Biochemical modulation of bolus fluorouracil by PALA in patients with advanced colorectal cancer.

1992 ◽  
Vol 10 (5) ◽  
pp. 747-752 ◽  
Author(s):  
N Kemeny ◽  
J A Conti ◽  
K Seiter ◽  
D Niedzwiecki ◽  
J Botet ◽  
...  
Keyword(s):  
Colorectal Carcinoma ◽  
Median Survival ◽  
Low Dose ◽  
Complete Response ◽  
Albumin Level ◽  
Phase Iii ◽  
Biochemical Modulation ◽  
Hematologic Toxicity ◽  
Synthesis Inhibitor ◽  
Pyrimidine Synthesis

PURPOSE N-(phosphonacetyl)-L-aspartic acid (PALA) is a pyrimidine synthesis inhibitor that modulates fluorouracil (FU) cytotoxicity. Two previous studies of patients with colorectal carcinoma documented complete response (CR) and partial response (PR) rates of 40% and 43% using weekly low-dose PALA followed by a 24-hour FU infusion. We investigated whether comparable results could be obtained with biochemical modulation by low-dose PALA using bolus instead of infusional FU. PATIENTS AND METHODS Forty-five patients without prior chemotherapy who had advanced colorectal carcinoma were treated with PALA 250 mg/m2 followed 24 hours later by bolus FU at three dose levels, 600, 700, 800 mg/m2, repeated weekly for 6 weeks followed by a 2-week break. RESULTS The CR and PR rate was 15 of 43 patients or 35% (95% confidence interval [CI], 21% to 49%), with an overall median survival of 18 months. Grade 3 or 4 diarrhea was the major toxicity observed in 24% of patients receiving FU at 700 mg/m2 and in 43% of patients receiving 800 mg/m2. Hematologic toxicity was observed only with an FU dose of 800 mg/m2, and 29% (four of 14) of patients developed grade 4 leukopenia. We also noted the development of ascites in six patients, mild hyperbilirubinemia in 16 patients, and a decreased albumin level in 22 patients; these abnormalities occurred more frequently in responding patients. CONCLUSIONS The observed response rate, median survival, and toxicity in this study are similar to those obtained with PALA plus infusional FU and with other methods of FU modulation. Larger phase III studies are needed to compare bolus FU/PALA regimens with other PALA and non-PALA-containing combinations. Our future focus will be attenuate this regimen's toxicity while maintaining or improving its response rates and survival.

Combination chemotherapy (5-fluorouracil, methyl-CCNU, mitomycin C) versus 5-fluorouracil alone for advanced previously untreated colorectal carcinoma. A phase III study of the Piedmont Oncology Association.

1986 ◽  
Vol 4 (4) ◽  
pp. 565-570 ◽  
Author(s):  
F Richards ◽  
L D Case ◽  
D R White ◽  
H B Muss ◽  
C L Spurr ◽  
...  
Keyword(s):  
Complete Remission ◽  
Colorectal Carcinoma ◽  
Mitomycin C ◽  
Median Survival ◽  
Partial Remission ◽  
Performance Status ◽  
Normal Liver ◽  
Liver Function Tests ◽  
Phase Iii ◽  
Hematologic Toxicity

One-hundred thirty eligible patients with advanced colorectal carcinoma who had received no prior chemotherapy were randomized to either methyl-CCNU, 70 mg/m2 orally every 6 weeks on day 1, mitomycin C, 10 mg/m2 intravenously every 6 weeks on day 1, and 5-fluorouracil (5-FU), 400 mg/m2 intravenously weekly--(MMF)--or 5-FU, 600 mg/m2 intravenously weekly (5-FU). One hundred twenty-six patients are evaluable for response. Of 62 patients treated with MMF, one (2%) achieved complete remission, and three (5%) attained partial remission. Of 64 patients treated with 5-FU, two (3%) achieved complete remission, and eight (13%) attained partial remission. The median survival for patients receiving MMF was 9.5 months compared with 10.3 months for patients receiving 5-FU. The survival distributions for the two regimens were not significantly different, either unadjusted or adjusted for pretreatment characteristics. Performance status and lactic dehydrogenase (LDH) were both significantly associated with survival. Patients with liver metastases only and normal liver function tests had a median survival of 19.8 months and a 40% response rate. This randomized phase III trial did not show any therapeutic advantage for MMF compared to 5-FU therapy alone in advanced colorectal cancer. In addition, hematologic toxicity was significantly greater with the combination (MMF) regimen.

Phase II trial of uracil and tegafur plus oral leucovorin: an effective oral regimen in the treatment of metastatic colorectal carcinoma.

1994 ◽  
Vol 12 (11) ◽  
pp. 2296-2300 ◽  
Author(s):  
R Pazdur ◽  
Y Lassere ◽  
V Rhodes ◽  
J A Ajani ◽  
S M Sugarman ◽  
...  
Keyword(s):  
Colorectal Carcinoma ◽  
Oral Mucositis ◽  
Rest Period ◽  
Complete Response ◽  
Phase Iii ◽  
Significant Activity ◽  
Metastatic Colorectal Carcinoma ◽  
Oral Regimen ◽  
Phase Iii Study ◽  
Grade 3

PURPOSE To determine the activity and evaluate the toxicity of uracil and tegafur in a 4:1 molar concentration (UFT; Taiho Pharmaceutical Ltd, Tokyo, Japan) plus oral calcium leucovorin in the treatment of patients with advanced colorectal carcinoma. PATIENTS AND METHODS Forty-five patients with advanced, bidimensionally measurable metastatic colorectal carcinoma were enrolled onto the trial. None of the patients had received prior chemotherapy or biologic therapy for advanced disease. Patients received either 350 or 300 mg/m2/d UFT plus 150 mg/d leucovorin administered orally in divided daily doses every 8 hours for 28 days followed by a 7-day rest period. Response was evaluated after two courses of therapy. RESULTS Eighteen patients (three treated at 350 mg/m2/d and 15 at 300 mg/m2/d) had partial responses, and one patient had a complete response (response rate, 42.2%; 95% confidence interval, 28% to 58%). Responses were observed in sites that included liver (n = 18), lung (n = 6), and bone (n = 1). Of seven patients who received 350 mg/m2 UFT, prolonged grade 3 diarrhea developed in five; this resulted in a reduction in the UFT starting dose to 300 mg/m2/d in the remaining 38 patients. Grade 1 or 2 toxic effects included diarrhea, nausea, vomiting, abdominal cramping, anorexia, fatigue, oral mucositis, excessive lacrimation, and rash. Among 38 patients who received the 300-mg/m2/d dose, grade 3 toxic reactions included diarrhea (n = 4), vomiting (n = 2), abdominal cramping (n = 1), and fatigue (n = 2). CONCLUSION UFT 300 mg/m2/d plus oral leucovorin 150 mg/d administered for 28 days demonstrated significant activity against metastatic colorectal carcinoma. This oral regimen was well tolerated and devoid of the neutropenia or significant oral mucositis that complicates intravenous schedules of fluorouracil (5-FU) plus leucovorin. The results of this clinical trial will serve as the basis for a randomized phase III study to compare this oral schedule of UFT plus leucovorin with intravenous 5-FU plus leucovorin to determine the relative efficacy, impact on quality of life, and cost of the two regimens.

scholarly journals The impact of adding low-dose leucovorin to monthly 5-fluorouracil in advanced colorectal carcinoma: Results of a phase III trial

1998 ◽  
Vol 9 (5) ◽  
pp. 535-541 ◽  
Author(s):  
M.M. Borner ◽  
M. Castiglione ◽  
M. Bacchi ◽  
W. Weber ◽  
R. Herrmann ◽  
...  
Keyword(s):  
Colorectal Carcinoma ◽  
Low Dose ◽  
Phase Iii ◽  
Phase Iii Trial ◽  
Advanced Colorectal Carcinoma ◽  
The Impact

A phase II study of celecoxib (C) with irinotecan (I), 5-fluorouracil (F), and leucovorin (L) in patients (pts) with advanced or metastatic colorectal cancer (CRC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3588-3588
Author(s):  
R. E. Sanborn ◽  
H. Lenz ◽  
D. G. Haller ◽  
A. B. Benson ◽  
T. Dragovich ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Phase Ii ◽  
Low Dose ◽  
Locally Advanced ◽  
Phase Iii ◽  
Hematologic Toxicity ◽  
Cardiac Events ◽  
Vascular Toxicity ◽  
Cox 2 ◽  
Post Modification

3588 Background: Expression of cyclooxygenase-2 (COX-2), present in most CRC, is associated with a worse prognosis. C, a selective COX-2 inhibitor, has inhibitory effects against CRC which appear at least additive with chemotherapy preclinically. A multi-institutional phase II trial was conducted to evaluate C plus standard IFL as first-line treatment for pts with incurable CRC. Methods: C 400mg po BID starting Day #1; I 125mg/m2 iv weekly starting Day #15; F 500mg/m2 iv bolus weekly starting Day #15; L 20mg/m2 iv weekly bolus starting Day #15. Patients received IFL for 4 weeks followed by a two-week rest. C was continued during the rest. Pts were treated until disease progression or unacceptable toxicity. Primary endpoint was response with planned sample size of 47 patients. Results: 47 pts were consented and treated. Evaluable pt characteristics: Male/female (no.) = 34/13; mean age = 59.7; ECOG PS 0/1/2 (no.) = 31/14/2; cancer stage locally-advanced/distant/unknown (no.) = 10/28/9. Due to concerns of risk of excess cardiovascular (CV) toxicity the protocol was amended halfway through enrollment to exclude pts with PS 2, and to require low-dose aspirin (ASA) for pts at high risk for CV events. Pre-and post-modification (mod) results are shown in the table . In general hematologic toxicity was moderate. Non-hematologic toxicity was mostly gastrointestinal, but 25% experienced cardiac or vascular toxicity (1 cardiac arrest, 1 MI, 1 CHF, 3 arrhythmias, 2 DVT, 2 CVA, 1 hyper- and 1 hypotension). All cardiac events occurred before modification of the protocol. There was 1 treatment-related death from cardiac arrest. Conclusions: C may be given safely with IFL chemotherapy, if pts are carefully selected. Addition of low-dose ASA may reduce cardiac toxicity. Post-mod TTP and survival for C plus IFL appear superior to historical results for IFL, but a phase III study would be required for confirmation. [Table: see text] [Table: see text]

Survival after sipuleucel-T (SIP-T) and low-dose ipilimumab (IPI) in men with metastatic, progressive, castrate-resistant prostate cancer (M-CRPC).

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 368-368 ◽  
Author(s):  
Justine Ku ◽  
Kirk Wilenius ◽  
Claire Larsen ◽  
Kyle De Guzman ◽  
Steven Yoshinaga ◽  
...  
Keyword(s):  
Median Survival ◽  
Gleason Score ◽  
Low Dose ◽  
Phase Iii ◽  
Combination Methods ◽  
Radium 223 ◽  
Potential Synergy ◽  
Phase Iii Trials ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant

368 Background: Phase III trials evaluating enzalutamide or abiraterone in MP-CRPC prior to docetaxel report a median survival of 35 months. SIP-T functions by stimulating cancer-specific dendritic cells and prolongs survival. IPI showed a borderline survival advantage in a large randomized trial. Thus, there may be potential synergy with SIP-T and IPI (SIPIPI) in combination. Methods: Between April 2013 and April 2014, 9 docetaxel-naive men with MP-CRPC were treated prospectively with SIP-T followed immediately by low-dose IPI 1 mg/kg given for a total of 1 to 3 doses every three weeks. As has been previously published (Immuno Targets and Therapy, March 2017), cancer-specific immunoglobulins (IGS) directed at PA2024 and PAP showed a statistically-significant increase after SIP-T and a further statistically-significant increase, above the level achieved with SIP-T, after IPI. Three patients died from progressive disease after 9, 18, and 20 months. This abstract updates the outcome and survival of the remaining 6 patients. Results: Adverse events from SIPIPI were negligible. For the 9 men, the median age, Gleason score, and number of previous hormonal interventions were 77 years, 8, and 3, respectively. Median baseline PSA and Gleason score were 1.7 and 8, respectively. Eight men had bone metastases and 1 had lymph node metastasis. For the 6 surviving men, median follow-up since SIPIPI is 50.5 months (40-53). Their median PSA as of September 2017 is 5.5 (range: 0.27–18.10). Further treatment since SIPIPI includes abiraterone (4) enzalutamide (5) radium-223 (3) docetaxel (2) cabazitaxel (1) carboplatin (1) pembrolizumab (2) and Olaparib (1). One patient continues with a stable PSA of 0.27 without any further treatment post SIPIPI except SBRT. Conclusions: In this small trial of SIPIPI performed in men with docetaxel-naive MP-CRPC, median survival has now surpassed 4 years and the 6 surviving men still maintain a relatively low median PSA of 5.5. One man continues in durable remission without any further therapy except SBRT administered immediately post IPI.

Phase I Chemotherapy Study of Biochemical Modulation of Folinic Acid and Fluorouracil by Gemcitabine in Patients With Solid Tumor Malignancies

2000 ◽  
Vol 18 (20) ◽  
pp. 3553-3557 ◽  
Author(s):  
S. Madajewicz ◽  
P. Hentschel ◽  
P. Burns ◽  
R. Caruso ◽  
J. Fiore ◽  
...  
Keyword(s):  
Colorectal Carcinoma ◽  
Phase I ◽  
Folinic Acid ◽  
Treatment Options ◽  
Complete Response ◽  
Maximum Tolerated Dose ◽  
Primary Treatment ◽  
Biochemical Modulation ◽  
Steady Rate ◽  
Chemotherapy Study

PURPOSE: This phase I biochemical modulation study evaluated the maximum-tolerated dose (MTD), toxicity, and effectiveness of the combination of folinic acid (FA)/fluorouracil (5-FU) followed by escalated dose levels of gemcitabine (FFG) in patients with advanced solid tumors.PATIENTS AND METHODS: Patients were refractory to primary treatment and/or without effective treatment options. Twenty-eight patients received an intravenous (IV) infusion of FA 100 mg/m2over 1 hour and a 5-FU 450 mg/m2IV bolus in the middle of the FA infusion. After the FA infusion, gemcitabine was administered at a steady rate of infusion of 10 mg/m2/min over initially 30 minutes and with increases of an additional 15 minutes at each given level. One cycle consisted of six weekly treatments followed by a 2-week rest.RESULTS: The MTD of gemcitabine was established at 900 mg/m2given over 90 minutes. Eight patients of 21 with metastatic colorectal cancer achieved responses (one complete response; seven partial responses), for a response rate of 38%. Responses were seen across the gemcitabine doses of 300 to 900 mg/m2. One patient had prior treatment with FA/5-FU for advanced disease. Patients with colorectal carcinoma had a median survival of 18 months, and the patient with lung carcinoma has been alive for 24+ months.CONCLUSION: The combination chemotherapy of FFG was well tolerated and may benefit patients with advanced colorectal carcinoma. A phase II evaluation in this patient population is in progress.

Clinical Outcome of 40 Patients with Higher-Risk Myelodysplastic Syndromes (MDS) after Treatment with Hypomethylating Agents: a Matched-Pairs Analysis

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2687-2687
Author(s):  
Kathrin Nachtkamp ◽  
Corinna Strupp ◽  
Andrea Kuendgen ◽  
Norbert Gattermann ◽  
Rainer Haas ◽  
...  
Keyword(s):  
High Risk ◽  
Survival Time ◽  
Median Survival ◽  
Median Survival Time ◽  
Survival Benefit ◽  
Low Dose ◽  
Phase Iii ◽  
Matched Pairs ◽  
Hypomethylating Agents ◽  
Kaplan Meier

Abstract Introduction: Patients with higher-risk MDS, especially those with an IPSS score of intermediate-2 or high, face a very poor prognosis with a median survival of 12 to 18 months. Allogeneic transplantation as a curative approach is an option for only a small percentage of patients. In phase-III-trials, hypomethylating agents demonstrated a survival benefit for this patient group. In order to validate the use of these compounds in clinical day-to-day practice, we analyzed 40 patients who underwent hypomethylating treatment with either decitabine or 5-azacytidine. Methods: We performed matched-pairs analyses using the Düsseldorf MDS registry (n=3288). Patients with higher-risk MDS (INT-1, INT-2, or high-risk IPSS scores) at the time of treatment with hypomethylating agents (n=40) were compared with higher-risk MDS patients who received best supportive care (BSC) only (n=120) and with higher-risk MDS patients who underwent treatment with low-dose Ara-C (n=35). Patients were matched according to age, gender, WHO type, IPSS score and date of diagnosis. Each patient in the hypomethylating cohort was matched with three patients of the BSC cohort and one patient of the low-dose ara-C cohort. For 5 patients, no adequate match partner of the low-dose ara-C cohort could be assigned. Follow-up for survival was assured by contacting our outpatient department or primary care physician. Results: The distribution of WHO types at time of diagnosis within the decitabine/5-azacytidine cohort was 10 RA/RCMD patients, 9 RAEB I, 16 RAEB II, 2 CMML I and 3 CMML II. Median age was 70 years. 10 patients belonged to the intermediate-1, 11 to the intermediate-2 and 18 patients to the high-risk group according to the IPSS score. In one patient, the IPSS score could not be assessed. All patients had progressed to at least RAEB II when treatment was initiated. 19 patients received decitabine and 21 patients were given 5-azacytidine. Median survival time in the hypomethylating cohort was 28 months, regardless of the type of hypomethylating treatment, compared with 10 months in the BSC cohort. Figure 1 shows the Kaplan Meier curve comparing 40 patients treated with hypomethylating agents with 120 patients who received BSC only (p=0.0026). Median survival time of the low-dose ara-C cohort was 20 months; although 5 patients of the hypomethylating cohort could not be assigned a match partner and therefore had to be withdrawn from the comparison with low-dose ara-C, median survival in the remaining 35 patients of the hypomethylating cohort was still 28 months. Figure 2 shows the Kaplan Meier curve comparing the hypomethylating cohort with the low-dose ara-C cohort (p=0.027). Conclusions: Our data show that higher-risk MDS patients have a substantial survival benefit from treatment with hypomethylating agents as compared to both low-dose ara-C and BSC patients. Hypomethylating agents should be considered to be the treatment of choice in higher-risk MDS patients who are not candidates for allografting. Figure Figure

Phase II Trial of Systemic Continuous Fluorouracil and Subcutaneous Recombinant Interferon Alfa-2b for Treatment of Hepatocellular Carcinoma

2003 ◽  
Vol 21 (3) ◽  
pp. 421-427 ◽  
Author(s):  
Yehuda Z. Patt ◽  
Manal M. Hassan ◽  
Richard D. Lozano ◽  
Thomas D. Brown ◽  
J. Nicolas Vauthey ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Median Survival ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Complete Response ◽  
The United States ◽  
Interferon Alfa ◽  
Hematologic Toxicity ◽  
Recombinant Interferon ◽  
Grade 3

Purpose: Because cirrhosis is extremely common in hepatocellular carcinoma (HCC) in the United States, and it precludes the use of several chemotherapy agents, this phase II trial of fluorouracil (FU) and recombinant interferon alfa-2b (rIFNα2b) in HCC was launched with the assumption that it could be tolerated by cirrhotics. Patients and Methods: Forty-three patients with HCC (34), and fibrolamellar HCC (FLHCC; nine) were treated with continuous intravenous (IV) FU (200 mg/m2/d × 21 every 28 days) and subcutaneous (SC) rIFNα2b (4 million U/m2) three times weekly. Survival was determined in all 43 patients, and response could be assessed in 28 HCC and 8 FLHCC patients. Results: The median ages of the patients were 63.5 and 19 years among HCC and FLHCC patients, respectively. Liver cirrhosis was present among 71% of HCC patients but among none of the FLHCC patients. Nine of 36 (25%; four of 28 [14%] HCC patients; five of eight [62.5%] FLHCC patients) patients in which a response could be assessed had a complete response (CR; one patient with FLHCC and no patients with HCC) or partial response (PR; eight patients [four HCC and four FLHCC patients]). Four HCC patients underwent resection, and two had a histologic CR; one HCC patient with a PR underwent orthotopic liver transplantation. One FLHCC patient also underwent resection without clear margins. Overall median survival was 19.5 months (95% confidence interval [CI], 11.2 to 27.8 months); median survival was 15.5 months (95% CI, 8.5 to 22.5 months) among HCC patients, and that of FLHCC patients was 23.1 months (95% CI, 10.3 to 35.9 months). Overall grade 3 or 4 toxicity included stomatitis (32.6%), fatigue (4.7%), and hematologic toxicity (9.3%). Conclusion: Continuous IV FU and thrice-weekly SC rIFNα2b are an effective treatment, especially for FLHCC, and may have a neoadjuvant role in this disease. This regimen has activity in HCC and can be tolerated even by cirrhotic patients.

Phase II Trial of Cisplatin, Gemcitabine, and Bevacizumab As First-Line Therapy for Metastatic Urothelial Carcinoma: Hoosier Oncology Group GU 04-75

2011 ◽  
Vol 29 (12) ◽  
pp. 1525-1530 ◽  
Author(s):  
Noah M. Hahn ◽  
Walter M. Stadler ◽  
Robin T. Zon ◽  
David Waterhouse ◽  
Joel Picus ◽  
...  
Keyword(s):  
Phase Ii ◽  
Performance Status ◽  
Evaluation Criteria ◽  
Progression Free Survival ◽  
Complete Response ◽  
Phase Iii ◽  
Hematologic Toxicity ◽  
First Line ◽  
Metastatic Urothelial Cancer ◽  
Grade 3

PurposeNovel approaches are needed for patients with metastatic urothelial cancer (UC). This trial assessed the efficacy and toxicity of bevacizumab in combination with cisplatin and gemcitabine (CGB) as first-line treatment for patients with metastatic UC.Patients and MethodsChemotherapy-naive patients with metastatic or unresectable UC received cisplatin 70 mg/m2on day 1, gemcitabine 1,000 to 1,250 mg/m2on days 1 and 8, and bevacizumab 15 mg/kg on day 1, every 21 days.ResultsForty-three patients with performance status of 0 (n = 26) or 1 (n = 17) and median age of 66 years were evaluable for toxicity and response. Grade 3 to 4 hematologic toxicity included neutropenia (35%), thrombocytopenia (12%), anemia (12%), and neutropenic fever (2%). Grade 3 to 5 nonhematologic toxicity included deep vein thrombosis/pulmonary embolism (21%), hemorrhage (7%), cardiac (7%), hypertension (5%), and proteinuria (2%). Three treatment-related deaths (CNS hemorrhage, sudden cardiac death, and aortic dissection) were observed. Best response by Response Evaluation Criteria in Solid Tumors was complete response in eight patients (19%) and partial response in 23 patients (53%), for an overall response rate of 72%. Stable disease lasting ≥ 12 weeks occurred in four patients (9%), and progressive disease occurred in six patients (14%). With a median follow-up of 27.2 months (range, 3.5 to 40.9 months), median progression-free survival (PFS) was 8.2 months (95% CI, 6.8 to 10.3 months) with a median overall survival (OS) time of 19.1 months (95% CI, 12.4 to 22.7 months). The study-defined goal of 50% improvement in PFS was not met.ConclusionCGB demonstrates promising OS and antiangiogenic treatment-related toxicities in the phase II setting of metastatic UC. The full risk/benefit profile of CGB in patients with metastatic UC will be determined by an ongoing phase III intergroup trial.

The modulation of fluorouracil with leucovorin in metastatic colorectal carcinoma: a prospective randomized phase III trial. Gastrointestinal Tumor Study Group.

1989 ◽  
Vol 7 (10) ◽  
pp. 1419-1426 ◽  
Author(s):  
N Petrelli ◽  
H O Douglass ◽  
L Herrera ◽  
D Russell ◽  
D M Stablein ◽  
...  
Keyword(s):  
Colorectal Carcinoma ◽  
Low Dose ◽  
Phase Iii ◽  
High Dose ◽  
Metastatic Colorectal Carcinoma ◽  
Phase Iii Trial ◽  
Severe Diarrhea ◽  
Gastrointestinal Tumor Study Group ◽  
The Impact ◽  
Dose Limiting Toxicity

A total of 343 patients with previously untreated metastatic measurable colorectal carcinoma were studied to evaluate the impact on toxicity, response, and survival of leucovorin-modulated fluorouracil (5-FU). A maximally tolerated intravenous bolus loading course regimen of 5-FU alone (500 mg/m2 x 5 days every 4 weeks with 25 mg/m2 escalation) was compared with a high-dose leucovorin regimen (600 mg/m2 of 5-FU with 500 mg/m2 of leucovorin weekly for 6 weeks with a 2-week rest) and with a similar low-dose leucovorin regimen (600 mg/m2 of 5-FU with 25 mg/m2 of leucovorin weekly for 6 weeks with a 2-week rest). The dose-limiting toxicity for the two 5-FU and leucovorin regimens was gastrointestinal, specifically diarrhea; severe diarrhea was seen frequently, and treatment-related toxicity was implicated in the demise of 11 of the patients (5%). Significant improvements in response rates were observed with a response rate of 33 of 109 (30.3%) on the high-dose leucovorin regimen (P less than .01 v control); 13 of 107 (12.1%) on the 5-FU control; and 21 of 112 (18.8%) on the low-dose leucovorin regimen. A trend toward longer survival in the 5-FU plus high-dose leucovorin regimen was observed. In this study, leucovorin was shown to significantly enhance the therapeutic effect of 5-FU in metastatic colorectal carcinoma.

Sign in / Sign up

Export Citation Format

Share Document