The benefit of leucovorin-modulated fluorouracil as postoperative adjuvant therapy for primary colon cancer: results from National Surgical Adjuvant Breast and Bowel Project protocol C-03.

Wolmark, Norman; Rockette, Howard E.; Fisher, Bernard; Wickerham, D. Lawrence; Redmond, Carol; Fisher, Edwin R.; Jones, Judy; Mamounas, Eleftherios P.; Ore, Liora; Petrelli, Nicholas J.

doi:10.1200/jco.1993.11.10.1879

Cited by 625 publications

(249 citation statements)

References 17 publications

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“…Unfortunately, steady-state plasma 5FU levels do not correlate with toxicity (Jodrell et al, 2001) and hence pharmacokinetic monitoring is not used to identify patients who are at increased risk of toxicity (Tebbutt et al, 2000). In randomised controlled trials, dose reductions are common after the first two cycles and 15 -30% of patients fail to complete chemotherapy (Wolmark et al, 1993;O'Connell et al, 1997;Poplin et al, 2005). The relationship between systemic exposure and treatment efficacy has not been demonstrated, however, and can only be ascertained by conducting prospective randomised studies that compare a targeted dose adjustment to a fixed dose (Milano et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

Failure to complete adjuvant chemotherapy is associated with adverse survival in stage III colon cancer patients

et al. 2007

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Two recent North American studies have shown that completion of 5-fluorouracil (5FU)-based adjuvant chemotherapy is a major prognostic factor for the survival of elderly stage III colon cancer patients. The aim of the present study was to confirm this finding in a population-based series from Australia. The study cohort comprised 851 stage III colon cancer patients treated by surgery alone and 461 who initiated the Mayo chemotherapy regime. One-third of patients who initiated chemotherapy failed to complete more than three cycles of treatment. Independent predictors for failure to complete were treatment in district or rural hospitals, low socioeconomic index and treatment by a low-volume surgeon. Patients who failed to complete chemotherapy showed worse cancer-specific survival compared not only to those who completed treatment (HR ¼ 2.24; 95% confidence interval (CI) (1.66 -3.03), Po0.001) but also to those treated by surgery alone (HR ¼ 1.37; 95% CI (1.09 -1.72), P ¼ 0.008). The current and previous studies demonstrate the importance of completing adjuvant 5-FU-based chemotherapy for colon cancer. Further prospective studies are required to identify better the physiological and socioeconomic factors responsible for failure to complete chemotherapy so that appropriate improvements in health service delivery can be made.

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Section: Discussionmentioning

confidence: 99%

Failure to complete adjuvant chemotherapy is associated with adverse survival in stage III colon cancer patients

et al. 2007

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“…Since the 1990s, chemotherapy using 5-fluorouracil and leucovorin (5-FU/LV) has become standard treatment for stage III colon cancer after successful surgery. 3,4 However, this chemotherapy is still insufficient for patients at a high risk to recurrence who have biologically aggressive tumors, and the need to improve the outcome in such patients has increased the interest in developing more intensive or more targeted therapeutic strategies.It has been shown that solid tumor growth beyond a certain size requires neovascularization to supply the tumor with oxygen and nutrients. 5 In other words, without neovascularization, micrometastasis cannot grow.…”

mentioning

confidence: 99%

Efficacy of the MMP inhibitor MMI270 against lung metastasis following removal of orthotopically transplanted human colon cancer in rat

Osuga

Matono

Nakajima

et al. 2005

Intl Journal of Cancer

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We have investigated the antitumor effects of synthetic MMP inhibitor MMI270 against postoperative lung metastasis from colon cancer in nude rat. The KM12SM human colon cancer cells were injected into the cecal wall, and at 5 weeks after the injection, the cecum was removed including the tumor. Then, 30 mg/kg of MMI270 was administered perorally twice per day for 2 or 4 weeks, either immediately after removal or after week 2 after the removal. At week 7 after the removal, lung metastasis was significantly inhibited by the early administration of MMI270 immediately after the tumor removal but not by the late administration. The survival rates were significantly higher in the rats treated by early administration of MMI270 compared to the survival rate in untreated rats. Moreover, no lung metastasis was detected in some rats with 24-weeks' survival treated by early administration. Lower microvessel density, lower PCNA Index and higher Apoptotic Index in the lung metastases of the rats treated with MMI270 were found compared to those in untreated rats. A beneficial effect of by early administration of MMI270 against postoperative lung metastases may be expected through inhibiting neovascularization of metastases in nude rat. ' 2005 Wiley-Liss, Inc.Key words: preclinical lung metastases model; angiogenesis; apoptosis; postoperative adjuvant therapy Colorectal cancer remains one of the major causes of cancer death worldwide. The mainstay of treatment for colorectal cancer with curative intent is surgical resection. However, recurrences to the liver or lung may occur in some patients even after a potentially curative operation. 1 For instance, the overall 5-year-survival rate for stage III cancer is approximately 60 % 2 due to postoperative recurrences even if the patients receive adjuvant chemotherapy. It is thought that the development of distant metastases depends on the spread of cancer cells from the primary tumor and that micrometastases already established prior to primary tumor resection appear as recurrent tumors after the operation. Therefore, to improve the postoperative prognosis of patients with colorectal cancer, effective adjuvant therapies against the micrometastases such as chemotherapy and immunotherapy should be considered. Since the 1990s, chemotherapy using 5-fluorouracil and leucovorin (5-FU/LV) has become standard treatment for stage III colon cancer after successful surgery. 3,4 However, this chemotherapy is still insufficient for patients at a high risk to recurrence who have biologically aggressive tumors, and the need to improve the outcome in such patients has increased the interest in developing more intensive or more targeted therapeutic strategies.It has been shown that solid tumor growth beyond a certain size requires neovascularization to supply the tumor with oxygen and nutrients. 5 In other words, without neovascularization, micrometastasis cannot grow. Therefore, it has been suggested that antiangiogenic therapy is effective against various solid tumors by inhibiting neovascularizat...

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“…While adjuvant radio-and chemo-therapy have improved recurrence-free survival (O'Connell and Gunderson, 1992;Wolmark et al, 1993;Kohnewompner et al, 1994;Schmoll, 1994), these combinations fail to have a significant effect either in those patients who present with Dukes' stage B disease, or on overall patient survival. Since only a minority of patients benefit from the adjuvant treatment modalities, better selection of those at high risk of recurrence, who would gain the major benefits from adjuvant treatment is required.…”

mentioning

confidence: 99%

Transforming growth factor β 1 expression in human colorectal tumours: an independent prognostic marker in a subgroup of poor prognosis patients

Robson

Anderson²,

James³

et al. 1996

Br J Cancer

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Summary Members of the transforming growth factor ,B (TGF-fl family, in particular TGF-,B1, are some of the most potent inhibitory growth factors in a variety of cell types. Resistance to TGF-f,l-induced growth inhibition is frequently observed in colorectal carcinomas and is associated with tumour progression. Perturbations of TGF-,B1 expression and function, therefore, may contribute to the loss of some constraints on tumour cell growth. In this study we have examined the expression of TGF-f,l and its precursor latencyassociated peptide (LAP)-TGF-f, in human colorectal tumours using immunohistochemical techniques. In 86% of the tumours the LAP-TGF-,B complex was present in both the stromal and epithelial cells, whereas the mature TGF-fll peptide was expressed in the glandular epithelium of 58.3% of these tumours. Intense staining for TGF-,B1 was positively associated with advanced Dukes' stage. Furthermore, there was a significant correlation between the presence of TGF-f,l in the tumours and a shorter post-operative survival. This was most significant in a subgroup of patients who had received only a palliative operation. These results suggest that TGF-,B1 expression may be useful as an independent prognostic indicator for a subgroup of patients who have a particularly poor prognosis.

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The benefit of leucovorin-modulated fluorouracil as postoperative adjuvant therapy for primary colon cancer: results from National Surgical Adjuvant Breast and Bowel Project protocol C-03.

Cited by 625 publications

References 17 publications

Failure to complete adjuvant chemotherapy is associated with adverse survival in stage III colon cancer patients

Failure to complete adjuvant chemotherapy is associated with adverse survival in stage III colon cancer patients

Efficacy of the MMP inhibitor MMI270 against lung metastasis following removal of orthotopically transplanted human colon cancer in rat

Transforming growth factor β 1 expression in human colorectal tumours: an independent prognostic marker in a subgroup of poor prognosis patients

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