Summary
Every year, 31 230 men and women are diagnosed with colorectal carcinoma, and up to 60% of these will ultimately develop advanced disease. However, there is little information to identify which patients are most likely to benefit from palliative chemotherapy. This analysis is unique in evaluating how the site of metastasis influences response and survival. A database of 497 patients treated within randomized clinical trials using 5-Fluorouracil (5FU)-based chemotherapy at the Royal Marsden Hospital was analysed. The potential for site of metastasis as a predictive variable for response to chemotherapy and survival was examined, in addition to other clinical parameters. The presence of liver metastases was a better predictor for overall response than either performance status or number of metastatic sites on presentation. Probability of response was significantly decreased by a raised serum carcinoembryonic antigen (CEA) and presence of peritoneal metastases. In liver metastases, a normal serum albumin was as significant a predictor for response as good performance status. The most important predictor for survival was initial performance status. The number of metastatic sites on presentation had no influence on survival. Site of metastasis can predict for response to 5FU-based chemotherapy and patients should be stratified according to the involved site of metastasis in the future.
Similar content being viewed by others
Article PDF
Change history
16 November 2011
This paper was modified 12 months after initial publication to switch to Creative Commons licence terms, as noted at publication
References
Advanced Colorectal Cancer Meta-Analysis Project: (1992). Modulation of Fluorouracil by leucovorin in patients with advanced colorectal cancer: Evidence in terms of response rate. J Clin Oncol 10: 896–903.
Allen-Mersh, T. G., Earlam, S., Fordy, C., Abrams, K. & Houghton, J. (1994). Quality of life and survival with continuous hepatic-artery floxuridine infusion for colorectal liver metastases. Lancet 344: 1255–1260.
Buroker, T., O’Connnell, M., Wieand, S., Krook, J. E., Gerstner, J. B., Mailliard, J. A., Schaefer, P. L., Levitt, R., Kardinal, C. G. & Gesme, D. H. (1994). Randomized comparison of two schedules of fluorouracil and leucovorin in the treatment of advanced colorectal cancer. J Clin Oncol 12: 14–20.
Cancer Research Campaign: (1998). Factsheet 1.3 (incidence of cancer in males in UK) and 1.4 (incidence of cancer in females in UK)
Chang, A. E., Steinberg, S. M., Culnane, M. & White, D. E. (1989). Determinants of survival in patients with unresectable colorectal liver metastases. J Surg Oncol 40: 245–251.
Conti, J. A., Kemeny, N. E., Saltz, L. B., Andre, A. M., Grossano, D. D. & Bertino, J. R. (1995). Continuous infusion fluorouracil/leucovorin and bolus mitomycin C as a salvage regimen for patients with advanced colorectal cancer. Cancer 75: 769–774.
Finan, P. J., Marshall, R. J., Cooper, E. H. & Giles, G. R. (1985). Factors affecting survival in patients presenting with synchronous hepatic metastases from colorectal cancer: a clinical and computer analysis. Br J Surg 72: 373–377.
Fountzilas, G., Gossios, K., Zisiadis, A., Svarna, E., Skarlos, D. & Pavlidis, N. (1996). Prognostic variables in patients with advanced colorectal cancer treated with fluorouracil and leucovorin-based chemotherapy. Med & Ped Oncol 26: 305–317.
Gorlick, R., Metzger, R., Danenberg, K. D., Salonga, D., Miles, J. S., Longo, G. S. A., Fu, J., Banerjee, D., Klimstra, D., Jhanwar, S., Danenberg, P. V., Kemeny, N. & Bertino, J. R. (1998). Higher levels of thymidylate synthase gene expression are observed in pulmonary as compared with hepatic metastases of colorectal adenocarcinoma. J Clin Oncol 16: 1465–1469.
Hill, M., Norman, A., Cunningham, D., Findlay, M., Watson, M., Nicolson, V., Webb, A., Middleton, G., Ahmed, F., Hickish, T., Nicolson, M., O’Brien, M., Iveson, T., Iveson, A. & Evans, C. (1995a). Impact of protracted venous infusion fluorouracil with or without interferon Alfa-2b on tumor response, survival and quality of life in advanced colorectal cancer. J Clin Oncol 13: 2317–2323.
Hill, M., Norman, A., Cunningham, D., Findlay, M., Nicolson, V., Hill, A., Iveson, A., Evans, C., Joffe, J., Nicolson, M. & Hickish, T. (1995b). Royal Marsden phase III trial of Fluorouracil with or without interferon Alfa-2b in advanced colorectal cancer. J Clin Oncol 13: 1297–1302.
Johnston, P. G., Lenz, H. J., Leichman, C. G., Danenberg, K. D., Allegra, C. J., Danenberg, P. V. & Leichman, L. (1995). Thymidylate synthase gene and protein expression correlate and are associated with response to 5-fluorouracil in human colorectal and gastric tumors. Cancer Res 55: 1407–1412.
Kosmidis, P. A., Tsavaris, N., Skarlos, D., Theocharis, D., Samantas, E., Pavlidis, N., Briassoulis, E. & Fountzilas, G. (1996). Fluorouracil and leucovorin with or without interferon Alfa-2b in advanced colorectal cancer: analysis of a prospective randomized phase III trial. J Clin Oncol 14: 2682–2687.
Kouri, M., Pyrhonen, S. & Kuusela, P. (1992). Elevated CA19-9 as the most significant prognostic factor in advanced colorectal carcinoma. J Surg Oncol 49: 78–85.
Kouri, M., Nordling, S., Kuusela, P. & Pythonen, S. (1993). Poor prognosis associated with elevated serum CA 19-9 level in advanced colorectal carcinoma, independent of DNA ploidy or SPF. Eur J Cancer 29A: 1691–1696.
Leichman, C. G., Lenz, H. J., Leichman, L., Danenberg, K., Baranda, J., Groshen, S., Bowsell, W., Metzger, R., Tan, M. & Danenberg, P. V. (1997). Quantitation of intratumoral thymidylate synthase expression predicts for disseminated colorectal cancer response and resistance to protracted-infusion fluorouracil and weekly leucovorin. J Clin Oncol 15: 3223–3229.
Mayer, R. J. (1992). Chemotherapy for metastatic colorectal cancer. Cancer 70: 1414–1424.
Meta-analysis Group In Cancer: (1998). Efficacy of intravenous continuous infusion of fluorouracil compared with bolus administration in advanced colorectal cancer. J Clin Oncol 16: 301–308.
Miller, A. B., Hoogstraaten, B., Staquet, M. & Winkler, A. (1981). Reporting results of cancer treatment. Cancer 47: 207–214.
Nordic Gastrointestinal Tumour Adjuvant Therapy Group: (1992). Expectancy or primary chemotherapy in patients with advanced asymptomatic colorectal cancer: a randomized trial. J Clin Oncol 10: 904–911.
Poon, M. A., O’Connell, M. J., Moertel, C. G., Wieand, H. S., Cullinan, S. A., Everson, L. K., Krook, J. E., Mailliard, J. A., Laurie, J., Tschetter, L. K. & Wiesenfeld, M. (1989). Biochemical modulation of Fluorouracil: evidence of significant improvement of survival and quality of life in patients with advanced colorectal carcinoma. J Clin Oncol 7: 1407–1418.
Recchia, F., Nuzzo, A., Lalli, A., Lombardo, M., Di-Lullo, L., Fabiani, F., Fanini, R., Venturoni, L., Torchio, P. & Peretti, G. (1996). Randomized trial of 5-Fluorouracil and high-dose folinic acid with or without alpha-2b interferon in advanced colorectal cancer. Am J Clin Oncol 19: 301–304.
Ross, P., Norman, A., Cunningham, D., Webb, A., Iveson, T., Padhani, A., Prendiville, J., Watson, M., Massey, A. & Oates, J. (1997). A prospective randomised trial of protracted venous infusion (PVI) 5-FU with or without mitomycin C (MMC) in advanced colorectal cancer. Annals Oncol 8: 995–1001.
Scheithauer, W., Rosen, H., Kornek, G. V., Sebesta, C. & Depisch, D. (1993). Randomised comparison of combination chemotherapy plus supportive care with supportive care alone in patients with metastatic colorectal cancer. BMJ 306: 752–755.
Seymour, M. T., Slevin, M. L., Kerr, D. J., Cunningham, D., James, R. D., Ledermann, J. A., Perren, T. J., McAdam, W. A., Harper, P. G., Neoptolemos, J. P., Nicholson, M., Duffy, A. M., Stephens, R. J., Stenning, S. P. & Taylor, I. (1996). Randomized trial assessing the addition of interferon alpha-2a to fluorouracil and leucovorin in advanced colorectal cancer. J Clin Oncol 14: 2280–2288.
Stangl, R., Altendorf-Hofmann, A., Charnley, R. & Scheele, J. (1994). Factors influencing the natural history of colorectal liver metastases. Lancet 343: 1405–1410.
Steinberg, J., Erlichman, C., Gadalla, T., Fine, S. & Wong, A. (1992). Prognostic factors in patients with metastatic colorectal cancer receiving 5-fluorouracil and folinic acid. Eur J Cancer 28A(ii): 1817–1820.
Webb, A., Scott-Mackie, P., Cunningham, D., Norman, A., Andreyev, J., O’Brien, M. & Bensted, J. (1995). The prognostic value of CEA, bHCG, AFP, CA125, CA19-9 and C-erb B-2, bHCG immunohistochemistry in advanced colorectal cancer. Annals Oncol 6: 581–587.
Yeh, K. H., Shun, C. T., Chen, C. L., Lin, J. T., Lee, W. J., Lee, P. H., Chen, Y. C. & Cheng, A. L. (1998). High expression of thymidylate synthase is associated with the drug resistance of gastric carcinoma to high dose 5-fluorouracil-based systemic chemotherapy. Cancer 82: 1626–1631.
Author information
Authors and Affiliations
Rights and permissions
From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
About this article
Cite this article
Assersohn, L., Norman, A., Cunningham, D. et al. Influence of metastatic site as an additional predictor for response and outcome in advanced colorectal carcinoma. Br J Cancer 79, 1800–1805 (1999). https://doi.org/10.1038/sj.bjc.6990287
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.bjc.6990287
Keywords
This article is cited by
-
The implication of BRAF mutation in advanced colorectal cancer
Irish Journal of Medical Science (1971 -) (2022)
-
Immunohistochemical expression of β-catenin, Ki67, CD3 and CD18 in canine colorectal adenomas and adenocarcinomas
BMC Veterinary Research (2021)
-
Targeting BRAF mutant metastatic colorectal cancer: clinical implications and emerging therapeutic strategies
Targeted Oncology (2015)
-
Rate of Pulmonary Metastasis Varies with Location of Rectal Cancer in the Patients Undergoing Curative Resection
World Journal of Surgery (2015)
-
Role of Chemotherapy in Peritoneal Carcinomatosis in Metastatic Colorectal Cancer
Current Colorectal Cancer Reports (2013)