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Decreased Intoxication by Fluorouracil When Slowly Administered in Glucose

Decreased Intoxication by Fluorouracil When Slowly Administered in Glucose Abstract Moderate to severe systemic intoxication resulting from rapid intravenous injection of 5-fluorouracil in cancer chemotherapy has been reduced from an incidence of 50% to 60% to 6% in a series of 83 patients by use of infusions in 5% glucose over 8 hours. Doses of 10 to 25 gm per patient per course have been tolerated with minimal toxic reactions. There was objective palliation of metastases in 27% from drug therapy alone, and in a further 10% by treatment combined with hormonal or x-ray therapy. Avoidance of intoxication by slow intravenous infusion has broadened the opportunities for use of this drug in ambulatory therapy of colorectal, biliary tract, ovarian, and mammary cancer. References 1. Hoffman LaRoche, Inc, Nutley, N. J., Department of Clinical Investigation: Clinical Data Sheet 5-Fluorouracil (RO 2-9757). 2. Lemon, H.M.: Reduction of 5-Fluorouracil Toxicity in Man with Retention of Anticancer Effects, by Prolonged Intravenous Administration in 5% Dextrose , Cancer Chemother Rep 8:97-101 ( (July) ) 1960. 3. Sullivan, R.P., et al: Clinical Effects of Fluorinated Pyrimidines ( 5-Fluorouracil and 5 F Fluoro 2 1 deoxyuridine) , Cancer Chemother Rep 8:77-83 ( (July) ) 1960. 4. Wolberg, W.H., and Curreri, A.R.: Toxicity Studies of 5-Fluorouracil Used as Adjunct to Surgery , Arch Surg (Chicago) 81:244-250, 1960.Crossref 5. Krant, M.J.: Alterations in Administration of Fluorouracil; Experiences with Two-Hour Infusions , Cancer Chemother Rep 15:35-40, 1961. 6. Staley, C.J., et al: Various Methods of Administering 5-Fluorouracil , Cancer Chemother Rep 20:107-112, 1962. 7. Reitemeyer, R.J., and Moertel, C.G.: Comparison of Rapid and Slow Intravenous Methods of Administration of 5-Fluorouracil in Treatment of 100 Patients with Advanced Carcinoma of Large Intestine , Proc Amer Ass Cancer Res 3:353, 1962. 8. Frank, W.; Brennan, J.T.; Lo Presti, J.M.: Preliminary Pharmacologic Observations on Concomitant Use of X-ray and 5-Fluorouracil in Human Malignancies , Cancer Chemother Rep 11:145-146, 1961. 9. Ansfield, F.J., and Currieri, A.R.: Further Clinical Studies with 5-Fluorouracil , J Nat Cancer Inst 22:497-507, 1959. 10. Cornell, G.N., et al: Clinical Experience with 5-Fluorouracil in Treatment of Malignant Disease , Cancer Chemother Rep 9:23-30, 1960. 11. Olson, J.B., and Green, J.R.: Evaluation of 5-Fluorouracil in Treatment of Cancer , J Nat Cancer Inst 25:133-140, 1960. 12. Wilson, W.L.: Chemotherapy of Human Solid Tumors with 5-Fluorouracil , Cancer 13:1230-1239, 1960.Crossref 13. Vaitkevicius, V.K., et al: Clinical Evaluation of Cancer Chemotherapy with 5-Fluorouracil , Cancer 14:131, 1961.Crossref 14. Young, C.W., et al: Clinical Evaluation of 5-Fluorouracil and 5-Fluoro-2-Deoxyuridine in Solid Tumors in Adults, Progress Report , Cancer Chemother Rep 6:17-20 ( (Feb) ) 1960. 15. Gold, G.L., et al: Clinical Study of 5-Fluorouracil , Cancer Res 19:935-939, 1959. 16. Kahler, H., and Van Robertson, W.B.: Hydrogen Ion Concentration of Normal Liver and Hepatic Tumors , J Nat Cancer Inst 3:493, 1947. 17. Ross, W.J.C.: Increased Sensitivity of Walker Tumor Towards Aromatic Nitrogen Mustards Carrying Basic Side Chains Following Glucose Pre-Treatment , Biochem Pharmacol 8:235, 1961.Crossref 18. Heidelberger, C., et al: Studies on Fluorinated Pyrimidines X in vivo Studies on Tumor Resistance , Cancer Res 20:897-902, 1960. 19. Woods, N.W.; Hunter, J.C.; and Burls, D.: Glucose Enhancement of Inhibition by Fluorinated and Normal Pyrimidines of Tumor Glycolysis and Transplantability , Proc Amer Ass Cancer Res 3:163, 1960. 20. John, H.A., and Bond, V.P.: Method of Labeling Tissues with Tritiated Thymidine in vitro and Its Use in Comparing Rates of Cell Proliferation in Duct Epithelium, Fibroadenoma and Carcinoma of Human Breast , Cancer 14:639-643, 1961.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png JAMA American Medical Association

Decreased Intoxication by Fluorouracil When Slowly Administered in Glucose

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References (21)

Publisher
American Medical Association
Copyright
Copyright © 1963 American Medical Association. All Rights Reserved.
ISSN
0098-7484
eISSN
1538-3598
DOI
10.1001/jama.1963.03060130030009
Publisher site
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Abstract

Abstract Moderate to severe systemic intoxication resulting from rapid intravenous injection of 5-fluorouracil in cancer chemotherapy has been reduced from an incidence of 50% to 60% to 6% in a series of 83 patients by use of infusions in 5% glucose over 8 hours. Doses of 10 to 25 gm per patient per course have been tolerated with minimal toxic reactions. There was objective palliation of metastases in 27% from drug therapy alone, and in a further 10% by treatment combined with hormonal or x-ray therapy. Avoidance of intoxication by slow intravenous infusion has broadened the opportunities for use of this drug in ambulatory therapy of colorectal, biliary tract, ovarian, and mammary cancer. References 1. Hoffman LaRoche, Inc, Nutley, N. J., Department of Clinical Investigation: Clinical Data Sheet 5-Fluorouracil (RO 2-9757). 2. Lemon, H.M.: Reduction of 5-Fluorouracil Toxicity in Man with Retention of Anticancer Effects, by Prolonged Intravenous Administration in 5% Dextrose , Cancer Chemother Rep 8:97-101 ( (July) ) 1960. 3. Sullivan, R.P., et al: Clinical Effects of Fluorinated Pyrimidines ( 5-Fluorouracil and 5 F Fluoro 2 1 deoxyuridine) , Cancer Chemother Rep 8:77-83 ( (July) ) 1960. 4. Wolberg, W.H., and Curreri, A.R.: Toxicity Studies of 5-Fluorouracil Used as Adjunct to Surgery , Arch Surg (Chicago) 81:244-250, 1960.Crossref 5. Krant, M.J.: Alterations in Administration of Fluorouracil; Experiences with Two-Hour Infusions , Cancer Chemother Rep 15:35-40, 1961. 6. Staley, C.J., et al: Various Methods of Administering 5-Fluorouracil , Cancer Chemother Rep 20:107-112, 1962. 7. Reitemeyer, R.J., and Moertel, C.G.: Comparison of Rapid and Slow Intravenous Methods of Administration of 5-Fluorouracil in Treatment of 100 Patients with Advanced Carcinoma of Large Intestine , Proc Amer Ass Cancer Res 3:353, 1962. 8. Frank, W.; Brennan, J.T.; Lo Presti, J.M.: Preliminary Pharmacologic Observations on Concomitant Use of X-ray and 5-Fluorouracil in Human Malignancies , Cancer Chemother Rep 11:145-146, 1961. 9. Ansfield, F.J., and Currieri, A.R.: Further Clinical Studies with 5-Fluorouracil , J Nat Cancer Inst 22:497-507, 1959. 10. Cornell, G.N., et al: Clinical Experience with 5-Fluorouracil in Treatment of Malignant Disease , Cancer Chemother Rep 9:23-30, 1960. 11. Olson, J.B., and Green, J.R.: Evaluation of 5-Fluorouracil in Treatment of Cancer , J Nat Cancer Inst 25:133-140, 1960. 12. Wilson, W.L.: Chemotherapy of Human Solid Tumors with 5-Fluorouracil , Cancer 13:1230-1239, 1960.Crossref 13. Vaitkevicius, V.K., et al: Clinical Evaluation of Cancer Chemotherapy with 5-Fluorouracil , Cancer 14:131, 1961.Crossref 14. Young, C.W., et al: Clinical Evaluation of 5-Fluorouracil and 5-Fluoro-2-Deoxyuridine in Solid Tumors in Adults, Progress Report , Cancer Chemother Rep 6:17-20 ( (Feb) ) 1960. 15. Gold, G.L., et al: Clinical Study of 5-Fluorouracil , Cancer Res 19:935-939, 1959. 16. Kahler, H., and Van Robertson, W.B.: Hydrogen Ion Concentration of Normal Liver and Hepatic Tumors , J Nat Cancer Inst 3:493, 1947. 17. Ross, W.J.C.: Increased Sensitivity of Walker Tumor Towards Aromatic Nitrogen Mustards Carrying Basic Side Chains Following Glucose Pre-Treatment , Biochem Pharmacol 8:235, 1961.Crossref 18. Heidelberger, C., et al: Studies on Fluorinated Pyrimidines X in vivo Studies on Tumor Resistance , Cancer Res 20:897-902, 1960. 19. Woods, N.W.; Hunter, J.C.; and Burls, D.: Glucose Enhancement of Inhibition by Fluorinated and Normal Pyrimidines of Tumor Glycolysis and Transplantability , Proc Amer Ass Cancer Res 3:163, 1960. 20. John, H.A., and Bond, V.P.: Method of Labeling Tissues with Tritiated Thymidine in vitro and Its Use in Comparing Rates of Cell Proliferation in Duct Epithelium, Fibroadenoma and Carcinoma of Human Breast , Cancer 14:639-643, 1961.Crossref

Journal

JAMA – American Medical Association

Published: Sep 28, 1963

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