses both with or without GM-CSF (15% in courses without GM-CSF and 16% in courses with GM-CSF); however, a higher nadir absolute granulocyte count (1300 cells/microL) occurred in courses with GM-CSF compared with courses without GM-CSF (300 cells/microL). CONCLUSIONS: The ELF regimen resulted in a much lower response rate than reported in the literature. The attempt to improve the efficacy of this regimen by the addition of GM-CSF did not prove successful. The authors believe this regimen cannot be recommended for the treatment of patients with advanced gastric carcinoma outside of a protocol setting.     

Chemotherapy with low-dose CDDP and continuous 5-FU for the treatment of advanced gastric cancers]

INTRODUCTION: 5-fluorouracil (5-FU) has been widely used for the treatment of gastrointestinal cancers. On the basis of recent findings, low-dose Cisplatin (CDDP) and continuous venous infusion of 5-FU have shown additive or synergistic antitumor effects in experimental models. We evaluated clinical effects of low-dose CDDP and 5-FU (low-dose FP therapy) in patients with advanced gastric cancers. PATIENTS AND METHODS: In December 1993 and June 1998, 52 patients with advanced gastric cancer were entered in this study. Patients were considered eligible if they had a bidimensionally measurable tumor. 5-FU (160 mg/m2/day) was continuously infused over 24 hours using an implantable port, and CDDP (3 mg/m2/day) was infused for half an hour. The administration schedule consisted of 5-FU for 7 consecutive days and CDDP for 5 days followed by a 2-day rest every four weeks according to response and tolerance. RESULTS: Low-dose FP therapy was given 44 patients (85%). The response rate was 65.9% and median survival time was 249 days. The responder group showed good survival compared with the non-responder group. The regimen was tolerable, and the most common toxicity was anorexia (40.3%). Three patients suffered from grade 3 anorexia, leukopenia and mucositis. On the other hand, renal dysfunction occurred in 50% (two of four patients administered over 1,000 mg CDDP). These results raise the possibility that the dose-limiting factor of low-dose FP therapy may account for the total dosage of CDDP. CONCLUSION: Low-dose FP therapy promises to be effective in the clinical management of advanced gastric cancer.     

Fluorouracil modulation in colorectal cancer: lack of improvement with N -phosphonoacetyl- l -aspartic acid or oral leucovorin or interferon, but enhanced therapeutic index with weekly 24-hour infusion schedule--an Eastern Cooperative Oncology Group/Cancer and Leukemia Group B Study.

PURPOSE: To investigate mechanism-directed regimens in maximizing the efficacy of fluorouracil (5-FU) in advanced colorected cancer. PATIENTS AND METHODS: Based on promising phase II data, a randomized comparison of various methods for the biochemical modulation of 5-FU was undertaken in patients with advanced colorectal cancer. The control group received single-agent 5-FU as a 24-hour infusion weekly. Patients (N = 1,120) with no prior chemotherapy for metastatic disease were randomized to one of the following arms: arm A, 5-FU 2,600 mg/m2 by 24-hour infusion, weekly; arm B, N-phosphonoacetyl-l-aspartic acid 250 mg/m2 day l, 5-FU 2,600 mg/m2 by 24-hour infusion day 2, weekly; arm C, 5-FU 600 mg/m2 with oral leucovorin (LV) 125 mg/m2 hourly for the preceding 4 hours, weekly; arm D, 5-FU 600 mg/m2 with intravenous (IV) LV 600 mg/m2, weekly; arm E, 5-FU 750 mg/m2/d IV by continuous infusion for 5 days, then 750 mg/m2 weekly, and recombinant interferon alfa-2a 9 million units subcutaneously three times weekly. Median follow-up was 4.8 years. RESULTS: Of the 1,098 assessable patients, 57% had measurable disease. The toxicity of all the regimens was tolerable. Grade 4 or worse toxicity occurred in 11%, 11%, 30%, 24%, and 22% on each arm, respectively; diarrhea was the most common adverse effect. These toxicity patterns favored significantly (P <.001) the 24-hour infusion arms. Median survival (months) by arm was A, 14.8; B, 11.9; C, 13.5; D, 13.6; and E, 15.2. These survival durations did not differ significantly. CONCLUSION: We conclude that a weekly infusion regimen of 5-FU is significantly less toxic than and as effective as 5-FU bolus regimens modulated by either LV or interferon in patients with metastatic colorectal cancer.     

Preliminary clinical evaluation of low-dose CDDP and continuous 5-FU therapy for advanced gallbladder cancer

5-fluorouracil (5-FU) has been widely used for the treatment of gastrointestinal cancers. Low-dose cisplatin (CDDP) and continuous venous infusion of 5-FU have recently shown additive or synergistic antitumor effects in experimental models. In this study, we evaluated the clinical effects of low-dose CDDP and 5-FU (low-dose FP therapy) in patients with advanced gallbladder cancer. From December, 1993 to June, 1998, 13 patients with advanced gallbladder cancer were treated with low-dose FP therapy. Patients were eligible for this study if they had a bidimensionally measurable tumor. 5-FU (160 mg/m2/day) was continuously infused over 24 hours using an implantable port, and CDDP (3 mg/m2/day) was infused for one hour. The administration schedule consisted of 5-FU for 7 consecutive days and CDDP for 5 days followed by a 2-day rest, each for four weeks according to response and tolerance. Low-dose FP therapy was given to 12 patients (92.3%). The response rate was 66.7% and the median survival time was 151 days. The regimen was tolerable, with the most common toxicity being nausea (38.5%). There were no severe side effects except for one patient who suffered from grade 3 nausea. We conclude that low-dose FP therapy may be useful as a palliative chemotherapy for cases of advanced gallbladder cancer.     

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.     

Limited Efficacy of Cisplatin,UFT and Hydroxyurea Treatment in a Retrospective Evaluation of Patients with Metastatic Gastric Cancer

Background: Most gastric cancer cases are diagnosed at advanced stage and the prognosis is therefore poor.Combination chemotherapy regimens like FAM, FAMTX, ECF, ELF are recommended in advanced gastriccancer. Of particular interest is the HLFP protocol (hydroxyurea, leucovorin, 5-FU, cisplatin) which is reportedto give good response rates. In the present study we evaluated the efficacy of oral UFT instead of 5-FU andleucovorin. Methods: We retrospectively evaluated the efficacy of cisplatin, UFT, and hydroxyurea in combinationin 14 patients with metastatic gastric cancer. Patients with brain metastasis were excluded. The doses of agentswere: oral hydroxyurea 1.5 g/day on days 1-3; cisplatin 80 mg/m2 infusion on day 1 for two hours; and UFTcapsule 400 mg/day dose on days 1 to 14. Results: The results were progressive disease in 8 (57%) patients,stable disease in 2 (17%) patients and partial response in 1 (7%) patient. The overall survival was 7.9 months (3-15), progression free survival was 3.4 (1-7) months. Conclusions: Due to high toxicity and low response rates,cisplatin, UFT and hydroxyurea combination demonstrated limited activity against gastric cancer and was notfound to be effective for the treatment of advanced gastric cancer.     

多西紫杉醇联合奥沙利铂和5-氟尿嘧啶双周方案治疗晚期胃癌的初步研究

目的 探讨多西紫杉醇(DOC)联合奥沙利铂(L-OHP)和5-氟尿嘧啶(5-Fu)的DOF双周方案对晚期胃癌的临床疗效和毒副反应.方法 37例晚期胃癌患者均行锁骨下深静脉穿刺或外周肘正中静脉穿刺,置入单腔输液导管,经电脑输液泵控制5-Fu的输液速度.DOC 35 mg/m2, 静脉滴注1 h,第1天;L-OHP 85 mg/m2,静脉滴注2 h,第1天;甲酰四氢叶酸(LV) 200 mg/m2,静脉滴注2 h,第1天;5-Fu 1500 mg/m2,持续静脉滴注48 h,第1～2天.14 d为1个周期,至少应用3个周期进行疗效评估.结果 全组37例均可评价疗效,总有效率为67.6%,其中完全缓解率为27.0%,部分缓解率为40.5%.至肿瘤进展时间为9.2个月,中位生存期为13.7个月.在初次化疗的11例患者中,有效率为81.8%;在既往接受过化疗的26例患者中,有效率为61.5%.主要剂量限制性毒性反应为骨髓功能抑制,其中Ⅲ～Ⅳ度白细胞下降率为29.7%,无治疗相关性死亡. 结论 DOF双周方案是晚期胃癌的有效化疗方案,其毒副反应轻微,患者易于耐受,值得进一步研究.     

High-dose leucovorin and 5-FU]

Leucovorin (LV), given intravenously the orally becomes 5, 10-methylene tetrahydrofolate in both cancer and normal cells. FdUMP which is an active metabolite of 5-FU binds tightly to thymidylate synthase in the presence of the cofactor 5, 10-methylene tetrahydrofolate. This interaction leads to potentiate the cytotoxic effect of 5-FU by prolonged inhibition of thymidylate synthase. Clinically, the combination of LV and 5-FU is given parenterally by two schedules; 5 consecutive days schedule and weekly schedule. Five 5 consecutive days-schedule is divided into 2 methods. One is a 200 mg/m2/day of LV by Machover, and the other is 20 mg/m2/day of LV by O'Connell. The weekly schedule is a 2-hour infusion of dl-LV (500 mg/m2) and iv bolus of 5-FU (600 mg/m2), given 1 hour after the beginning of LV infusion by Petrelli. A multicenter cooperative study in Japan was conducted to evaluate the clinical efficacy of LV and 5-FU using the weekly schedule by Petrelli. Response rates were 31.5% and 41.2% against advanced gastric and colorectal cancer respectively. Then, we carried out a randomized early phase II study using 250 mg/m2 of l-LV weekly (similar to the schedule of Petrelli's, armA) and 100 mg/m2 (similar to the schedule of Machover's, arm B) or 10 mg/m2 (similar to the schedule of O'Connell's, arm C) of l-LV for 5 consecutive days against gastric cancer. The response rate was 33.3% in arm A, 24.1% in arm B and no response in arm C. Toxicity was within acceptable limits, Toxic effects included diarrhea, stomatitis, anorexia and myelohypoplasia. Our data suggests that high-dose LV and 5-FU seems to be a very promising combination but, there was no responder using low dose (10 mg/m2) of l-LV schedule against gastric cancer patients.     

紫杉醇和5-氟尿嘧啶/醛氢叶酸双周疗法治疗晚期胃癌的初步报告

背景与目的：已有的Ⅱ期临床研究显示,紫杉醇是治疗晚期胃癌的有效药物,紫杉醇和5-氟尿嘧啶(5-fluorouracil,5-Fu)联合化疗治疗晚期胃癌疗效好、不良反应轻。本研究拟观察应用紫杉醇和5-FU／醛氢叶酸(leucovorin,LV)双周疗法治疗晚期胃癌的疗效及不良反应。方法：选取病理检查证实的晚期胃癌患者25例,所有患者均有可评价病灶。治疗方案为紫杉醇75mg／m^2,静脉滴注3h;LV200mg／m^2,静脉滴注2h;5-Fu 375mg／m^2,静脉推注10min;5-Fu2．8g／m^2,静脉灌注48h。以上方案每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：经过2个疗程的化疗后,完全缓解(complete remission,CR)率为8％(2／25),部分缓解(partial remission,PR)率60％(15／25),中位缓解期4个月。无治疗相关死亡,主要不良反应为静脉炎、感觉异常和脱发。结论：紫杉醇和5-Fu／LV双周疗法治疗晚期胃癌患者,缓解率较高、不良反应患者可耐受。     

含奥沙利铂方案治疗晚期胃癌的临床观察

背景与目的:体外实验证明奥沙利铂(oxaliplatin,L-OHP)能明显抑制胃癌细胞株的生长,并与绝大多数抗癌药物具有相加或协同细胞毒作用。本研究观察L-OHP联合醛氢叶酸(leucovorin,LV)、5-氟尿嘧啶(5-fluorouracil,5-FU)和足叶乙甙(etoposide,VP-16)作为一线方案治疗晚期胃癌的疗效和毒性,并与传统化疗方案进行对比。方法:采用非随机分组方法将48例晚期胃癌患者分为两组,即L-OHP+LV+5-Fu+Vp-16方案组(治疗组)25例和DDP+LV+5-Fu+Vp-16方案组(对照组)23例。L-OHP135mg/m2,静滴,第1天(对照组则为DDP20mg,静滴,第1～5天);LV200mg,静滴,第1～5天;5-FU500mg/m2,静滴,维持6h,第1～5天;VP-16100mg,静滴,第1～5天。3～4周为1疗程。结果:治疗组有效率64.0%(16/25),对照组有效率34.8%(8/23),治疗组有效率高于对照组,两组差异有显著性(P<0.05,χ2检验)。治疗组患者的中位生存期为11.5个月,1年生存率为45.6%;对照组患者的中位生存期为10.5个月,1年生存率为36.5%,治疗组中位生存期、1年生存率均高于对照组,但无统计学意义(生存期P>0.05,log-rank检验)。治疗组周围感觉神经症状的发生率较对照组高(P<0.05,秩和检验),恶心、呕吐的发生率较对照组低(P<0.05,秩和检验),其余不良反应两组之间无显著性差异。结论:初步观察L-OHP+V     

Paclitaxel and leucovorin-modulated infusional 5-fluorouracil combination chemotherapy for metastatic gastric cancer

As no standard chemotherapy regimen has been established for advanced gastric cancer, this study sought to evaluate the efficacy and safety of combination chemotherapy that included paclitaxel and leucovorin (LV)-modulated infusional 5-fluorouracil (5-FU) in metastatic gastric cancer. Patients received a three-hour infusion of 175 mg/m2 of paclitaxel on day 1. A bolus of 20 mg/m2 of LV was then administered, followed by a 24-h infusion of 1,000 mg/m2 of 5-FU on days 1 through 3. The treatment cycle was re-peated every 3 weeks until disease progression. Response evaluation was performed according to the RECIST criteria, with toxicity determined by NCI-CTC (version 2.0). A total of 66 patients, including 21 (31.8%) with a history of prior chemotherapy, were enrolled. Fifteen (71.4%) of the 21 patients with prior chemotherapy received prolonged infusional 5-FU. In the 56 evaluable patients (37 in the chemotherapy-na?ve group and 19 in the prior chemotherapy group), tumor responses according to prior exposure to chemotherapy were as follows: 17 (45.9%) partial response (PR), 6 (16.2%) stable disease (SD) and 14 (37.8%) progressive disease (PD) in the chemotherapy-na?ve group; 1 (7.1%) complete response, 3 (15.8%) PRs, 8 (42.1%) SDs and 7 (36.8%) PDs in the prior chemotherapy group. The overall median response duration was 20 weeks (range, 8-61 weeks), with a median progression-free survival of 20 weeks [95% confidence interval (CI), 13.4-26.6 weeks] and 12 weeks (95% CI, 5.7-18.3 weeks) in the chemotherapy-na?ve and prior chemotherapy groups, respectively. The median overall survival was 48 weeks (95% CI, 38-58 weeks) in the chemotherapy-na?ve group and 28 weeks (95% CI, 22-34 weeks) in the prior chemotherapy group. The most frequent grade III/IV toxicity was neutro-penia. Non-hematological toxicity of grade III/IV was rare. Paclitaxel in combination with 5-FU/LV is clinically beneficial for patients with advanced gastric cancer and is a feasible salvage regimen for 5-FU-refractory gastric cancer patients.     

A simplified regimen of weekly high dose 5-fluorouracil and leucovorin as a 24-hour infusion in patients with advanced colorectal carcinoma

BACKGROUND: Reports of in vitro experiments in colorectal carcinoma cells suggest that prolonged cellular exposure to 5-fluorouracil (5-FU) combined with relatively low concentrations of leucovorin (LV) provides optimal enhancement of 5-FU efficacy. In this study, a simplified regimen of weekly 24-hour infusion of high dose 5-FU combined with a relatively low dose of LV was used to treat patients with advanced colorectal carcinoma. METHODS: Thirty-six patients with advanced colorectal carcinoma received 5-FU, 2600 mg/m2, admixed with LV, 100 mg/m2, in a portable infusion pump administered intravenously over a 24-hour period. High dose 5-FU/LV was delivered once a week for 5 consecutive weeks followed by a 1-week recovery period. All patients were assessable for toxicity and response. RESULTS: Two complete responses and 15 partial responses were observed (response rate of 47.2%; 95% confidence interval, 30.1-64.4%). The median response duration was 9.6 months. The median survival and time to progression were 11.9 months and 7.1 months, respectively. The toxicity was mild and acceptable. The major dose-limiting factors were hand-foot syndrome and fatigue. CONCLUSIONS: This simplified regimen of weekly 24-hour continuous infusion of high dose 5-FU/LV is an effective regimen in the treatment of patients with advanced colorectal carcinoma. Further study of the pharmacokinetics of combination therapy with 5-FU and LV as used in this regimen and its correlation with response and toxicity is warranted.     

氟尿嘧啶/亚叶酸钙+紫杉醇联合化疗双周方案治疗晚期胃癌

背景与目的：近来有临床研究显示紫杉醇(paclitaxel,PTX)可用于治疗胃癌,与5．氟尿嘧啶(5-fluorouracil,5-FU)联合治疗晚期胃癌疗效显著,不良反应轻。本研究观察5-Fu／亚叶酸钙(1eueovorin,CF) PTX联合化疗双周方案治疗晚期胃癌的临床疗效和不良反应。方法：采用高剂量5-FU／CF PTX深静脉输注方案(CF 200mg／m^2,静滴2小时,第1天;5-FU 500mg／m^2,静脉推注,第1天;5-FU 1500mg／m^2,静滴46小时;PTX90mg／m^2,静脉输注3小时,第1天),化疗方案以每两周为1周期,重复4周期后评定疗效。结果：全组20例均可评价疗效,总有效率为65．0％(13／20),其中完全缓解(CR)率为10.0％(2／20),部分缓解率为55．0％(11／20)。无治疗相关死亡,主要不良反应为口腔炎、手足综合征和脱发。结论：5-FU／CF PTX联合化疗双周方案治疗晚期胃癌缓解率较高、不良反应可耐受,是治疗晚期胃癌安全有效的化疗方案。     

Treatment of advanced gastric cancer with etoposide,folinic acid,and fluorouracil in the clinical setting: efficacy of therapy and value of serum tumor markers

The combination of etoposide, folinic acid, and 5-fluorouracil (5-FU) (ELF regimen) has been proved to be an active chemotherapy in patients with advanced gastric cancer. The aim of this study was to confirm the efficacy in the clinical setting and to correlate response with different parameters like serum tumor markers. We treated 60 patients with advanced gastric cancer with 120 mg/m² etoposide, 300 mg/m² folinic acid, and 500 mg/m² 5-FU, on d 1–3. The cycle was repeated on d 21. Objective response was obtained in 23% of all patients with measurable disease. Stable disease was obtained in 37%. The tumor-growth-control rate in patients with proximal carcinoma was significantly higher than in those with distal carcinoma (85% vs 48%, p=0.04). Median survival for all patients was 8.0 mo (95% confidence interval [CI] 7.0–8.5). In responsive patients, survival was more than two-fold longer than in patients with progressive disease. The administration of ELF could be performed safely on an outpatient basis. Toxicity was rather mild. The most frequently elevated serum tumor marker was CA 72-4 (55% of the patients). An elevated level of carcinoembryonic antigen before treatment was significantly correlated with progressive disease. A more than two-fold elevation of at least one marker under treatment was significantly correlated to progressive disease (p<0.002). A reduction of at least one marker under treatment was significantly correlated to tumor growth control (p<0.00015). The results of the present trial confirm the efficacy and low toxicity of the ELF regimen in advanced gastric carcinoma. Serum tumor markers proved suitable parameters for assessing response to treatment.