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Systemic therapy for colorectal cancer: an overview
1Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.
Seminars in Oncology
|October 1, 1991
Summary
Systemic 5-fluorouracil (5-FU) remains key for colorectal cancer. While parenteral 5-FU is better than oral for metastatic disease, new strategies aim to enhance its effectiveness, with promising adjuvant results for stage C colon cancer.
Area of Science:
- Oncology
- Medical Oncology
- Cancer Chemotherapy
Background:
- 5-fluorouracil (5-FU) is the cornerstone of systemic treatment for colorectal cancer.
- Parenteral 5-FU demonstrates superiority over oral administration in metastatic settings, though administration schedules do not significantly impact survival.
- Combination therapies with agents like semustine or mitomycin C have not shown added benefit.
Purpose of the Study:
- To evaluate novel strategies for enhancing 5-FU efficacy in colorectal cancer treatment.
- To compare different pharmacologic approaches aimed at increasing 5-FU's incorporation into RNA or DNA.
- To assess the efficacy of regional chemotherapy and adjuvant therapies.
Main Methods:
- Investigating 5-FU enhancement via methotrexate or PALA for RNA incorporation.
- Examining folinic acid for enhanced DNA synthesis inhibition.
- Evaluating alpha-interferon's modulatory effects.
- Analyzing results from randomized trials on intra-arterial hepatic infusions.
- Reviewing adjuvant chemotherapy trials for colon and rectal cancer.
Main Results:
- Regional chemotherapy via hepatic infusion improved hepatic response rates but not survival, with notable toxicity.
- Adjuvant chemotherapy (5-FU + levamisole) in stage C colon cancer reduced recurrence and prolonged survival.
- Combined radiation and chemotherapy showed benefits in stages B2 and C rectal cancer.
Conclusions:
- Ongoing trials are comparing pharmacologic strategies to boost 5-FU activity.
- Regional chemotherapy offers local benefits but limited survival advantages in colorectal cancer.
- Adjuvant 5-FU plus levamisole and combined modality treatments represent significant advances in managing earlier-stage colorectal and rectal cancers.