Abstract
Six patients with incurable malignancies wereoriginally treated with vitamin E, 3200 IU/day for fourteendays, followed by the same dose of vitamin E daily plus LCV(20 mg/m2 iv bolus daily × 5) with 5FU (425mg/m2 iv bolus immediately following LCV). The sameschedule of LCV and 5FU was repeated 4 weeks later, then every5 weeks indefinitely. When 3 of the first 6 had grade 3/4toxicity, six more patients were treated on the identicaldrugs and schedule. Seven of twelve total patients had one ormore grade 3/4 toxicities. Neutropenia, abdominal pain, anddiarrhea were most common. No patient had a documentedresponse, though seven patients did have stable disease.Though the combination of vitamin E and chemotherapy wastoxic, this trial demonstrated maximal therapeutic doses ofvitamin E can be combined with standard 5FU and LCV, withoutsignificantly increasing the side effects of thechemotherapy itself.
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Petrelli N, Herrera L, Rustum Y, Burke P, Creaven P, Stulc J, Emrich U, Mittelman A: A prospective randomized trial of 5–fluorouracil versus 5–fluorouracil and high-dose leucovorin versus 5–fluorouracil and methotrexate in previously untreated patients with advanced colorectal carcinoma. J Clin Oncol 5: 1559–1565, 1987
Coombes RC, Chilvers CE, Amadori D, Medi F, Fountzilas G, Rauschecker H, Vassilopoulos P, Ferreira EP, Vannozzi G, Bliss JM: Randomized trial of epirubicin versus fluorouracil in advanced gastric cancer. An International Collaborative Cancer Group (ICCG) study. Ann Oncol 5: 33–36, 1994
Comis RL, Carter SK: A review of chemotherapy in gastric cancer. Cancer 34: 1576–1586, 1974
Poon MA, O'Connell MJ, Moertel CG, Wiend HS, Cullinan SA, Everson LK, Krook JE, Mailliard JA, Laurie JA, Tschetter LK: Biochemical modulation of fluorouracil: Evidence of significant improvement of survival and quality of life in patients with advanced colorectal carcinoma. J Clin Oncol 7: 1407–1417, 1989
Poon MA, O'Connell MJ, Wieand HS, Krook JE, Gerstner JB, Tschetter LK, Levitt R, Kardinal CG, Mailliard JA: Biochemical modulation of fluorouracil with leucovorin: Confirmatory evidence of improved therapeutic efficacy in advanced colorectal cancer. J Clin Oncol 9: 1967–1972, 1991
Stone WL, Papas AM: Tocopherols and the etiology of colon cancer. J Natl Cancer Inst 89: 1006–1014, 1997
Byers T, Perry G: Dietary carotene, vitamin C, and vitamin E as protective antioxidants in human cancers. Annu Rev Nutr 12: 139–159, 1992
Greenwald P, Kelloff GJ, Burch-Whitman C, Kramer BS: Chemoprevention. CA Cancer J Clin 45: 31–49, 1995
Turley JM, Funakoshi S, Ruscetti FW, Kasper J, Murphy WJ, Longo DL, Birchenall-Roberts MC: Growth inhibition and apoptosis of RL human B lymphoma cells by vitamin E succinate and retinoic acid: Role for transforming growth factor B. Cell Growth Differ 6: 655–663, 1995
Tsai JC, Jain M, Hsieh CM, Lee WS, Yoshizumi M, Patterson C, Perrella MA, Cooke C, Wang H, Haber F, Schlegal R, Lee ME: Induction of apoptosis by pyrrolidinedithiocarbarnate and N-acetylcysteine in vascular smoothmuscle cells. J Biol Chem 271: 3667–3670, 1996
Machlin LJ: Vitamin E. In: Machlin LJ (ed), Handbook of vitamins: Nutritional, biochemical, and clinical aspects. Marcell Dekker inc, New York, 1984, pp. 100–145
Anderson TW, Reid DBW: A double-blind trial of vitamin E in angina pectoris. Am J Clin Nutr 27: 1174–1178, 1974
Chinery R, Brockman JA, Peeler MO, Shyr Y, Beauchamp RD, Coffey RJ: Antioxidants enhance the cytotoxicity of chemotherapeutic agents in colorectal cancer: A p53–independent induction of p21WAF1=CIP1 via C/EBPβ. Nat Med 11: 1233–1241, 1997
Potrono C, FitzGerald GA: Isoprostanes: Potential markers of oxidant stress in atherothrombotic disease. Arterioscler Thromb & Vasc Biol 17: 2309–2315, 1997
Patrico D, Reilly M, Lawson JA, FitzGerald GA: Novel indices of oxidant stress in cardiovascular disease: Specific analysis of F2-isoprostanes. Agents Actions (Suppl) 48: 25–41, 1997
Morrow JD, Roberts LJ: Mass spectrometric quantification of F2–isoprostanes in biological fluids and tissues as a measure of oxidant stress. Meth Enzymol 300: 3–12, 1999
SAS Institute Inc., Cary, NC USA
Scheithauer W, Depisch D, Kornek G, Pidlich J, Rosen H, Karall M, Prochaska M, Ernst A, Sebesta C, Eckhardt S: Randomized comparison of fluorouracil and leucovorin therapy versus fluorouracil, leucovorin and cisplatin therapy in patients with advanced colorectal cancer. Cancer 73: 1562–1568, 1994
Meta-Analysis Group in Cancer: Efficacy of intravenous continuous infusion of fluorouracil compared with bolus administration in advanced colorectal cancer. J Clin Oncol 15: 301–308, 1998
Vincent M, Whiston F, Tomiak A: Mini-meta analysis of toxicity of full dose Mayo regimen (FUFA) from two randomized trials: A concern about dose. (abstr) Proc Am Soc Clin Oncol 18: 242A, 1999
de Gramont A, Bosset J-F, Milan C, Rougier P, Bouche O, Etienne P-L, Morvan F, Louvet C, Guillot T, Francois E, Bedenne L: Randomized trial comparing monthly low-dose leucovorin and fluorouracil bolus with bimonthly high-dose leucovorin and fluorouracil bolus plus continuous infusion for advanced colorectal cancer: A French Intergroup study. J Clin Oncol 15: 808–815, 1997
Leventhal BG, Wittes RE: Research methods in clinical oncology. Raven Press, New York, 1998
Saltz LB, Douillard J, Pirotta N, Asad L, Elfring GL, Gruia G, Locker PK, Alakl M, Knight RD, Miller LL: Combined analysis of two phase III randomized trials comparing irinotecan, fluorouracil, leucovorin versus fluorouracil alone as first-line therapy of previously untircated colorectal cancer. (abstr) Proc Am Soc Clin Oncol 19: 242a, 2000 Address for offprints: Charles D. Blanke, OHSU Oncology, MC OP28, 3181 S.W. Sam Jackson, Park Road, Portland OR 97232, USA
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Blanke, C.D., Stipanov, M., Morrow, J. et al. A Phase I Study of Vitamin E, 5-Fluorouracil and Leucovorin for Advanced Malignancies. Invest New Drugs 19, 21–27 (2001). https://doi.org/10.1023/A:1006484031959
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DOI: https://doi.org/10.1023/A:1006484031959