Journal of Clinical Oncology, Vol 15, 2432-2441, Copyright © 1997 by American Society of Clinical Oncology
Adjuvant chemotherapy in colorectal cancer with high-dose leucovorin and fluorouracil: impact on disease-free survival and overall survival
A Zaniboni
Illa Medicina Fondazione Beretta, Servizio di Oncologia, Spedali Civili, Brescia, Italy.
PURPOSE: The rationale for using adjuvant chemotherapy in colorectal cancer
is to achieve better disease control and thus reduce the high rates of
tumor recurrence and mortality in patients who undergo curative surgery.
The current literature, including relevant abstracts, on clinical trials of
fluorouracil (5-FU) in combination with high-dose leucovorin as adjuvant
chemotherapy for colorectal cancer is reviewed. The intent is not to
present new data, but to present the reader with a broad perspective and
larger patient experience on which to base well- reasoned treatment
decisions. DESIGN: Published clinical trials and abstracts presented at the
1996 American Society of Clinical Oncology (ASCO) meeting that assessed
5-FU in combination with high-dose leucovorin as adjuvant chemotherapy for
colorectal cancer were surveyed. End points of interest were disease-free
survival (DFS), overall survival, and toxicity. RESULTS: In randomized
trials that used high-dose leucovorin at doses that ranged from
daily-times-five 200 mg/m2 to weekly 500 mg/m2 in combination with 5-FU,
significant improvements in both DFS and overall survival were observed
over surgery alone (control). In patients treated with high-dose
leucovorin/5-FU, DFS rates ranged from 71% to 77% compared with control
(58% to 64%). A similar trend was seen in overall survival, with a range of
75% to 84% compared with control (63% to 77%). Toxicities observed for
high-dose leucovorin administered on a weekly or daily- times-five schedule
were diarrhea, stomatitis, myelosuppression, and nausea. CONCLUSION:
Overall, the results of these randomized trials support the use of
high-dose leucovorin/5-FU as adjuvant therapy for colorectal cancer. Longer
follow-up studies are needed to compare the benefits of these different
regimens in terms of survival and to characterize adverse effects,
especially those that may not be immediately evident. Adjuvant therapy with
high-dose leucovorin/5-FU is an effective regimen that is well tolerated by
many patients with colorectal cancer.
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