Fluorouracil plus Levamisole as Effective Adjuvant Therapy after Resection of Stage III Colon Carcinoma: A Final Report

Moertel, Charles G.; Fleming, Thomas R.; Macdonald, John S.; Haller, Daniel G.; Laurie, John A.; Tangen, Catherine M.; Ungerleider, James S.; Emerson, William A.; Tormey, Douglass C.; Glick, John H.; Veeder, Michael H.; Mailliard, James A.

doi:10.7326/0003-4819-122-5-199503010-00001

Cited by 842 publications

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“…No clear trends were apparent in patients with Dukes' B2 disease. These results were confirmed in a later report after a median follow-up period of 6.5 years (Moertel et al, 1995 (Machover et al, 1986)] for 5 days every 28 days for six cycles. Of the 1493 evaluable patients, 736 were in the adjuvant treatment group and 757 were in the control (surgery only) group.…”

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confidence: 69%

The establishment of a large collaborative trial programme in the adjuvant treatment of colon cancer

Wils

1998

Br J Cancer

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Summary After many years, during which the assumption prevailed that adjuvant chemotherapy was of no benefit in patients with resectable adenocarcinoma of the colon, findings of several large USA studies published from the late 1980s have caused a marked shift in surgical and medical opinion. Although results in patients with Dukes' B disease have not shown any clear benefit, the efficacy of adjuvant chemotherapy has nevertheless been shown in those with Dukes' C colon cancer. As a result, the Mayo regimen of 5-fluorouracil (5-FU) with low-dose leucovorin (LV) has become accepted as standard adjuvant therapy in these patients. However, the disadvantages associated with standard 5-FU-based treatment, particularly those relating to its toxicity and inconvenience of administration, have generated interest in other regimens and agents. The novel direct and specific thymidylate synthase inhibitor raltitrexed ('Tomudex') has been associated with similar objective response rates to standard therapy with 5-FU plus LV in patients with advanced colorectal cancer. In addition, raltitrexed has an attractive tolerability profile compared with that of 5-FU plus LV (specifically with respect to lower incidences of mucositis and leucopenia), and the simple 3-weekly administration schedule may be considered more convenient by many patients and may reduce healthcare resource consumption. To investigate alternatives to the Mayo regimen in the adjuvant treatment of Dukes' C adenocarcinoma of the colon, two large European trials have been set up: (1) PETACC-1 (first Pan-European Trial for Adjuvant Treatment of Colon Cancer), to compare raltitrexed with the Mayo regimen of 5-FU and low-dose LV; (2) PETACC-2 (second Pan-European Trial), to compare the Mayo regimen with three regimens in which 5-FU is given by prolonged infusion. These trials will provide valuable international data to add to those from the USA and will assess the place of raltitrexed in the adjuvant treatment of Dukes' C colon cancer. They will also compare directly for the first time infusional and bolus 5-FU regimens in the adjuvant setting.

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supporting

confidence: 69%

The establishment of a large collaborative trial programme in the adjuvant treatment of colon cancer

Wils

1998

Br J Cancer

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“…Ever since a randomized trial in the early nineties showed that patients with stage III colon carcinoma treated with adjuvant chemotherapy had a significant survival benefit [33], chemotherapy after surgery has been the standard of care for stage III patients with an adequate performance status. [10] However, not all patients with stage III disease receive adjuvant chemotherapy.…”

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confidence: 99%

Disparities in quality of care for colon cancer between hospitals in the Netherlands

Elferink

Wouters

Krijnen

et al. 2010

European Journal of Surgical Oncology (EJSO)

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“…In CRC the prognostic predictor is tumour stage based on histopathologic examination of the resected specimen combined with perioperative findings (Dukes and Bussey, 1958;Lindmark et al, 1994;Fleming et al, 1997). It has been shown that adjuvant chemotherapy reduces the relative mortality rate by one-third in patients operated for colon cancer in Dukes' Stage C (any TN1-2M0, Stage III) (Moertel et al, 1995;Fleming et al, 1997). Adjuvant chemotherapy is not routinely given to patients of Dukes' Stage A (T1-2N0M0, Stage I) or Stage B (T3-4N0M0, Stage II) although a substantial number of patients with Dukes' Stage B tumour will die from tumour recurrences.…”

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confidence: 99%

Biomarker selection for detection of occult tumour cells in lymph nodes of colorectal cancer patients using real-time quantitative RT–PCR

et al. 2006

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Accurate identification of lymph node involvement is critical for successful treatment of patients with colorectal carcinoma (CRC). Real-time quantitative RT -PCR with a specific probe and RNA copy standard for biomarker mRNA has proven very powerful for detection of disseminated tumour cells. Which properties of biomarker mRNAs are important for identification of disseminated CRC cells? Seven biomarker candidates, CEA, CEACAM1-S/L, CEACAM6, CEACAM7-1/2, MUC2, MMP7 and CK20, were compared in a test-set of lymph nodes from 51 CRC patients (Dukes' A -D) and 10 controls. Normal colon epithelial cells, primary tumours, and different immune cells were also analysed. The biomarkers were ranked according to: (1) detection of haematoxylin/eosin positive nodes, (2) detection of Dukes' A and B patients, who developed metastases during a 54 months follow-up period and (3) identification of patients with Dukes' C and D tumours using the highest value of control nodes as cutoff. The following properties appear to be of importance; (a) no expression in immune cells, (b) relatively high and constant expression in tumour tissue irrespective of Dukes' stage and (c) no or weak downregulation in tumours compared to normal tissue. CEA fulfilled these criteria best, followed by CK20 and MUC2.

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Fluorouracil plus Levamisole as Effective Adjuvant Therapy after Resection of Stage III Colon Carcinoma: A Final Report

Abstract: Fluorouracil plus levamisole is tolerable adjuvant therapy to surgery; it has been confirmed to substantially increase cure rates for patients with high-risk (stage III) colon cancer. It should be considered standard treatment for all such patients not entered into clinical trials.

Cited by 842 publications

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The establishment of a large collaborative trial programme in the adjuvant treatment of colon cancer

The establishment of a large collaborative trial programme in the adjuvant treatment of colon cancer

Disparities in quality of care for colon cancer between hospitals in the Netherlands

Biomarker selection for detection of occult tumour cells in lymph nodes of colorectal cancer patients using real-time quantitative RT–PCR

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