Chemotherapy with Irinothecan, 5-Fluorouracil and Folinic Acid in the First-Line Management of Advanced Colorectal Carcinoma: Retrospective Study

Abstract

Ninety-six patients with chronic bacterial prostatitis (CBP) and evidence of infection were randomized to receive a 4-week oral course of either prulifloxacin (a new fluoroquinolone) 600 mg or levofloxacin 500 mg once daily. They were evaluated with the Meares-Stamey test and the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) at baseline and one week after therapy completion. Patients with microbiological eradication were evaluated again with the Meares-Stamey test 6 months after therapy completion. The microbiological eradication rate was 72.73% for prulifloxacin and 71.11% for levofloxacin (p=0.86) and the reduction in the NIH-CPSI was 10.75 and 10.73, respectively (p=0.98). Safety was comparable, with 18.18% adverse events for prulifloxacin and 22.22% for levofloxacin (p=0.79). Thus, a 4-week course of prulifloxacin 600 mg once daily is at least as effective and safe as levofloxacin 500 mg once daily in the treatment of CBP.     

丝裂霉素、5-氟脲嘧啶、顺铂联合治疗晚期胃癌的临床观察

目的探讨性研究晚期胃癌的姑息性联合化疗方案。方法自1992年3月至1996年12月,我们采用丝裂霉素（MMC）、5-氟脲嘧啶（5－Fu）和顺铂（DDP）联合化疗方案治疗晚期胃癌35例。结果近期总有效率（CR＋PR）为68．57％,其中CR8．57％,PR60％;中位生存时间（MST）13．5月;1、2、3、5年生存率分别为82．75％、22．85％、7．62％和7．62％。消化道反应和骨髓抑制轻微,但有一定的心脏毒性反应和相关感染发生。结论本MFP方案疗效较满意,毒副反应轻,建议在晚期胃癌患者中应用,尤以低分化腺癌者较为适用。     

High and Low Dose Folinic Acid, 5-Fluorouracil Bolus and Continuous Infusion for Poor-Prognosis Patients with Advanced Colorectal Carcinoma

Objective: Evaluation and assessment of response rate, duration and toxicity in patients subjected to 5-FUbased chemotherapy. Background: The therapeutic ratio shifts with different 5FU/LV regimens and none yetserve as the internationally accepted Gold Standard . A bimonthly regimen of high dose leucovorin is reportedto be less toxic and more effective than monthly low dose regimens. We here compare therapeutic responses andsurvival benefit of the two regimens in poor prognosis patients with advanced colorectal carcinoma. Patients andMethods: A total of 35 patients with histologically confirmed colorectal carcinoma were subjected to de Gramontand Mayo Clinic regimen. Nineteen patients were treated with high dose folinic acid (200 mg/m2), glucose 5%,5-FU (400 mg/m2) and 22 hr. CIV (600 mg/m2) for two consecutive days every two weeks. These patients hadfailed responses to previous chemotherapy and were above sixty years of age with poor general status. Sixteenpatients (six below 60 years) with progressive disease were subjected to low dose folinic acid (20 mg/m2)for fivedays, 5FU(425 mg/m2) injection bolus for 5 days, every five weeks. An initial evaluation was made in sixty daysand responders were reevaluated at sixty days interval or earlier in case of clinical impairment. Based on positiveprognosis, the therapy was continued. Evaluation of treatment response was made on the basis of WHO criteria.Results: The response rate was 44% in thirty four evaluable patients, with 4 complete responses (11.8%) and 11(32.4%) partial responses. The two schedules were well tolerated, whereas, mild toxicity without WHO Grade≥2 events was assessed. The response duration was extended (12 months) in a few patients with age above sixtyyears treated by high dose bimonthly regimen of 5FU/LV. Conclusion: The regimens are safe and effective inadvanced colorectal carcinoma patients with poor general status.     

Retrospective Comparison of Two Different Schedules of Irinotecan, 5-Fluorouracil and Folinic Acid in Previously Untreated Patients with Advanced Colorectal Carcinoma: A Single Institution Experience

Abstract

Purpose: To compare efficacy and tolerability of weekly irinotecan combined with 5-fluorouracil (5-FU) bolus and folinic acid (FA) regimen (IFL) versus biweekly irinotecan with infusional 5-FU and FA (FOLFIRI) in patients (pts) with advanced stage colorectal cancer.

Patients and Methods: Treatments outcome of 86 pts (IFL - 38 pts, FOLFIRI - 48 pts) was evaluated. Chemotherapy regimens were as follows: IFL - intravenous (i.v.) infusion irinotecan 125 mg/m² over 90 min and 5-FU 500 mg/m² preceded by FA 20 mg/m² both given by i.v. bolus injection, all repeated on days 1, 8, 15 and 22 every 6 weeks; FOLFIRI - i.v. irinotecan 180 mg/m² on days 1 and 15 with subsequent FA 200 mg/m² administered as a 2-hour infusion and i.v. bolus injection of 400 mg/m² 5-FU immediately followed by 22-hour i.v. infusion of 600 mg/m² 5-FU on days 1, 2, 15 and 16 every 4 weeks. Treatment continued until disease progression or unacceptable toxicity.

Results: A total of 152 (mean - 4) IFL cycles and 328 (mean - 6) FOLFIRI cycles were administered. Average dose intensity was 0.8 and 0.78 respectively. Toxicities were mild and manageable for both regimens evaluated. Overall response rate was 36.8% in IFL arm and 44.7 % in FOLFIRI arm. At the median follow-up of 16 months in IFL arm and 14 months in FOPFIRI arm the two year survival was 38% and 45%, the median survival was 18 months and 21.5 months, and the median progression free survival was 6 months and 9.4 months respectively.

Conclusions: In our experience, both IFL and FOLFIRI regimens have acceptable toxicity at a similar level of dose intensity. Compared to IFL, FOLFIRI seems to improve progression-free survival.     

奥沙利铂联用氟脲嘧啶、亚叶酸钙治疗晚期大肠癌的临床研究

目的　观察奥沙利铂联用氟脲嘧啶、亚叶酸钙治疗晚期大肠癌 (ACRC)的疗效和安全性。方法　收治晚期大肠癌患者 3 0例 ,采用L_OHP 13 0mg/m2 静脉滴注 4hd1 ;CF 2 0 0mg/m2 静脉滴注半小时后 5_Fu 5 0 0mg/m2 静脉滴注 6hd1～ 5,每 3周重复。结果　部分缓解 (PR) 9例 ,稳定 (SD) 8例 ,进展 (PD) 8例 ,总有效率 3 6%。毒性反应主要为感觉神经毒性 ( 90 %) ,其次为恶心呕吐 ( 60 %)和腹泻 ( 4 6 7%)。骨髓抑制毒性小。结论　L_OHP联合 5_Fu、CF治疗大肠癌疗效肯定 ,耐受性良好 ,值得临床进一步研究     

Phase II Trial of 5-Fluorouracil and High-Dose Folinic Acid in Advanced Renal Cell Cancer

Summary

Fourteen patients with metastatic renal cell carcinoma (RCC) were treated with high-dose folinic acid (HDFA): 200 mg/m² i.v. and 5-fluorouracil (5-FU): 370 mg/m² i.v. for 5 consecutive days every 28 days. Severe oral mucositis (WHO grade III-IV) was experienced by two patients, whereas hematological toxicity was mild. No complete or partial remission was observed. Short-lasting stable disease occurred in 8 patients (median = 5 months, range 2-11). This combination does not need further evualuation in patients with RCC.     

Bimonthly Chemotherapy with Oxaliplatin,Irinotecan, Infusional 5-Fluorouracil/Folinic Acid in Patients with Metastatic Colorectal Cancer Pretreated with Irinotecan- or Oxaliplatin-Based Chemotherapy

Abstract

This study was conducted to assess the tolerability and efficacy of a ternary bi-monthly irinotecan (CPT-11) - oxaliplatin (OHP) - infusional 5-fluorouracil (5-FU)/folinic acid (FA) combination in advanced colorectal cancer patients who had received prior CPT-11 and/or OHP-based chemotherapy regimen. Colorectal cancer patients were given bimonthly CPT-11 as a 90-min infusion, followed by OHP (85 mg/m²), FA (200 mg/m²) 2-h infusions and 5-FU (48-h infusion). CPT-11 and 5-FU doses were escalated as reported below. 26 patients were recruited. Fourteen patients had received a prior CPT-11-, 6 patients a prior OHP-based chemotherapy regimen and 6 patients both regimens. Three dose levels were investigated: CPT-11 100, 120 and 140 mg/m² and 5-FU 1500, 1800 and 2100 mg/m² in 6, 12 and 8 patients, respectively. All patients were evaluable for toxicity, 24 for antitumor activity. At all dose levels toxicity was ac-ceptable. Grade 4 toxicity occurred in two patients only (neutropenia in one case and stomatitis in another one, 3.8%). Grade 3 toxicities included nausea and vomiting (34.6%), asthenia (26.9%), neurosensory toxicity (15.4%), neutropenia (3.8%) and di-arrhea (3.8%). Hematological toxicity was infrequent and generally mild. At the third dose level, a higher, although not significantly different incidence of hematological and neurosensory toxicity (both occurring in 62.5% of cases, all grades) was observed compared to the other two, while nausea and vomiting were significantly less frequent (37.5% vs 100%). Overall, we observed 2 complete responses, 9 partial responses (OR 45.8%), 8 stable disease (33.3%), and 5 disease progression (20.8%). Median overall survival was 18 months and median time-to-progression 5.5 months. This combination showed moderate toxicity and promising antitumor activity in CPT-11 and/or OHP pretreated colorectal cancer patients. The second dose level using CPT-11 at 120 mg/m² and 5-FU at 1800 mg/m² is recommended for further phase II studies in this patient population.     

Retrospective Comparison of Single-Agent Chemotherapy with Weekly 5-Fluorouracil or Weekly Irinotecan in Previously Treated Patients with Metastatic Colorectal Cancer

Abstract

This study is a retrospective analysis of response, toxicity and freedom from progression of two single-agent chemotherapy regimens in patients with previously treated metastatic colorectal cancer. Thirty-five patients with histological-ly confirmed measurable metastatic colorectal cancer received chemotherapy after failure of first-line 5-fluorouracil (5-FU) and leucovorin treatment. The median age was 61 years. Twenty-seven patients had liver metastases, 6 had local recurrence, 1 had retroperitoneal lymph node metastases and 1 had lung metastases. Eighteen patients received weekly 2600 mg/m² 5-FU and 17 patients received weekly 125 mg/m² irinotecan (CPT-11). Treatment was given until disease progression. Total number of cycles was 202 for 5-FU and 248 for CPT-11. The relative dose intensity was 1.0 for 5-FU and 0.84 for CPT-11. No grade 3-4 toxicity was registered in patients who received 5-FU. Grade 3- 4 toxicity rates were as follows in those who received CPT-11: vomiting 1 (5.9%) patient in 1 cycle, diarrhea 3 (17.7%) patients in 3 cycles and neutropenia in 3 (17.7%) patients in 3 cycles. No patients manifested febrile neutropenia. Two patients (11.8%) needed hospital admission because of toxicity: 1 for vomiting and 1 for diarrhea. No objective responses were observed in the 5-FU group of patients. Three patients (17.6%) who received CPT-11, achieved partial response with a median duration of 8 months. Stable disease was registered in 3 (17.6%) and 9 (52.9%) patients in 5-FU and CPT-11 groups respectively (p=0.05). Median time to progression was 3.3 months for patients who received 5-FU and 4.2 months for those treated with CPT-11 (not significant). One-year survival was 22.2% and 54.3% respectively (p=0.05).     

国产草酸铂联合氟尿嘧啶及甲酰四氢叶酸钙治疗胃肠癌近期疗效分析

目的 :观察国产草酸铂 (L OHP)联合氟尿嘧啶 (5 FU)、甲酰四氢叶酸钙 (CF)治疗晚期胃癌、大肠癌的疗效。方法 :LFP方案L OHP 130mg m2 ,静脉滴入 ,d1 ;CF 10 0mg m2 ,静脉滴入 ,d1 ～d5;5 FU5 0 0mg m2 ,静脉滴入 ,4～ 6h ,d1 ～d5(5 FU后用 ) ,2 1d为 1个周期。结果 :全组CR 1例 ,PR 12例 ,SD14例 ,PD 5例 ,总有效率 4 0 6 %。初治有效率 4 5 4 % ,复治有效率 38 1% ;胃癌与大肠癌有效率分别为4 1 7%和 37 5 %。主要不良反应为消化道反应及外周神经毒性。结论 :L OHP联合 5 FU、CF方案疗效肯定 ,经济实用 ,毒性可耐受     

Adjuvant Chemotherapy with Mitomycin C, and with a Multi-drug Combination of Mitomycin C, 5-Fluorouracil and Cytosine Arabinoside after Curative Resection of Gastric Cancer

In an attempt to evaluate the adjuvant effect of mitomycin C(MMC) and a combination of MMC, 5-fluorouracil (5-Fu) and cytosinearabinoside (Ara-C) after curative resection of stomach carcinoma,126 cases were entered into an adjuvant chemotherapy program.The patients were divided into three groups randomly. GroupA (42 patients) received 0.08 mg of MMC per kg intravenouslytwice a week for five weeks. Group B (40 patients) receiveda combination of 0.04 mg of MMC, 5 mg of 5-Fu and 0.4 mg ofAra-C per kg intravenously twice a week for five weeks. GroupC (38 patients) received no additional therapy, and served asthe control. Two patients were later eliminated from group Band four from group C as a result of violation of the protocols.There were no deaths from the drugs, but frequent liver dysfunctionwas observed during chemotherapy as a result of toxic effectson the liver under the influence of anesthesia and surgicalintervention. The five year survival in the two treatment groups(A and B) was 64.3% and 66.9%, respectively, compared to 50.0%in the control group. The difference in survival between groupsB and C was statistically significant (P<0.05). That betweengroups A and C was not significant, mainly because of the smallnumber of cases. In relation to a variety of prognostic factors,the adjuvant effect of the chemotherapy was manifest among patientswith moderately advanced disease rather than those with earlystage disease.     

Cisplatinum in Combination with 5-Fluorouracil and Citrovorum Factor in the Treatment of Advanced Colorectal Carcinoma

A phase 11 trial of citrovorum factor, 500 mg/m²/week, plus 5-fluorouracil, 400 mg/m²/week on day 1, and cisplatin, 20 mglm²lweek on day 2, was carried out in a group of 40 patients with metastatic colorectal carcinoma. A partial response with a mean duration of 8.4+ months was achieved in 24% of patients, a minimal response with a mean duration of 5.4 months was obtained in 6% of patients, and a stabilization of 6.2 months was achieved in 41%. Ten patients (29%) progressed. A 38% partial response rate was seen in patients with advanced rectal carcinoma, whereas no response was obtained in patients with colon cancer. Interestingly, 5 partial responses were seen in 12 patients pretreated with 5-fluorouracil. The overall survival was 9.8+ months. The mean survival of patients who achieved a partial response was 12.0+ months, whereas patients who progressed survived a mean of 6.6+ months. Patients with colon cancer had a mean survival of 8.1 + months, and those with rectal cancer survived a mean of 11A + months. This difference was not statistically significant. The treatment was generally very well tolerated, with patients showing mostly grade 1-2 gastrointestinal and Ior hematological toxicity.     

Double Modulation of 5-Fluorouracil in the Treatment of Advanced Colorectal Carcinoma: Report of a Trial with Sequential Methotrexate, Intravenous (Loading Dose) Folinic Acid, 5-Fluorouracil, and a Literature Review

5-Fluorouracil (5-FU) modulation with either folinic acid (FA) or methotrexate (MTX) has improved 5-FU's potential cytoreductivity. We combined MTX and FA with 5-FU to further augment 5-FU's cytoreductivity. Patients (n = 34) with advanced colorectal carcinoma were first given intravenous MTX (escalated from 30 mg/m2 to 70 mg/m²). FA (100 mg/m²) was infused 17-24 hr later, followed by 5-FU (600 mg/m²). Oral rescue doses of FA were begun 24 hr after MTX. Patients were treated every 2 weeks. No previously treated patient (n = 6) responded. Eight of the remaining 28 (29%) (95% confidence interval, 15-47%) patients achieved a PR. Median survival was 9.3 months. Toxicity (primarily gastrointestinal) necessitated dosage modification in 10 patients (29%). These results, in addition to a literature review, reveal that the manipulation of 5-FU by two modulating agents does not improve the response rate seen with single-agent modulation.     

大剂量醛氢叶酸加5-FU持续48小时滴注方案治疗晚期大肠癌的临床观察

目的：评价大剂量醛氢叶酸加5氟尿嘧啶（5-FU）持续48小时滴注方案治疗晚期大肠癌的客观疗效及毒副反应。方法：对入选的22例晚期大肠癌患者采用大剂量醛氢叶酸加5-FU持续48小时滴注方案进行治疗。结果：22例患者均可进行评价；平均化疗3.1个周期；CR1例，PR7例，NC11例，PD3例，总有效率为36.4%。主要的毒副反应为恶心呕吐，脱发，口腔粘膜炎，骨髓抑制及腹泻，大多为Ⅰ-Ⅱ度反应，经常规对症治疗后均见好转。结论：大剂量醛氢叶酸加5-FU持续48小时滴注为主方案治疗晚期大肠癌疗效较好。毒副反应轻。     

两种不同给药途径的大剂量醛氢叶酸联合5-氟尿嘧啶、顺铂治疗晚期鼻咽癌

目的：对比观察静脉及口服大剂量醛氢叶酸（ HDCF）、 5-氟尿嘧啶（ 5- FU）、顺铂（ DDP）联合化疗对晚期鼻咽癌的临床疗效及安全性。方法： 1997年 1月至 1999年 12月间, 53例经病理证实的晚期鼻咽癌患者,非随机分为 PFL1组 28例（按静脉 HDCF/5- FU＋ DDP方案化疗）, PFL2组 25例（按口服 HDCF/5- FU＋ DDP方案化疗）。结果： PFL1组完全缓解 (CR)率、有效率分别为 17.9％、 64.3％;所有病人随访至 1999年 12月止,已死亡 13人,尚存 15人,中位缓解时间 10.5月± 5.24月（ 5～ 21月）,中位生存时间 12.5月± 5.13月（ 4～ 35月）。 PFL2组其 CR率、有效率分别为 16％、 56％。,已死亡 14人,尚存 11人,中位缓解时间 9.3月± 3.10月（ 4～ 28月）,中位生存时间 11.2月± 3.66月（ 4～ 28月）。两组 CR率、有效率、中位缓解时间、中位生存时间均无显著性差异（ P >0.05）。 PFL1及 PFL2方案化疗均对鼻咽肿物、颈部或腹部淋巴结转移、肺转移效果较好,对骨转移虽客观缓解率不高,但止痛效果较好,对肝转移效果较差。两方案的主要毒性反应均为白细胞下降、恶心、呕吐、口腔炎等,其毒性反应相似（ P >0.05）, PFL1组静脉炎（ P< 0.05）、脱发、色素沉着更多见（ P< 0.01）。结论：静脉及口服 H     

Two-Week Combination Chemotherapy with Gemcitabine,High-Dose Folinic Acid and 5 Fluorouracil (GEMFUFOL) as First-Line Treatment of Metastatic Biliary Tract Cancers

Background: The aim of this study was to evaluate the efficacy and tolerability of a gemcitabine, 5-fluorouraciland leucovorin (GEMFUFOL) chemotherapy regimen as first line treatment of metastatic biliary tract cancer.Materials and Methods: All patients received folinic acid 400 mg/m2 on day 1, 5-fluorouracil bolus 400 mg/m2 on day 1, IV infusion of 5-fluorouracil 2400 mg/m2 over 46 hours, and gemcitabine 1250 mg/m2 on day 1.Results: A total of 29 patients with metastatic biliary tract cancer received GEMFUFOL regimen as the firstlinetreatment. The mean follow-up was 22.1 months (95%CI, 12.5-31.8). One patient (3.4%) achieved completeresponse, 5 (17.2%) had partial response, and 4 (13.8%) had stable disease. The median progression-free survivalwas 3.3 months (95%CI, 2.9-3.7), and the median overall survival was 8.8 months (95%CI, 3.5-14). The 1-yearand 2-year survival rates were 58.6% and 30%, respectively. Grade 3 and 4 toxicity included neutropenia in4 patients (13.7%), thrombocytopenia in 2 (6.8%), anemia in 2 (6.8%), and alopecia in 1 (3.4%). Two patients(6.8%) developed febrile neutropenia. A dose reduction was achieved in 8 patients (27.6%) while 5 patientshad extended-interval dosage (17.2%) for toxicity. Conclusions: The GEMFUFOL chemotherapy regimen wasgenerally efficacious and tolerable as a first-line treatment of metastatic biliary tract cancer.     

Combination Chemotherapy of 5-Fluorouracil,Epidoxorubicin and Mitomycin C in the Palliative Treatment of Locally Advanced and/or Metastatic Adenocarcinoma of the Stomach

Summary

Thirty-seven consecutive patients with advanced and/or metastatic gastric adenocarcinoma received a combination of 5-fluorouracil 600 mg/m² on days 1, 8, 29, 36; epidoxorubicin 75 mg/m² i.v. on days 1, 29; mitomycin C 10 mg/m² i.v. on day 1. This cycle was repeated every 8 weeks. Out of a total of 34 evaluable patients, 2 (5.8%) had a complete response and 7 (20.6%) had a partial response with an overall median duration of 40 weeks (range 20-128). The median survival of responding patients was not reached after a mean follow-up of 76 weeks, while that of patients with no change and progressive disease was reached at 36 and 13 weeks respectively.

Treatment was generally well tolerated with hematological and gastrointestinal toxicities being the major side-effects. Despite the use of epidoxorubicin 75 mg/m², the 26.4% (95% confidence limits 16-36%) objective response rate is not satisfactory. Evaluation of more aggressive protocols is strongly recommended within the limits of controlled trials.     

Sequential Methotrexate and 5-Fluorouracil as Second-Line Chemotherapy for Advanced Colorectal Cancer Patients Pretreated with 5-Fluorouracil and Leucovorin: a GISCAD Study

Abstract

The biochemical modulation of 5-fluorouracil (5-FU) by means of methotrexate (MTX) and 6-S leucovorin (LV) seems mainly directed at two different intracellular targets, supporting the hypothesis of possible non-cross resistance between these two methods of 5-FU potentia-tion. Thirty-one patients, all previously treated with 5-FU and LV for advanced colorectal cancer (ACC), were treated with MTX=200 mg/m² iv day 1 and 5-FU 600 mg/m² day 2 with 6-S LV 10 mg/m² po q 6 h X 6 starting 24 h after MTX, repeated every 2 weeks. Of 30 eva-luable patients, 2 Partial Remissions (PR) were achieved (Response Rate=6.6%; 95% Confidence Interval 0%-14%). Eight patients had disease stabilization (SD). The overall median survival was 5 months (range 1-11). No WHO grade III-IV toxicities were reported. Despite the good tolerability, this combination of MTX, 5-FU and LV rescue has minimal activity in ACC after the failure of 5FU+LV-based chemotherapy.     

Is the Combination of 5-Fluorouracil and Folinic Acid Effective in Advanced Gastric Carcinoma? Results of a pilot study and review of the literature

Summary

The main purpose of this trial was to investigate the activity of a less toxic regimen in patients with advanced gastric carcinoma regarding response rate and survival. We report on a pilot study of 20 patients treated with the combination of 5-fIuorouracil and folinic acid. 5-fluorouracil was administered at a daily dose of 450 mg/m² followed by folinic acid 200 mg/m² for four consecutive days every four weeks. The overall response rate was 15% with one complete and two partial responders. The median duration of response was 11, 10 and 10 months respectively. The median survival of all patients was 9 months. Toxicity was mild and consisted primarily of diarrhea. Stomatitis and myelosuppression occurred rarely.

In conclusion, the combination of 5-fluorouracil and folinic acid has moderate activity in gastric cancer, while median survival appears similar to the other more intensive regimens. The combination is very well tolerated with minimal toxicity. A detailed review of the literature regarding the effectiveness of the above regimens on response rate, overall survival and toxicity is also presented.     

Combined Epirubicin, 5-Fluorouracil and Folinic Acid vs No Treatment for Patients with Advanced Pancreatic Cancer: A Prospective Comparative Study

Abstract

The combination of 5-fluorouracil (5-FU) and folinic acid (FA) has demonstrated activity in most gastrointestinal tumors. The addition of epirubicin (EPI) may increase the efficacy of the combination for cancers of the upper gastrointestinal tract, such as advanced pancreatic cancer. We examined two groups of patients, explaining the potential benefits and limitations of therapy, and those patients who agreed to undergo chemotherapy formed Group A and the remaining formed Group B. Therefore, the study was a non-randomized prospective comparison between patients receiving chemotherapy and those offered the best supportive care. Group A consisted of 42 patients; 19 underwent Roux-en-Y operation, and 23 were inoperable. Group B consisted of 48 patients who refused chemotherapy; 18 underwent Roux-en-Y operation, and 30 were considered inoperable. Chemotherapy consisted of FA 200 mg/m²/day, 5-FU 600 mg/m²/day both for 5 days, and EPI 35 mg/m²/day before FA-5-FU administration on days 1 and 2, every 28 days. All patients were evaluable for response and toxicity. Objective tumor responses (partial responses) in Group A were seen in 8 patients (19%) (6 women and 2 men), and 6 (14%) had stable disease. The estimated median survival was 27.6 weeks (mean 27.5) for Group A and 22.5 weeks (mean 24) (p=0.01) for Group B. From the onset of therapy, median duration of response was 16.6 weeks and median time to progression 11.8 weeks in Group A. Toxicity consisted primarily of myelosuppression, nausea and vomiting, diarrhea, alopecia, and mucositis. In Group A 12/42 patients became free from pain for a median duration of 10 months, 14/42 had improved appetite, and 15/42 had improved performance status in comparison to Group B, where no patients had improved performance status or symptoms. We conclude that the combination of EPI+FA+5-FU has moderate activity and increased toxicity in the treatment of advanced pancreatic cancer.