Adjuvant treatment of colorectal cancer
Section snippets
Colon cancer
Based on the activity of 5-fluorouracil (5-FU) in advanced colorectal cancer, several trials, both randomized and non-randomized, have compared CT with observation alone after radical surgical resection. These trials were insufficiently large to detect differences in survival between two arms and only a small benefit for CT was hypothesized. In 1988 the results of these trials were subjected to meta-analysis: 5-FU treatment was found to have decreased the risk of death (hazard ratio 0.83; 95%
The facts
Table 1 shows the principal randomized trials in adjuvant therapy. Evolution in adjuvant therapy can be simplified thus:
- •
In 1990 it was first demonstrated that 5-FU/levamisole is better than observation alone,
- •
In 1994 5-FU/leucovorin was also found better than observation alone,
- •
In 1998 5-FU/leucovorin was found better than 5-FU+levamisole, and the addition of levamisole to 5-FU/leucovorin was shown to be unnecessary,
- •
6 months of adjuvant CT have obtained the same results as 12 months,
- •
High-dose and
“To B or not to B?”
In contrast to Dukes C colon cancer, there is as yet no convincing evidence of benefit from adjuvant CT for Dukes B colon cancer. Overall, patients with stage II colon cancer have a 75–85% 5-year survival after surgical resection [39].
Data from patients in Dukes stage B from the NSABP studies were pooled, based on similar eligibility criteria. In the C-01→C-04 trials there were 1565 patients with Dukes B disease [60]. This was not a meta-analysis but rather a relative estimation of the benefits
The new data (almost mature and preliminary)
Table 2 itemises the most recent trials; we suggest the following:
- •
Outside of clinical trials, adjuvant therapy should be widely used in Dukes stage B colon cancer. Physicians must evaluate the individual patient's level of risk. Weekly low-dose 5-FU/leucovorin could be the best option in this setting.
- •
Elderly patients should be treated as younger patients if they have no important comorbidities or frailty.
- •
Infusional 5-FU can be used in adjuvancy; one should expect the same activity as with a
The conclusion
Adjuvant therapy should be always considered in patients with radically resected colon cancer. 5-FU-based schedules remain the standard treatment in this setting; combination therapy can be considered in patients at high risk. Interesting studies on target-oriented therapy are in progress.
New ways to detect patients at high risk are necessary to improve future results, such as molecular markers, genetic patterning and pharmacogenomics.
In rectal cancer, combined chemoradiotherapy should be
References (78)
- et al.
5-Fluorouracil plus leucovorin is an effective adjuvant chemotherapy in curatively resected stage III colon cancerlong-term follow-up results of the adjCCA-01 trial
Annals of Oncology
(2003) - et al.
Edrecolomab alone or in combination with fluorouracil and folinic acid in the adjuvant treatment of stage III colon cancera randomised study
Lancet
(2002) - et al.
T3N0 rectal cancerresults following sharp mesorectal excision and no adjuvant therapy
Journal of Gastrointestinal Surgery
(1999) - et al.
Preoperative infusional chemoradiation therapy for stage T3 rectal cancer
International Journal of Radiation Oncology, Biology, Physics
(1995) - et al.
Preoperative concurrent 5FU infusion, mitomycin and pelvic radiation therapy in tethered and fixed rectal carcinoma
International Journal of Radiation Oncology, Biology, Physics
(1993) - et al.
Conti Preoperative 5-FU, low-dose leucovorin, and radiation therapy for locally advanced and unresectable rectal cancer
International Journal of Radiation Oncology, Biology, Physics
(1997) Adjuvant versus neoadjuvant combined modality treatment for locally advanced rectal cancerfirst results of the German rectal cancer study (CAO/ARO/AIO-94)
International Journal of Radiation Oncology, Biology, Physics
(2003)- et al.
Cancer statistics 2003. CA—Cancer
Journal for Clinicians
(2003) - et al.
Annual report to the nation on the states of cancer, 1975–2003, featuring the uses of surveillance data for cancer prevention and control
Journal of the National Cancer Institute
(2000) - et al.
The relationship between different staging methods and survival in colorectal carcinoma
Diseases of the Colon and Rectum
(1985)
Adjuvant therapy of colorectal cancer
Why we still don’t know. JAMA
Postoperative adjuvant chemotherapy or BCG for colon cancerresults from NSABP protocol C-01
Journal of the National Cancer Institute
Efficacy of prolonged intermittent therapy with combined 5-fluorouracil and methyl-CCNU following resection for carcinoma of the large bowel
A Veterans Administration Surgical Oncology Group Report. Cancer
Adjuvant therapy in large bowel adenocarcinomalong-term results of a Southwest Oncology Group Study
Journal of Clinical Oncology
Sequential chemoimmunotherapy of colorectal cancerevaluation of methotrexate, Baker's Antifol and levamisole
Cancer
A controlled evaluation of recent approaches to biochemical modulation or enhancement of 5-fluorouracil therapy in colorectal carcinoma
Journal of Clinical Oncology
Levamisole in the treatment of canceranything new? (Review)
Anticancer Research
Surgical adjuvant therapy of large-bowel carcinomaan evaluation of levamisole and the combination of levamisole and fluorouracil. The North Central Cancer Treatment Group and the Mayo Clinic
Journal of Clinical Oncology
Fluorouracil plus levamisole as effective adjuvant therapy after resection of stage III colon carcinomaa final report
Annals of Internal Medicine
AXISa suitable case treatment
British Journal of Cancer
The benefit of leucovorin-modulated fluorouracil as postoperative adjuvant therapy for primary colon cancerresults from National Surgical Adjuvant Breast and Bowel Project protocol C-03
Journal of Clinical Oncology
Controlled trial of fluorouracil and low-dose leucovorin given for 6 months as postoperative adjuvant therapy for colon cancer
Journal of Clinical Oncology
Prospectively randomized trial of postoperative adjuvant chemotherapy in patients with high-risk colon cancer
Journal of Clinical Oncology
Clinical trial to assess the relative efficacy of fluorouracil and leucovorin, fluorouracil and levamisole, and fluorouracil, leucovorin, and levamisole in patients with Dukes’ B and C carcinoma of the colonresults from National Surgical Adjuvant Breast and Bowel Project C-04
Journal of Clinical Oncology
Fluorouracil (Fu), leucovorin (Lv) and levamisole (Lev) adjuvant therapy for colon cancerfive-year final report of Int-0089
Proceedings of the American Society of Clinical Oncology
Adjuvant chemotherapy with 5-fluorouracil, L-folinic acid and levamisole for patients with colorectal cancernon-randomised comparison of weekly versus four-weekly schedules—less pain, same gain QUASAR Colorectal Cancer Study Group
Annals of Oncology
Adjuvant cytotoxic liver perfusion for colorectal cancer
British Journal of Surgery
Adjuvant therapy of Dukes’ A, B, and C adenocarcinoma of the colon with portal-vein fluorouracil hepatic infusionpreliminary results of National Surgical Adjuvant Breast and Bowel Project Protocol C-02
Journal of Clinical Oncology
Adjuvant portal-vein infusion of fluorouracil and heparin in colorectal cancera randomised trial. European Organisation for Research and Treatment of Cancer Gastrointestinal Tract Cancer Cooperative Group, the Gruppo Interdisciplinare Valutazione Interventi in Oncologia, and the Japanese Foundation for Cancer Research
Journal of the National Cancer Institute
For the ACOI/GIVIO/GISCAD Investigators. Randomized trial of intraportal and/or systematic adjuvant chemotherapy in patients with colon carcinoma
Journal of the National Cancer Institute
Adjuvant 5-fluorouracil and leucovorin with or without interferon alfa-2a in colon carcinomaNational Surgical Adjuvant Breast and Bowel Project protocol C-05
Journal of the National Cancer Institute
Monoclonal antibody therapy for resected Dukes’ C colorectal cancerseven-year outcome of a multicenter randomized trial
Journal of Clinical Oncology
Cited by (14)
Anticancer activity of “Trigno M”, extract of Prunus spinosa drupes, against in vitro 3D and in vivo colon cancer models
2019, Biomedicine and PharmacotherapyCitation Excerpt :The cytotoxicity results of Trigno M on the HCT116 line were confirmed by scanning electron microscopy images (Fig. 3). 5-FU, a fluoro-pyrimidine analogue, widely used for the treatment of this type of cancer was chosen as chemotherapeutic to compare it with the cytotoxic effect of Trigno M [19]. Unfortunately, the mechanism of 5-FU resistance and induction of cell metastasis often occurred and resulted in poor outcome for the patients [31].
LINC01123 facilitates proliferation, invasion and chemoresistance of colon cancer cells
2020, Bioscience Reports