Abstract
Two trials of CF-FUra in patients with metastatic colorectal cancer were performed, both using a 3 day loading dose and then weekly maintenance doses to minimize toxicity. The first trial used CF by IV infusion with constant dose of FUra 400 mg/m2, and the second trial used oral CF with escalating doses of FUra.
In the first trial, 45 eligible patients (20 with and 25 without prior therapy) were treated. Toxicity usually consisted of diarrhea or weakness and was controlled by delaying or decreasing 5FU dose. Subjective responses occurred in 75% of patients but did not correlate with antineoplastic effect. objective responses were seen in 36% and stabilization of disease in 31% of patients, and correlated with prolonged survival. Median survival was 8 months for patients with prior treatment and 10 for those without, and 12 month survival was 32% and 40%, respectively. There was no correlation between the development of toxicity and response or survival.
The second trial was recently conducted in cooperation with Duke University to determine toxicity and efficacy of oral CF with IV FUra prior to a randomized trial of this combination versus placebo with IV FUra. Eighteen patients were treated and serum levels of folates were obtained on 10. First toxicity occurred at FUra doses ranging from 375 to 850 mg/m2, and consisted of diarrhea in 9, lethargy in 7, nausea/ vomiting in 4, dermatitis in 4, conjunctivitis in 2, hypersalivation in 2, stomatitis in 1, and profound granulocytopenia in 1. Response rate was 35% and stabilization was 35% with median survival of 14 months and 12 month survival of 56%.
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References
S. G. Arbuck, 5-FU/Leucovorin: Biochemical modulation that works?, Oncology 1: 61 (1987).
T. R. Buroker, C. G. Moertel, T. R. Fleming, et al., A controlled evaluation of recent approaches to biochemical modulation or enhancement of 5-fluorouracil therapy in colorectal carcinoma, J. Clin. Oncol. 3: 1624 (1985).
S. K. Carter, Large bowel cancer: The current status of treatment, JNCI 56: 3 (1976).
D. Machover, G. Schwarzenberg, E. Goldschmidt, et al., Treatment of advanced colorectal and gastric adenocarcinomas with 5FU combined with high dose folinic acid: A pilot study, Cancer Treat. Rep. 66: 1803 (1982).
H. W. Bruckner, T. Ohnuma, R. Hart, et al., Leucovorin (LV) potentiation of 5-fluorouracil (FU) efficiency and potency, Proc. Am. Assoc. Cancer Res. 23: 111 (1982).
L. R. Laufman, K. A. Krzeczowski, R. Roach, et al., Leucovorin-5fluorouracil: An effective treatment for metastatic colon cancer, J. Clin. Oncol. 5: 1394 (1987).
N. Petrelli, L. Herrera, Y. Rustum, et al., A prospective randomized trial of 5-fluorouracil versus 5-flurouracil and high-dose leucovorin versus 5-fluorouracil and methotrexate in previously untreated patients with advanced colorectal carcinoma, J. Clin. Oncol. 5: 1559 (1987).
C. Erlichman, S. Fine, A. Wong, et al., A randomized trial of fluorouracil and folinic acid in patients with metastatic colorectal carcinoma, J. Clin. Oncol. 6: 469 (1988).
M. J. O’Connell and H. S. Wieand, A controlled clinical trial including folinic acid at two distinct dose levels in combination with 5-fluorouracil (5FU) for the treatment of advanced colorectal cancer: Experience of the Mayo Clinic and North Central Cancer Treatment Group, This Volume.
B. W. McGuire, L. L. Sia, J. D. Hayes, et al., Absorption kinetics of orally administered leucovorin calcium: Development of folates and folic acid antagonists in cancer chemotherapy, NCI Monograph 5: 47 (1987).
J. A. Straw, D. Szapary and W. T. Wynn, Pharmacokinetics of the diastereoisomers of leucovorin after intravenous and oral administration to normal subjects, Cancer Pes. 44: 3114 (1984).
J. D. Hines, D. J. Adelstein, J. Bast, et al., High-dose oral (PO) leucovorin (CF) and intravenous 5-fluorouracil (5FU) in advanced metastatic colorectal carcinoma: Results of a pilot-phase I study, Proc. Am. Soc. Clin. Oncol. 7: 110 (1988).
E. M. Newman and J. F. Tsai, Microbiological analysis of 5 formyl THE and other folates using an automatic 96 well plate reader, Analyt. Biochem. 154: 509 (1986).
D. S. Duch, S. W. Bowers and C. A. Nichol, Analysis of cofactor levels in tissues using high performance liquid chromatography, Anal. Biochem. 130: 385 (1983).
R. J. Mullin, B. R. Kieth and D. S. Duch, Distribution and metabolism of calcium leucovorin in normal and tumor tissue, This Volume.
E. E. Vokes, K E. Choi, R. L. Schilsky, et al, Cisplatin, fluorouracil, and high-dose leucovorin for recurrent or metastatic head and neck cancer, J. Clin. Oncol. 6: 618 (1988).
K. E. Choi and R. L. Schilsky, Resolution of the stereosiomers of LV and 5MTHF by chiral high performance liquid chromatography, Analytical Biochem. 168: 398 (1988).
R. M. Evans, J. D. Laskin and M. T. Hakala, Effects of excess folates and deoxyinosine on the activity and site of action of 5-fluorouracil, Cancer Res. 41: 3288 (1981).
B. Ullman, M. Lee, D. W. Martin Jr., et al., Cytotoxicity of 5-fluoro-2’-deoxyuridine: Requirement for reduced folate cofactors and antagonism by methotrexate, Proc. Natl. Acad. Sci. USA 75: 980 (1978).
K. Keyomarsi and R. G. Moran, Folinic acid augmentation of the effects of fluoropyrimidines on murine and human leukemic cells, Cancer Res. 46: 5229 (1986).
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© 1988 Plenum Press, New York
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Laufman, L.R. et al. (1988). Clinical Experience with CF-FUra. In: Rustum, Y., McGuire, J.J. (eds) The Expanding Role of Folates and Fluoropyrimidines in Cancer Chemotherapy. Advances in Experimental Medicine and Biology, vol 244. Springer, New York, NY. https://doi.org/10.1007/978-1-4684-5607-3_21
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DOI: https://doi.org/10.1007/978-1-4684-5607-3_21
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