Effective biomodulation by leucovorin of high-dose infusion fluorouracil given as a weekly 24-hour infusion: results of a randomized trial in patients with advanced colorectal cancer

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Item Type:	Article
Title:	Effective biomodulation by leucovorin of high-dose infusion fluorouracil given as a weekly 24-hour infusion: results of a randomized trial in patients with advanced colorectal cancer
Creators Name:	Koehne, C.H., Schoeffski, P., Wilke, H., Kaeufer, C., Andreesen, R., Ohl, U., Klaasen, U., Westerhausen, M., Hiddemann, W., Schott, G., Harstick, A., Bade, J., Horster, A., Schubert, U., Hecker, H., Doerken, B. and Schmoll, H.J.
Abstract:	PURPOSE: To determine whether high-dose infusional fluorouracil (FU) is effectively modulated by leucovorin (LV), interferon (IFN) alpha-2b, or both when given to patients with metastatic colorectal cancer. PATIENTS AND METHODS: Patients (n = 236) with progressive, measurable disease were randomized to three groups and received FU 2,600 mg/m2 as a 24-hour continuous infusion (CI) weekly for 6 weeks with 2 weeks rest (FU24h) and LV 500 mg/m2 as a 2-hour infusion before FU or IFN 3 x 10(6) U subcutaneously 3 times weekly or both. Treatment continued until progressive disease or unacceptable toxicity was observed. Pairs of treatment arms were analyzed sequentially to detect equivalence or a 25% difference in response rates. RESULTS: The rate of objective remission in patients who received FU24h/LV (44%; 40 of 91) was significantly higher than in patients who received FU24h/IFN (18%; 16 of 90; P < .05). The response rates of patients who received FU24h/LV versus FU24h/LV/IFN (27%; 13 of 49) were statistically equivalent. Significant differences were observed for time to tumor progression (TTP) (FU24h/LV, 7.1 months; FU24h/IFN, 3.9 months; FU24h/LV/IFN, 6.3 months; global P value < .009) and survival (16.6 months, 12.7 months, 19.6 months, respectively; global P value < .04). Unpredictable and life-threatening toxicity in the FU24h/LV/IFN arm required dose reduction of FU to 2,000 mg/m2/day and early stoppage of this arm. Toxicity was manageable in patients who received both FU24h/LV (grade 3 to 4 diarrhea, 21%) and FU24h/IFN (grade 3 to 4 diarrhea, 15%). CONCLUSION: Response rate, TTP, and overall survival were superior for LV-containing regimens compared with IFN modulation alone. The addition of IFN to high-dose infusional FU plus LV offers no advantage and may increase toxicity. The regimen of high-dose infusional FU24h/LV warrants further evaluation in patients with metastatic colorectal cancer.
Keywords:	Antineoplastic Antimetabolites, Colorectal Neoplasms, Disease Progression, Drug Administration Schedule, Fluorouracil, Immunologic Factors, Intravenous Infusions, Interferon Alfa-2b, Leucovorin, Prospective Studies, Survival Rate
Source:	Journal of Clinical Oncology
ISSN:	0732-183X
Publisher:	American Society of Clinical Oncology
Volume:	16
Number:	2
Page Range:	418-426
Date:	February 1998
Official Publication:	https://doi.org/10.1200/JCO.1998.16.2.418
PubMed:	View item in PubMed

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