Elsevier

Surgical Oncology

Volume 13, Issues 2–3, August–November 2004, Pages 63-73
Surgical Oncology

Adjuvant treatment of colorectal cancer

https://doi.org/10.1016/j.suronc.2004.09.008Get rights and content

Abstract

Colorectal cancer is one of the most frequent causes of cancer deaths. Survival for locoregional colorectal cancer is about 70% overall and 30–60% in stage III patients. Several randomized trials have shown that adjuvant chemotherapy can increase this survival rate. 5-Fluorouracil-based chemotherapy is strongly recommended in this context. There are still some questions about the setting in which patients should be treated as well as the optimal treatment. New data for different schedules and combinations are now available. Physicians have to choose between the different options now available to offer the best treatment to their patients. This Review analyses the current options for adjuvant therapy in colon and rectal 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)

  • NIH Consensus Conference. Adjuvant therapy for patients with colon and rectal cancer. JAMA...
  • M. Buyse et al.

    Adjuvant therapy of colorectal cancer

    Why we still don’t know. JAMA

    (1988)
  • N. Wolmark et al.

    Postoperative adjuvant chemotherapy or BCG for colon cancerresults from NSABP protocol C-01

    Journal of the National Cancer Institute

    (1988)
  • Gastrointestinal Study Group. Adjuvant therapy of colon cancer—results of a prospectively randomized trial. New England...
  • G.A. Higgins et al.

    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

    (1984)
  • F.J. Panettiere et al.

    Adjuvant therapy in large bowel adenocarcinomalong-term results of a Southwest Oncology Group Study

    Journal of Clinical Oncology

    (1988)
  • A.Y. Bedikian et al.

    Sequential chemoimmunotherapy of colorectal cancerevaluation of methotrexate, Baker's Antifol and levamisole

    Cancer

    (1978)
  • T.R. Buroker et al.

    A controlled evaluation of recent approaches to biochemical modulation or enhancement of 5-fluorouracil therapy in colorectal carcinoma

    Journal of Clinical Oncology

    (1985)
  • M. De Brabander et al.

    Levamisole in the treatment of canceranything new? (Review)

    Anticancer Research

    (1992)
  • J.A. Laurie et al.

    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

    (1989)
  • C.G. Moertel et al.

    Fluorouracil plus levamisole as effective adjuvant therapy after resection of stage III colon carcinomaa final report

    Annals of Internal Medicine

    (1995)
  • R. Gray et al.

    AXISa suitable case treatment

    British Journal of Cancer

    (1991)
  • N. Wolmark et al.

    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

    (1993)
  • International Multicentre Pooled Analysis of Colon Cancer Trials (IMPACT) investigators. Efficacy of adjuvant...
  • M.J. O’Connell et al.

    Controlled trial of fluorouracil and low-dose leucovorin given for 6 months as postoperative adjuvant therapy for colon cancer

    Journal of Clinical Oncology

    (1997)
  • M.J. O’Connell et al.

    Prospectively randomized trial of postoperative adjuvant chemotherapy in patients with high-risk colon cancer

    Journal of Clinical Oncology

    (1998)
  • N. Wolmark et al.

    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

    (1999)
  • D.G. Haller et al.

    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

    (1998)
  • QUASAR Collaborative Group. Comparison of fluorouracil with additional levamisole, higher-dose folinic acid, or both,...
  • D.J. Kerr et al.

    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

    (2000)
  • I. Taylor et al.

    Adjuvant cytotoxic liver perfusion for colorectal cancer

    British Journal of Surgery

    (1979)
  • N. Wolmark et al.

    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

    (1990)
  • Swiss Group for Clinical Cancer Research (SAKK). Long-term results of single course of adjuvant intraportal...
  • Liver Infusion Meta-Analysis Group. Portal vein Chemotherapy for colorectal cancer: a meta-analysis of 4000 patients in...
  • P. Rougier et al.

    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

    (1997)
  • AXIS Collaborators. Intraportal 5FU and perioperative radiotherapy in the adjuvant treatment of colorectal cancer-3681...
  • R. Labianca et al.

    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

    (2004)
  • N. Wolmark et al.

    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

    (1998)
  • G. Riethmuller et al.

    Monoclonal antibody therapy for resected Dukes’ C colorectal cancerseven-year outcome of a multicenter randomized trial

    Journal of Clinical Oncology

    (1998)
  • 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 Pharmacotherapy
      Citation 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].

    View all citing articles on Scopus
    View full text