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Therapy for advanced colorectal cancer

¹Clinical Investigation Program, Robert H. Lurie Cancer Center, Northwestern University, Chicago, IL 60611-2096, USA.

Seminars in Oncology

|October 24, 1998

Summary

Despite 45 years of use, 5-fluorouracil (5-FU) shows modest effectiveness for advanced colorectal cancer. Combinations and delivery methods like hepatic arterial infusion (HAI) improve response rates but not consistently survival outcomes.

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Area of Science:

Oncology
Medical Chemistry

Background:

5-fluorouracil (5-FU) is a long-standing treatment for advanced colorectal cancer with limited efficacy.
Enhancement strategies include biochemical modulators, altered dosage, and novel administration routes.

Purpose of the Study:

To evaluate the efficacy of 5-FU in combination with leucovorin.
To compare different 5-FU administration methods (bolus vs. infusion).
To assess the impact of hepatic arterial infusion (HAI) for liver-dominant colorectal cancer.

Main Methods:

Meta-analysis of 5-FU plus leucovorin versus 5-FU alone.
Comparison of 5-FU bolus injection versus prolonged infusion.
Clinical trials of HAI for liver metastases.

Main Results:

5-FU plus leucovorin significantly increased response rates but not survival.
Prolonged 5-FU infusion improved response rates and reduced toxicity, but survival benefits were not consistently significant.
HAI increased response rates compared to systemic fluoropyrimidines; one trial showed both response and survival benefits with HAI versus palliative care, without impacting quality of life.

Conclusions:

Current 5-FU based therapies remain standard first-line treatment for advanced colorectal cancer.
Ongoing trials are investigating 5-FU pro-drugs, oral combinations, thymidylate synthase inhibitors, and new combination regimens.
While response rates are often improved, significant survival benefits with modified 5-FU strategies require further validation.

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