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Progress in Colorectal Cancer Chemotherapy

How Far Have We Come, How Far to Go?

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Abstract

Fluorouracil has been the mainstay of treatment for colorectal cancer (CRC) for almost 40 years. Various schedules and biochemical modulators have been investigated in an attempt to improve the therapeutic efficacy of fluorouracil. To date, fluorouracil plus folinic acid represents the standard therapy in CRC for the adjuvant treatment of patients at high risk for relapse and for the first-line treatment of metastatic disease.

Combination chemotherapy regimens have not been developed due to the lack of other active agents. However, the availability of several novel agents now allows investigation of combination regimens in this disease. One group of such agents, the oral fluoropyrimidines (tegafur/uracil plus oral folinic acid, capecitabine, eniluracil plus oral fluorouracil, and tegafur/gimeracil/potassium oxonate), are convenient oral alternatives to intravenous fluorouracil. A particular advantage of these oral agents is the reduction in the incidence of febrile neutropenia and mucositis compared with fluorouracil given in an intravenous bolus schedule. To gain clinical acceptance, however, oral fluoropyrimidines must confer at least the same survival advantages associated with the optimal intravenous fluorouracil regimens.

Irinotecan and oxaliplatin are 2 other novel agents that have mechanisms of action that are uniquely different from those of fluorouracil, with demonstrated activity in patients with fluorouracil-refractory disease. Recent randomised trials comparing fluorouracil plus folinic acid with combinations of either irinotecan or oxaliplatin and fluorouracil plus folinic acid have shown that response rates are improved and time to progression is increased in patients receiving the combination regimens. These regimens are being rapidly introduced in the adjuvant setting, and the role and acceptance of these combination regimens as first-line therapy needs to be defined.

Other novel agents being evaluated in the treatment of patients with advanced CRC include oral edrecolomab (monoclonal antibody 17-1A) and tumour vaccines.

Future research is focused on enabling clinicians to individualise treatment strategies in patients with CRC, so as to improve clinical outcomes and reduce drug toxicity.

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Authors and Affiliations

  1. Division of Medicine, University of Texas, M. D. Anderson Cancer Center, Houston, Texas, USA

    Melanie E. Royce

  2. Department of GI Oncology and Digestive Diseases, University of Texas M. D. Anderson Cancer Center, Box 78, 1515 Holcombe Boulevard, Houston, Texas, 77030, USA

    Paulo M. Hoff

  3. Division of Oncology Products, Center for Drug Evaluation and Treatment, Food and Drug Administration, Rockville, Maryland, USA

    Richard Pazdur

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Correspondence to Paulo M. Hoff.

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The views expressed are the results of independent work and do not represent the views or findings of the United States Food and Drug Administration.

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Royce, M.E., Hoff, P.M. & Pazdur, R. Progress in Colorectal Cancer Chemotherapy. Drugs & Aging 17, 201–216 (2000). https://doi.org/10.2165/00002512-200017030-00004

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