Summary
The limiting toxicity of low dose continuous infusion 5-fluorouracil (200–300 mg/m2/day) is often palmarplantar erythrodysesthesia (PPE). PPE developed in 16/25 patients (exact 95% confidence interval of 42% –82%) with metastatic colon cancer enrolled in a phase II trial. In this trial, 5-FU was given continuously at a dose of 200 mg/m2/day until toxicity or progressive disease forced discontinuation.
The first signs of the syndrome developed at a median of 2 months following infusion initiation and, unless treatment was interrupted, became progressively worse. The incidence of moderate to severe PPE was 71% in the 14 previously untreated patients (exact 95% confidence intervals of 42–92%). Seventy-eight percent of the responders in the no prior treatment group developed PPE. The incidence of moderate to severe PPE was only 27% in the 11 previously treated patients (exact 95% confidence intervals of 6–61%). The higher incidence of PPE in the previously untreated patients probably resulted from a longer total infusion time (median = 7.3 months) than the previously treated (median = 4.5 months). The longer infusion time in turn was a result of the higher response rates (64 vs 18%) in the previously untreated versus treated groups.
Five previously untreated patients who developed PPE received 50 or 150 mg of pyridoxine/day when moderate PPE changes were noted. Reversal of PPE without interruption of the 5-FU was seen in 4/5 patients. Four of these patients who received pyridoxine had responded to 5-FU treatment. No adverse affect of pyridoxine on clinical response was noted.
The five previously untreated patients who received pyridoxine for PPE continued 5-FU for a median of 6 months after development of the syndrome. The six previously untreated patients who did not receive pyridoxine when they developed PPE were able to continue 5-FU for a median of only 2.5 months after development of the syndrome. A similar number of clinical responders to 5-FU were present in both groups.
Considering the high incidence of PPE and response in previously untreated colon cancer patients who receive protracted continuous 5-FU, prophylactic pyridoxine in conjunction with this treatment modality might be useful.
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References
Benedetto P, Bogos M, Morillo G, Sfakianakias G: Chronic continuous infusion of 5-Fluorouracil in previously untreat ed patients with measurable metastatic colorectal cancer. (Abstr) Proc Amer Soc Clin Oncol 5:92, 1986
Faintuch JS, Sheppard KV, Gaynor E, O'Laughlin K, Bechorner J, Levin B: Continuous Infusion 5-FU: A dose escalating schedule. (Abstr) Proc Amer Soc Clin Oncol 5:93, 1986
Faintuch JS, Sheppard KV, O'Laughlin K, Bechorner J, Gaynor E, Levin B: Toxicity of continuous infusion 5-FU. (Abstr) Proc Amer Soc Clin Oncol 4:92, 1985
Wade JL, Herbst S, Greenberg A: Prolonged venous infusion (PVI) of 5-Fluorouracil (5-FU) for metastatic colon canceer. (Abstr) Proc Amer Soc Clin Oncol 5:88, 1986
Belt RJ, Davidner ML, Myron MC, Barrett S: Continuous low dose 5-Fluorouracil for adenocarcinoma: Conformation of activity. (Abstr) Proc Amer Soc Clin Oncol 5:90, 1986
Caballero GA, Ausman RK, Quellman EJ: Long term, ambulatory, continuous IV infusion of 5-FU for the treatment of advanced adenocarcinoma. Cancer Treat Rep 69:13–15, 1985
Lokich J, Ahlgren J, Gullo J, Phillips J, Fryer J: A randomized trial of standard bolus 5-FU vs. protracted infusional 5-FU in advanced colon cancer. (Abstr) Proc Amer Soc Clin Oncol 5:81, 1987
Lokich JJ, Moore C: Chemotherapy-associated palmar plantar erythrodysesthesia syndrome. Ann Intern Med 101:798–800, 1984
Leichman L, Leichman CG, Kinzie J, Weaver D, Evans L: Long term low dose 5-Fluorouracil in advanced measurable colon cancer: No correlation between toxicity and efficacy. (Abstr) Proc Amer Soc Clin Oncol 4:86, 1985
Hansen R, Ausman R, Ritch P, Anderson T, Schulte W, Frick J: Continuous 5-Fluorouracil (5-FU) infusion in colorectal cancer: Update of the MCW experience. (Abstr) Proc Amer Soc Clin Oncol 6:80, 1987
Lockich J, Fine N, Perri J, Bothe A: Protracted ambulatory venous infusion of 5-Fluorouracil. Am J Clin Oncol 1:103–107, 1983
Gyorgy P, Eckardt R: Vitamin B6 and skin lesions in rats. Nature 144:512, 1939
Slavik M, Smith KS, Blanc O: Decrease of serum pyridoxal phosphate levels and homocystinema after administration of 6-azauridine triacetate and their prevention by administration of pyridoxine. Biochem Pharmac 31:4089–4092, 1982
Slavik M, Blanc O, Smith K, Slavik J: 6-Azauridine triacetate induced hyper-B-alaninemia and its decrease by administration of pyridoxine. J Nutr Sci Vitaminol 29:631–635, 1983
Kubo K, Fanatsuka A, Tamaki N: The in vivo decrease of B-alanine-5-oxoglutarate aminotransferase activity caused by 6-Azauracil and 5-Fluorouracil. J Nutr Sci Vitaminol 28:575–578, 1982
Diem K, Lenter G, Eds: Scientific Tables. 7th ed., Ardsley, New York, Ciba-Giegy Corp, 85–86, 1970
Baker LH, Talley RW, Matter R, Lehane DE, Ruffmer BW, Jones SE, Morrison FS, Stephens RL, Gehan EA, Vaitkevicius VK: Phase III comparison of the treatment of advanced gastrointestinal cancer with bolus weekly 5-FU vs. Methyl-CCNU plus weekly 5-FU: A Southwest Oncology Group Study. Cancer 38:1–7, 1976
Ansfield FJ: A less toxic fluorouracil dosage schedule. JAMA 190:686–688, 1964
Ansfield FJ, Klotz J, Nealon T, Ramirez G, Minton J, Hill G, Wilson W, Davis H, Cornell G: A phase III study comparing the clinical utility of four regimens of 5-Fluorouracil: A preliminary report. Cancer 39:34–40, 1977
Calabro-Jones PM, Byfield JE, Ward JF, Sharp TR: Time dose relationship for 5-Fluorouracil cytotoxicity against human epithelial cancer cells in vitro. Cancer Res 42:4413–4420, 1982
Drewinko B, Yang L: Cellular basis for the inefficacy of 5-FU in human colon carcinoma. Cancer Treat Rep 69:1391–1398, 1985
Seifert P, Baker LH, Reed ML, Vaitkevicius VK: Comparison of continuously infused 5-Fluorouracil with bolus injection in treatment of patients with colorectal adenocarcinoma. Cancer 36:123–128, 1978
Budd GT, Fleming GR, Bukowski RM, McCracken JD, Rivkin SE, O'Bryan RM, Balcerzak SP, McDonald JS: 5-Fluorouracil and folinic acid in the treatment of metastatic colorectal cancer: A randomized comparison: A Southwest Oncology Group Study. J Clin Oncol 5:272–277, 1987
Machover D, Goldschmidt E, Chollet P, Metzger G, Zitton J, Marquet J, Vanderbulcke JM, Misset JL, Schwarzenberg L, Fourtillan JB, Gaget H, Mathe G: Treatment of advanced colorectal and gastric adenocarcinomas with 5-Fluorouracil and high-dose folinic acid. J Clin Oncol 4:685–696, 1986
Valone FH, Drakes T, Flam M, Hannigan J: Randomized trial of 5-FU vs Leucovorin (LV) plus 5-FU vs sequential methotrexate (MTX), 5-FU Leucovorin in patients with advanced colorectal carcinoma: A Northern California Oncology Group Trial. (Abstr) Proc Amer Soc Clin Oncol 7:95, 1988
Petrelli N, Herrera L, Rustrum Y, Burke P, Creaven P, Stole J, Emrich LJ, Mittelman A: A prospective randomized trial of 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
Stagand JJ, Bergerat JP, White RA, Hokanson J, Drewinko B: Biological and cell kinetic properties of a human colonic adenocarcinoma (Lovo) grown in athymic mice. Cancer Res 40:2846–2852, 1980
Sharp TR, Frankel SS, Byfield JE, Callipari F, Hornbeck CL: Combined infusional 5-FU and x-ray therapy (XRT) for advanced head and neck cancer-scheduling of radiosensitization programs. (Abstr) Proc Amer Soc Clin Oncol 2:168, 1983
Holyoke ED, Chu TM, Murphy GP: CEA as a monitor of gastrointestinal malignancy. Cancer 35:830–836, 1975
Mach JP, Jaeger PH, Bertholet MM, Ruegsegger CA, Loosli RM, Pettavel J: Detection of recurrence of large bowel carcinoma by radio-immunoassay of circulating carcinoembryonic antigen (CEA). Lancet 2:535–540, 1974
Mackay AM, Patel S, Carter S, Stevens U, Laurence DJ, Cooper EH, Neville AM: Role of serial plasma CEA assays in detection of recurrent and metastatic colorectal carcinomas. Br Med J 4:382–385, 1974
Sugerbaker PH, Zamcheck N, Moore FD: Assessment of serial carcinoembryonic antigen (CEA) assays in postoperative detection of recurrent colorectal cancer. Cancer 38:2310–2315, 1976
Ravry M, Moertel CG, Schutt AJ, Go VLW: Usefulness of serial serum carcinoembryonic antigen (CEA) determinations during anti-cancer therapy or long term follow-up of gastrointestinal carcinoma. Cancer 34:1230–1234, 1974
Mayer RJ, Garnick MB, Steele GD, Zamcheck N: Carcinoembryonic Antigen (CEA) as a monitor of chemotherapy in desseminated colorectal cancer. Cancer 42:1428–1433, 1978
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Fabian, C.J., Molina, R., Slavik, M. et al. Pyridoxine therapy for palmar-plantar erythrodysesthesia associated with continuous 5-fluorouracil infusion. Invest New Drugs 8, 57–63 (1990). https://doi.org/10.1007/BF00216925
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DOI: https://doi.org/10.1007/BF00216925