Skip to main content

Advertisement

SpringerLink
Log in

Adjuvant therapy for colorectal cancer

The EORTC experience and a review of the literature

  • Published:
Diseases of the Colon & Rectum

Abstract

In spite of the improvements in surgical techniques and intensive care therapy, no appreciable improvement in the prognosis for patients with colorectal cancer has been made in recent years. Several types of adjuvant treatment, including radiotherapy, chemotherapy, and immunotherapy, have therefore been proposed and used in clinical trials, mainly in the United States and western Europe. The results obtained by the Gastrointestinal Group of the European Organization for Research and Treatment of Cancer (EORTC), using preoperative radiation therapy with 3450 rads, are reported here; this therapy results in a reduction in the number of local recurrences and also appears to prolong the five-year survival period, although a longer follow-up is required to confirm this. According to the Gastrointestinal Tumor Study Group (GITSG), postoperative radiation therapy with chemotherapy seems to prolong the tumor-free interval in stages B2 and C when compared to surgery alone. Nonspecific immunotherapy does not appear to improve surgical results either in terms of local recurrences or survival. Some clinical trials suggest that systemic polychemotherapy benefit subgroups of patients with colorectal cancer. Toxicity is still very high, however; 5-FU is the more active and safe single agent but, due to the low response rate, it appears essential to identify new, more active drugs. Particular attention has been focused recently on prophylactic infusion chemotherapy of the liver, and clinical trials are now being made by several groups, including the EORTC. Preliminary results seem to show a reduced incidence of liver metastases in patients infused with 5-FU after radical surgery. Adjuvant therapy in colorectal cancer patients undergoing radical surgery has so far given encouraging results. Future results are awaited with optimism, but they must be achieved through prospective clinical trials conducted by well-organized cooperative groups.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Gerard A. Carcinoma of colon and rectum: prognostic factors and criteria of response. In: Staquet MJ. Cancer therapy: prognostic factors and criteria of response. New York: Raven Press, 1975: 199–227.

    Google Scholar 

  2. Lea JW IV, Covington K, McSwarn B, et al. Surgical experience with carcinoma of the colon and rectum. Ann Surg 1982;195: 600–7.

    Article  PubMed  Google Scholar 

  3. Axtell LM, Asire AJ, Myers MH. Cancer survival. Bethesda: NCI, 1976, report no 5, Cancer Seer Program.

    Google Scholar 

  4. Gill PG, Morris PJ. The survival of patients with colorectal cancer treated in a regional hospital. Br J Surg 1978;65:17–21.

    PubMed  CAS  Google Scholar 

  5. Clark DN, Jones PF, Needham CD. Outcome in colorectal carcinoma: saving-year study of a population. Br Med J 1980;280: 431–5.

    Article  Google Scholar 

  6. McDermott FT, Hughes ER, Pihl EA, Milne BJ. Changing survival prospect in carcinoma of the rectum. Br J Surg 1980;67: 775–80.

    PubMed  CAS  Google Scholar 

  7. Cass AW, Million RR, Pfaff WW. Patterns of recurrence following surgery alone for adenocarcinoma of the colon and rectum. Cancer 1976;37:2861–5.

    Article  PubMed  CAS  Google Scholar 

  8. Gilbert SG. Symptomatic local tumor failure following abdominoperineal resection. Int J Radiat Oncol Biol Phys 1978;4:801–6.

    PubMed  CAS  Google Scholar 

  9. Rao AR, Kagan AR, Chang PM, et al. Patterns of recurrence following curative resection alone for adenocarcinoma of rectum and sigmoid colon. Cancer 1981;48:1492–5.

    Article  PubMed  CAS  Google Scholar 

  10. Rich T, Gunderson LL, Lew R, et al. Patterns of recurrence of rectal cancer after potentially curative surgery. Cancer 1983;32: 1317–29.

    Article  Google Scholar 

  11. Mendenhall WM, Million RR, Pfaff WW. Patterns of recurrence of adenocarcinoma of the rectum and rectosigmoid treated with surgery alone: implications and treatment planning with adjuvant radiation therapy. Int J Radiat Oncol Biol Phys 1983;9:977–85.

    PubMed  CAS  Google Scholar 

  12. Pilipshen SJ, Heilweil M, Quan SH. Patterns of pelvic recurrence following definitive resection of rectal cancer. Cancer 1984;53: 1354–62.

    Article  PubMed  CAS  Google Scholar 

  13. Willett CG, Tepper JE, Cohen AM, et al. Failure patterns following curative resection of colonic carcinoma. Ann Surg 1984; 200:685–90.

    Article  PubMed  CAS  Google Scholar 

  14. Russel AH, Tong D, Dawson LE, et al. Adenocarcinoma of the proximal colon: sites of initial dissesmination and patterns of recurrence after surgery alone. Cancer 1984;53:360–7.

    Article  Google Scholar 

  15. Gunderson LL, Sosin H, Levitt S. Extrapelvic colon—areas of failure in reoperation series: implications for adjuvant therapy. Int J Radiat Oncol Biol Phys 1985;11:731–41.

    PubMed  CAS  Google Scholar 

  16. Burchenal JH. Adjuvant therapy—theory, practice, and potential. Caner 1976;37:46–57.

    Article  CAS  Google Scholar 

  17. Fisher ER, Turnbull RB. The cytological demonstration of significance of tumor cells in the mesenteric venous blood in patients with colorectal cancer. Surg Gynecol Obstet 1975;100:102–7.

    Google Scholar 

  18. Spratt JS, Spjut HJ. Prevalence and prognosis of individual clinical and pathologic variables associated with colorectal carcinoma. Cancer 1967;20:1976–85.

    Article  PubMed  Google Scholar 

  19. Talbot IC, Rietchie S, Leghton MH, Hugues AO, Bussey HJ, Morson BC. The clinical significance of invasion of veins by rectal cancer. Br J Surg 1980;67:439–42.

    PubMed  CAS  Google Scholar 

  20. Andrews JR. The radiobiology of human cancer radiotherapy. 2nd ed. Baltimore: University Park Press, 1978.

    Google Scholar 

  21. Hall EJ. Radiology for the radiologist. 2nd ed. New York: Harper & Row, 1978.

    Google Scholar 

  22. Fletcher GH. Clinical dose-response curves of human malignant epithelial tumours. Br J Radiol 1973;46:1–12.

    Article  PubMed  CAS  Google Scholar 

  23. Kligerman MM. Preoperative radiation therapy in rectal cancer. Cancer 1975;36:691–5.

    Article  PubMed  CAS  Google Scholar 

  24. Leaming RH, Stearns MW, Deddish MR. Preoperative irradiation in rectal cancer. Radiology 1961;77:257–63.

    PubMed  CAS  Google Scholar 

  25. Simbirsteva LP, Sneshko LP, Smirnov NM. Results of intensive combined therapy for carcinoma of the rectum. Kopr Onkol 1975;21:7–12.

    Google Scholar 

  26. Stevens KS Jr, Allen CV, Flecher WS. Preoperative radiotherapy for adenocarcinoma of the rectosigmoid. Cancer 1976;37:2866–74.

    Article  PubMed  Google Scholar 

  27. Pujol H, Solassol C, Gary-Bobo J, et al. La radioterapie preoperatoire des cancers du rectum, actualisation des resultats a propos de 159 cas. Chirurgie 1978;104:606–11.

    PubMed  CAS  Google Scholar 

  28. Stearns MW jr, Deddish MR, Quan SH. Preoperative roentgen therapy for cancer of the rectum. Surg Gynecol Obstet 1959;109: 225–9.

    PubMed  Google Scholar 

  29. Stearns MW Jr. Pre- or postoperative radiation in resectable tumours. In: Welvaart K, Blumgart LH, Kreuning J, eds. Colorectal cancer. The Hague: Leiden University Press, 1980:153–9.

    Google Scholar 

  30. Kligerman MM. Radiotherapy and rectal cancer. Cancer 1977; 39:896–900.

    Article  PubMed  CAS  Google Scholar 

  31. Higgins GA Jr, Conn JH, Jordan PH Jr, Humphrey EW, Roswit B, Keehn RJ. Preoperative radiotherapy for colorectal cancer. Ann Surg 1975;181:624–31.

    Article  PubMed  Google Scholar 

  32. Higgins GA, Humphrey EW, Dwight RW, Roswit B, Lyndon EE Jr, Keehn R. Preoperative radiation and surgery for cancer of the rectum. Veterans Administration Surgical Oncology Group Trial II. Cancer 1986;58:352–9.

    Article  PubMed  CAS  Google Scholar 

  33. Rider WD, Palmer JA, Mahoney LJ, Robertson CT. Preoperative irradiation in operable cancer of the rectum: report of the Toronto trial. Can J Surg 1977;20:335–8.

    PubMed  CAS  Google Scholar 

  34. Boulis-Wassif S, Gerard A, Loygue J, Camelot D, Buyse M, Duez N. Final results of a randomized trial on the treatment of rectal cancer with preoperative radiotherapy alone or in combination with 5-fluorouracil followed by radical surgery. Cancer 1984;53: 1811–8.

    Article  PubMed  CAS  Google Scholar 

  35. Second Report of an MRC Working Party. The evaluation of low dose preoperative x-ray therapy in the management of operable rectal cancer: results of a randomly controlled trial. Br J Surg 1984;71:21–5.

    Google Scholar 

  36. Gerard A, Berrod JL, Pene F, et al. Interim analysis of a phase III study on preoperative radiation therapy in resectable rectal carcinoma. Cancer 1985;55:2373–9.

    Article  PubMed  CAS  Google Scholar 

  37. Cedermark B, Theve NO, Rieger A, et al. Preoperative short-term radiotherapy in rectal cancer: a preliminary report of a prospective randomized study. Cancer 1985;15:1182–5.

    Article  Google Scholar 

  38. Gerard A, Berrod JL, Pene F, et al. Adjuvant preoperative radiotherapy and radical surgery as combined treatment in rectal cancer. EORTC Symposium on Gastrointestinal Tract Cancer Update on Combined Modality Therapy. Heidelberg, West Germany, May 29–30, 1986.

  39. Gunderson LL, Sosin H. Areas of failure found at reoperation (second or symptomatic look) following “curative surgery” for adenocarcinoma of the rectum. Cancer 1974;34:1278–92.

    Article  PubMed  CAS  Google Scholar 

  40. Gunderson LL. Combined irradiation and surgery for rectal and sigmoid carcinoma. Curr Probl Cancer 1976;1:40–53.

    Article  PubMed  CAS  Google Scholar 

  41. Russel JC, Welch JP. Operative management of radiation injuries of the intestinal tract. Am J Surg 1979;137:433–42.

    Article  Google Scholar 

  42. Ghossein NA, Samala EC, Alpert S, et al. Elective postoperative radiotherapy after incomplete resection of colorectal cancer. Dis Colon Rectum 1981;24:252–6.

    PubMed  CAS  Google Scholar 

  43. Mohiuddin M, Derdel J, Marks G, et al. Results of adjuvant radiation therapy in cancer of the rectum: Thomas Jefferson University Hospital experience. Cancer 1985;55:350–3.

    Article  PubMed  CAS  Google Scholar 

  44. Withers HR, Romsdahl MM. Postoperative radiotherapy for adenocarcinoma of the rectum and rectosigmoid. Int J Radiat Oncol Biol Phys 1967;2:1069.

    Google Scholar 

  45. Mendiondo OA, Wang CC, Welch JP, Donaldson GA. Postoperative radiotherapy in carcinomas of the rectum and distal sigmoid colon. Radiology 1976;119:673–6.

    PubMed  CAS  Google Scholar 

  46. Cohen Y, Honigman J, Robinson E. The treatment of rectosigmoid cancer by surgery, radiotherapy and chemotherapy. Digestion 1977;16:235–9.

    Google Scholar 

  47. Turner SS, Vieira EF, Ager DJ, et al. Elective postoperative radiotherapy for locally advanced colorectal cancer. Cancer 1977;40:105–8.

    Article  PubMed  CAS  Google Scholar 

  48. Hoskins RB, Gunderson LL, Dosoretz DE, et al. Adjuvant postoperative radiotherapy in carcinoma of the rectum and rectosigmoid. Cancer 1985;55:61–71.

    Article  PubMed  CAS  Google Scholar 

  49. Gastrointestinal Tumor Study Group. Prolongation of the disease-free interval in surgically treated rectal carcinoma. N Engl J Med 1985;23:1465–72.

    Google Scholar 

  50. Balslev I, Pedersen M, Teglbjaerg PS, et al. Postoperative radiotherapy in Dukes' B and C carcinoma of the rectum and rectosigmoid. Cancer 1986;58:22–8.

    Article  PubMed  CAS  Google Scholar 

  51. Gunderson LL, Dosoretz DE, Hedberg SE, et al. Low dose preoperative radiation surgery and elective postoperative radiation therapy for resectable rectum and rectosigmoid carcinoma. Cancer 1983;52:446–51.

    Article  PubMed  CAS  Google Scholar 

  52. Bayer I, Turani H, Lurie H, Chaimoff Ch. The sandwich approach—irradiation-surgery-irradiation in rectal cancer: four years' experience. Dis Colon Rectum 1985;28:222–4.

    PubMed  CAS  Google Scholar 

  53. Mrazek WK, Economou S, McDonald GO, Slaughter DP, Cole WP. Prophylactic and adjuvant use of chemotherapy in the surgical treatment of cancer. Acta Unio Int Cancrum 1964; 20:511–2.

    CAS  Google Scholar 

  54. Dwight RW, Higgins GA, Keehn RJ. Factors influencing survival after resection in cancer of the colon and rectum. Am J Surg 1969;117:512–22.

    Article  PubMed  CAS  Google Scholar 

  55. Dixon WJ, Longmire WP, Holden WD. Use of triethylenethio-phosphamide as an adjuvant to the surgical treatment of gastric and colorectal carcinoma: ten-year follow-up. Ann Surg 1970;1: 26–39.

    Google Scholar 

  56. Dwight RW, Humphrey EW, Higgins GA, Keehn RJ. FUDR as an adjuvant to surgery in cancer of the large bowel. J Surg Oncol 1973;5:243–9.

    PubMed  CAS  Google Scholar 

  57. Higgins GA, Humphrey EW, Juler GL, LeVeen HH, McCaughan J, Keehn RJ. Adjuvant chemotherapy in the surgical treatment of large bowel cancer. Cancer 1976;38:1461–7.

    Article  PubMed  CAS  Google Scholar 

  58. Grossi CE, Wolf WI, Nealon TF, Pastermack B, Ginzburg L, Rousselot LM. Intraluminal fluorouracil chemotherapy adjuvant to surgical procedures for resectable carcinoma of the colon and rectum. Surg Gynecol Obstet 1977;145:549–54.

    PubMed  CAS  Google Scholar 

  59. Lawrence WS, Tern JJ, Horsey JS, Brown PW, Romero C. Chemotherapy as an adjuvant to surgery for colorectal cancer: a follow-up report. Arch Surg 1978;113:164–8.

    PubMed  Google Scholar 

  60. Mansour EG, McIntyre JM, Johnson R, Lerner HJ, Muggia FM. Adjuvant studies in colorectal carcinoma: experience of the Eastern Cooperative Oncology Group (ECOG): preliminary report. In: Gerard A, ed. Progress and perspectives in the treatment of gastrointestinal tumors. Oxford: Pergamon Press, 1981:68–75.

    Google Scholar 

  61. Grage TB, Moss SE. Adjuvant chemotherapy in cancer of the colon and rectum: demonstration of effectiveness of prolonged 5-FU chemotherapy in a prospectively controlled randomized trial. Surg Clin North Am 1981;61:1321–9.

    PubMed  CAS  Google Scholar 

  62. Higgins GA, Amadeo JH, McElminney J, McCaughan JJ, Keehn R. Efficacy of prolonged intermittent therapy with combined 5-FU and MeCCNU following resection for carcinoma of the large bowel. Cancer 1984;53:1–8.

    Article  PubMed  Google Scholar 

  63. Gilbert JM, Hellmann K, Evans M, et al. Randomized trial of oral adjuvant razoxane (ICRF159) in resectable colorectal cancer: five-year follow-up. Br J Surg 1986;73:446–50.

    PubMed  CAS  Google Scholar 

  64. Hafstrom L, Rudestam CM, Domellof L, et al. A randomized trial of oral 5-fluorouracil versus placebo as adjuvant therapy in colorectal cancer Dukes' B and C: results after 5 years' observation time. Br J Surg 1985;75:138–41.

    Google Scholar 

  65. Panettiere FJ, Chen TT. Analysis of 626 patients entered on the SWOG large bowel adjuvant program. In: Salmon SE, Jones SE, eds. Adjuvant therapy of Cancer III. New York: Grune & Stratton, 1981:539–46.

    Google Scholar 

  66. Gastrointestinal Tumours Study Group. Adjuvant therapy of colon cancer: results of a prospectively randomized trial. N Engl J Med 1984;12:737–43.

    Google Scholar 

  67. Wolmark N, Fisher R, Wieand S, et al. Adjuvant chemotherapy in carcinoma of the colon: preliminary results from NSABP protocol C-01. Proc ASCO 1985;4:86.

    Google Scholar 

  68. Mavligit GM, Gutterman JU, Mulahy MA, et al. Adjuvant immunotherapy and chemo-immunotherapy in colorectal cancer (Dukes' class C): prolongation of disease-free interval and survival. Cancer 1977;40:2726–30.

    Article  PubMed  CAS  Google Scholar 

  69. Buyse M, Arnaud JP, Adloff M, Nordlinger B, Duez N. Double-blind phase III clinical trial of adjuvant levamisole vs control in resectable Dukes' C colon cancer: a study of the EORTC Gastrointestinal Tract Cancer Cooperative Group. EORTC Symposium on Gastrointestinal Tract Cancer Update on Combined Modality Therapy. Heidelberg, West Germany, May 29–30, 1986.

  70. Souter RG, Gibb PG, Morris PJ. A trial of nonspecific immunotherapy using systemic C parvum in treated patients with Dukes' B and C colorectal cancer. Br J Cancer 1982;45:506–12.

    PubMed  CAS  Google Scholar 

  71. Taylor I, Rowling GT, West C. Adjuvant cytotoxic liver perfusion for colorectal cancer. Br J Surg 1979;66:833–7.

    PubMed  CAS  Google Scholar 

  72. Taylor I, Machin D, Mullee M, Trotter G, Cooke T, West C. A randomized controlled trial of adjuvant portal vein cytotoxic perfusion in colorectal cancer. Br J Surg 1985;72:359–63.

    PubMed  CAS  Google Scholar 

  73. Metzger U. Adjuvant portal infusion chemotherapy in colonic cancer. EORTC Symposium on Gastrointestinal Tract Cancer Update on Combined Modality Therapy. Heidelberg, West Germany, May 29–30, 1986.

  74. Metzger U. Prevention of liver metastasis of colorectal carcinoma. In: Herfarth Ch, Schlag P, Hohenberger P, eds. Recent results in cancer research: therapeutic strategies in primary and metastatic liver cancer. New York: Springer-Verlag, 1986:29–34.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. EORTC GI Group, Brussels, Belgium

    M. Lise M.D., A. Gerard M.D., D. Nitti M.D., D. Zane M.D., M. Buyse, N. Duez, J. P. Arnaud M.D. & U. Metzger M.D.

Authors
  1. M. Lise M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. Gerard M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D. Nitti M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. D. Zane M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. Buyse
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. N. Duez
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. J. P. Arnaud M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. U. Metzger M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

European Organization for Research and Treatment of Cancer. Read at the International Cancer Congress, Budapest, Hungary, August 1986.

About this article

Cite this article

Lise, M., Gerard, A., Nitti, D. et al. Adjuvant therapy for colorectal cancer. Dis Colon Rectum 30, 847–854 (1987). https://doi.org/10.1007/BF02555422

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02555422

Key words

Search

Navigation