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Overview of clinical trials using 5‐fluorouracil and leucovorin for the treatment of colorectal cancer
Author(s) -
Arbuck Susan G.
Publication year - 1989
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(19890315)63:6+<1036::aid-cncr2820631309>3.0.co;2-k
Subject(s) - medicine , fluorouracil , toxicity , colorectal cancer , gastroenterology , surgery , chemotherapy , cancer
Results from five completed and two ongoing Phase III trials comparing 5‐fluorouracil (5‐FU) with 5‐FU and leucovorin (LV) for the treatment of advanced, previously untreated colorectal carcinoma are reviewed. In five of these studies, 5‐FU/LV was shown to provide a significantly higher response rate than 5‐FU alone. Partial response rates resulting from the combination ranged from 16% to 45%, while those obtained with 5‐FU alone were 5% to 18%. Complete responses with either treatment occurred in 0% to 8% of the patients treated. In two of the studies, 5‐FU treatment prolonged median survival by 3 and 6 months. The planned dose intensities (DI) for single‐agent 5‐FU ranged from 463 to 760 mg/m 2 /week, and the actual delivered DI, established in two of the trials, were 531 and 533 mg/m 2 /week. The planned 5‐FU DI for the 5‐FU/LV combination ranged from 463 to 600 mg/m 2 /week compared with the delivered DI of 461 and 463 mg/m 2 /week. When used with LV, 5‐FU cannot be administered at the single‐agent maximum tolerated dose because of unacceptable toxicity. Nevertheless, lower doses of 5‐FU, when combined with LV, had higher response rates than 5‐FU alone. Significant toxicity occurred with 5‐FU and with the combination. The addition of LV to 5‐FU changed the type of toxicity that resulted; that toxicity varied with the schedule followed. The real, but modest improvement that resulted from the combination of 5‐FU with the metabolic modulator LV offers the possibility that the administration of 5‐FU/LV in the adjuvant setting will prolong survival and increase the percentage of patients cured of their disease. Furthermore, other compounds that modulate the effects of 5‐FU may be capable of providing additional therapeutic benefits.