Cancer Chemotherapy and Pharmacology

, Volume 54, Supplement 1, pp S4–S11 | Cite as

Clinical overview: adjuvant therapy of gastrointestinal cancer

Article

Abstract

Adjuvant therapy has been tested widely in the treatment of cancers of the stomach, pancreas, and large bowel. In the USA, the use of postoperative chemoradiation in stomach cancer is considered a standard of care after the publication of the Intergroup Study 0116 in September 2001. This study demonstrated significant benefit in overall and disease-free survival for patients receiving postoperative treatment with fluorouracil (5-FU)/leucovorin chemotherapy and radiation after gastric resection. Adjuvant chemotherapy is not considered to be of significant benefit, and such therapy for patients with resected gastric cancer is investigational. There is interest in the use of neoadjuvant chemotherapy strategies as preoperative treatment followed by surgical resection. This approach has been tested in a randomized study of over 500 patients carried out by the Medical Research Council in the UK. This study demonstrated that patients receiving preoperative and postoperative epirubicin, cisplatin, 5-FU (ECF) chemotherapy, had a downstaging of tumor size, an increase in rates of curative resection, and an increase in disease-free but not overall survival. With pancreatic cancer, there is a controversy over postoperative chemoradiation after pancreatic resection. A recently completed Intergroup Study compared gemcitabine to 5-FU chemotherapy given before and after radiation in resected pancreatic cancer. Over 500 patients have been accrued to this study, which recently closed. In Western Europe, the results of a large clinical trial (ESPAC) have suggested that chemoradiation is not beneficial in patients with resected pancreatic cancer. In large bowel cancer, 5-FU-based adjuvant chemotherapy regimens are superior to surgery alone, particularly in node-positive patients. The use of newer combinations including 5-FU/leucovorin plus irinotecan and 5-FU/leucovorin plus oxaliplatin are also of interest as chemotherapy in resected colon cancer patients. The recent publication of the MOSAIC trial demonstrated that 5-FU/leucovorin/oxaliplatin (FOLFOX 4) improves progression-free survival in node-positive patients over 5-FU/leucovorin alone. The results of studies of 5-FU/leucovorin and irinotecan both in Europe (PETACC) and the USA (IFL vs 5-FU/leucovorin) are awaited with interest. Another area of interest in resected colon cancer is the use of molecular genetic monitoring to assess the likelihood of patient relapse. The data over the past several years have demonstrated that patients whose tumors do not have deletion of the deleted in colon cancer (DCC) gene on chromosome 18 have an improved outcome. Recent data are available with tumors that demonstrate microsatellite instability (MSI). Such tumors represent about 15% of all colon cancers and have an improved outcome when compared to those not expressing MSI, and may not benefit from adjuvant chemotherapy.

Keywords

Gastric Colonic Pancreatic Adjuvant chemotherapy 

References

  1. 1.
    Abrams RA, Lillemoe KD, Piantadosi S (2001) Continuing controversy over adjuvant therapy of pancreatic cancer. Lancet 358:929CrossRefGoogle Scholar
  2. 2.
    Allum W, Cunningham D, Weeden S, for the UK NCRI Upper GI Clinical Studies Group (2003) Perioperative chemotherapy in operable gastric and lower oesophageal cancer: a randomized, controlled trial (the MAGIC trial, ISRCTN 93793971) (abstract 998). Proc Am Soc Clin Oncol 22:249aGoogle Scholar
  3. 3.
    Anido J, Albanell J, Rojo F (2001) Inhibition by ZD1839 (Iressa) of epidermal growth factor and heregulin induced signaling pathways in human breast cancer cells (abstract 1712). Proc Am Soc Clin Oncol 20:429aGoogle Scholar
  4. 4.
    Atiq OT, Kelsen DP, Shiu MH (1993) Phase II trial of postoperative adjuvant intraperitoneal cisplatin and fluorouracil and systemic fluorouracil chemotherapy in patients with resected gastric cancer. J Clin Oncol 11:425PubMedGoogle Scholar
  5. 5.
    Bonenkamp JJ, Hermans J, Sasako M (1999) Extended lymph node dissection for gastric cancer. N Engl J Med 340:908CrossRefPubMedGoogle Scholar
  6. 6.
    Bunt AMG, Hermans J, Smit VT (1995) Surgical/pathologic-stage migration confounds comparisons of gastric cancer survival rates between Japan and Western countries. J Clin Oncol 13:19PubMedGoogle Scholar
  7. 7.
    Crookes P, Leichman CG, Leichman L, Tan M, Laine L, Stain S, Baranda J, Casagrande Y, Groshen S, Silberman H (1997) Systemic chemotherapy for gastric carcinoma followed by postoperative intraperitoneal therapy. Cancer 79:1767CrossRefPubMedGoogle Scholar
  8. 8.
    DeGramont A, Banzi M, Navarro M, Tabernero J, Hickish T, Bridgewater J, Rivera F, Figer A, Fountzilas G, Andre T (2003) Oxaliplatin/5-FU/LV in adjuvant colon cancer: results of the international randomized MOSAIC trial (abstract 1015). Proc Am Soc Clin Oncol 22:253aGoogle Scholar
  9. 9.
    Earle CC, Maroun JA (1999) Adjuvant chemotherapy after curative resection for gastric cancer in non-Asian patients: revisiting a meta-analysis of randomized trials. Eur J Cancer 35:1059CrossRefPubMedGoogle Scholar
  10. 10.
    Gastrointestinal Tumor Study Group (1982) A comparison of combination chemotherapy and combined modality therapy for locally advanced gastric carcinoma. Cancer 49:1771PubMedGoogle Scholar
  11. 11.
    Gastrointestinal Tumor Study Group (1987) Further evidence of effective adjuvant combined radiation and chemotherapy following curative resection of pancreatic cancer. Cancer 59:2006PubMedGoogle Scholar
  12. 12.
    Hermans J, Bonenkamp JJ, Boon MC, Bunt AM, Ohyama S, Sasako M, Van de Velde CJ (1993) Adjuvant therapy after curative resection for gastric cancer: meta-analysis of randomized trials. J Clin Oncol 11:1441PubMedGoogle Scholar
  13. 13.
    Herskovic A, Martz K, Al-Sarraf M, Leichman L, Brindle J, Vaitkevicius V, Cooper J, Byhardt R, Davis L, Emami B (1992) Combined chemotherapy and radiotherapy compared to radiotherapy alone in patients with cancer of the esophagus. N Engl J Med 326:1593PubMedGoogle Scholar
  14. 14.
    Jemal A, Murray T, Samuels A, Ghafoor A, Ward E, Thun MJ (2003) Cancer statistics, 2003. Cancer J Clin 53:5PubMedGoogle Scholar
  15. 15.
    Jen J, Kim H, Piantadosi S, Liu ZF, Levitt RC, Sistonen P, Kinzler KW, Vogelstein B, Hamilton SR (1994) Allelic loss of chromosome 18q and prognosis in colorectal cancer. N Engl J Med 331:213CrossRefPubMedGoogle Scholar
  16. 16.
    Kalser MH, Ellenberg SS (1985) Pancreatic cancer. Adjuvant combined radiation and chemotherapy following curative resection. Arch Surg 120:899PubMedGoogle Scholar
  17. 17.
    Kodama Y, Sugimachi K, Soejima K, Matsusaka T, Inokuchi K (1981) Evaluation of extensive lymph node dissection for carcinoma of the stomach. World J Surg 5:241PubMedGoogle Scholar
  18. 18.
    Macdonald JS, Astrow AB (2001) Adjuvant therapy of colon cancer. Semin Oncol 28:30CrossRefGoogle Scholar
  19. 19.
    Macdonald JS, Fleming TR, Peterson RF, Berenberg JL, McClure S, Chapman RA, Eyre HJ, Solanki D, Cruz AB Jr, Gagliano R, Estes NC, Tangen CM, Rivkin S (1995) Adjuvant chemotherapy with 5-FU, adriamycin, and mitomycin-C (FAM) versus surgery alone for patients with locally advanced gastric adenocarcinoma: a Southwest Oncology Group Study. Ann Surg Oncol 2:488PubMedGoogle Scholar
  20. 20.
    Macdonald JS, Smalley SR, Benedetti J, Hundahl SA, Estes NC, Stemmermann GN, Haller DG, Ajani JA, Gunderson LL, Jessup JM, Martenson JA (2001) Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med 345:725CrossRefPubMedGoogle Scholar
  21. 21.
    Neoptolemos JP, Dunn JA, Stocken DD, Almond J, Link K, Beger H, Bassi C, Falconi M, Pederzoli P, Dervenis C, Fernandez-Cruz L, Lacaine F, Pap A, Spooner D, Kerr DJ, Friess H, Buchler MW; European Study Group for Pancreatic Cancer (2001) Adjuvant chemoradiotherapy and chemotherapy in resectable pancreatic cancer: a randomised controlled trial. Lancet 358:1576CrossRefPubMedGoogle Scholar
  22. 22.
    Ribic CM, Sargent DJ, Moore MJ, Thibodeau SN, French AJ, Goldberg RM, Hamilton SR, Laurent-Puig P, Gryfe R, Shepherd LE, Tu D, Redston M, Gallinger S (2003) Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer. N Engl J Med 349:247CrossRefPubMedGoogle Scholar
  23. 23.
    Robertson CS, Chung SCS, Woods SDS, Griffin SM, Raimes SA, Lau JT, Li AK (1994) A prospective randomized trial comparing R1 subtotal gastrectomy with R3 total gastrectomy for antral cancer. Ann Surg 220:176PubMedGoogle Scholar
  24. 24.
    Ross P, Cunningham D, Scarffe H (1999) Results of a randomized trial comparing ECF with MCF in advanced oesophageal gastric cancer (abstract 1042). Proc Am Soc Clin Oncol 18:272aGoogle Scholar
  25. 25.
    Saltz L, Rubin M, Hochster H, Tchekmeydian NS, Waksal H, Needle M, LoBuglio A (2001) Cetuximab (IMC-C225) plus irinotecan (CPT-11) is active in CPT-11-refractory colorectal cancer that expresses epidermal growth factor receptor (abstract 7). Proc Am Soc Clin Oncol 20:3aGoogle Scholar
  26. 26.
    Vezerdis MP, Wanebo HJ (1992) Gastric cancer: surgical approach. In: Ahlgren JD, Macdonald JS (eds) Gastrointestinal oncology. J.B. Lippincott, Philadelphia, p 159Google Scholar
  27. 27.
    Watanabe T, Wu T-T, Catalano PJ, Ueki T, Satriano R, Haller DG, Benson AB 3rd, Hamilton SR (2001) Molecular predictors of survival after adjuvant chemotherapy for colon cancer. N Engl J Med 344:1196CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  1. 1.St. Vincent’s Comprehensive Cancer CenterNew YorkUSA

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