ABSTRACT
Colorectal cancer (CRC) is the third most common cancer and second leading cause of death from cancer in North America. The authors provide an overview of the indications for both chemotherapy and targeted therapy, as well as discuss the efficacy and toxicity of systemic therapy. They highlight the key studies that lead to the initial historical use of fluorouracil (5FU) based chemotherapy in the adjuvant and metastatic setting, the recent adoption of 5FU plus leucovorin (LV) and oxaliplatin (FOLFOX) chemotherapy over 5FU when treating adjuvant patients, and the use of FOLFOX or 5FU plus LV and irinotecan (FOLFIRI) in metastatic patients. They also review the role of chemotherapy in treating rectal cancer and resectable liver metastatic disease. Future areas of research focus for systemic therapy of colorectal cancer are highlighted.
KEYWORDS
Chemotherapy - adjuvant therapy - targeted therapy - metastatic
REFERENCES
-
1
Jemal A, Siegel R, Ward E et al..
Cancer statistics, 2008.
CA Cancer J Clin.
2008;
58(2)
71-96
-
2 Canadian Cancer Society/National Cancer Institute of Canada .Canadian Cancer Statistics. 2008 Toronto, Canada;
-
3
Therasse P, Arbuck S G, Eisenhauer E A et al..
New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada.
J Natl Cancer Inst.
2000;
92(3)
205-216
-
4
Wolmark N, Fisher B, Rockette H et al..
Postoperative adjuvant chemotherapy or BCG for colon cancer: results from NSABP protocol C-01.
J Natl Cancer Inst.
1988;
80(1)
30-36
-
5
Wolmark N, Rockette H, Fisher B et al..
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.
J Clin Oncol.
1993;
11(10)
1879-1887
-
6
Scheithauer W, Rosen H, Kornek G V, Sebesta C, Depisch D.
Randomised comparison of combination chemotherapy plus supportive care with supportive care alone in patients with metastatic colorectal cancer.
BMJ.
1993;
306(6880)
752-755
-
7 Jonker D S, Maroun K J. Adjuvant Systemic Chemotherapy for Stage II and III Colon Cancer Following Complete Resection: Guideline Recommendations. Cancer Care Ontario Evidence-Based Series#2–29 Toronto; Cancer Care Ontario 2008
-
8
André T, Boni C, Mounedji-Boudiaf L Multicenter International Study of Oxaliplatin/5-Fluorouracil/Leucovorin in the Adjuvant Treatment of Colon Cancer (MOSAIC) Investigators et al.
Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer.
N Engl J Med.
2004;
350(23)
2343-2351
-
9
De Gramont A, Boni C, Navarro M et al..
Oxaliplatin/5-FU/LV in adjuvant colon cancer: Updated efficacy results of the MOSAIC trial, including survival, with a median follow-up of six years.
Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings Part 1.
2007;
25(18S)
, Abstract 4007
-
10
Krueger G M, Alexander L L, Whippen D A, Balch C M.
Arnoldus Goudsmit, MD, PhD: chemotherapist, visionary, founder of the American Society of Clinical Oncology, 1909-2005.
J Clin Oncol.
2006;
24(24)
4033-4036
-
11
Tournigand C, André T, Achille E et al..
FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study.
J Clin Oncol.
2004;
22(2)
229-237
-
12
Colucci G, Gebbia V, Paoletti G Gruppo Oncologico Dell'Italia Meridionale et al.
Phase III randomized trial of FOLFIRI versus FOLFOX4 in the treatment of advanced colorectal cancer: a multicenter study of the Gruppo Oncologico Dell'Italia Meridionale.
J Clin Oncol.
2005;
23(22)
4866-4875
-
13
Hurwitz H, Fehrenbacher L, Novotny W et al..
Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer.
N Engl J Med.
2004;
350(23)
2335-2342
-
14 Saltz L, Clarke S, Diaz-Rubio E et al.. Bevacizumab (Bev) in combination with XELOX or FOLFOX4: efficacy results from XELOX-1/NO16966, a randomized phase III trial in the first-line treatment of metastatic colorectal cancer (MCRC). Paper presented at: Gastrointestinal Cancers Symposium, American Society of Clinical Oncologists July 19–21, 2007 Abstract 238 Orlando, FL;
-
15
Cassidy J, Clarke S, Díaz-Rubio E et al..
Randomized phase III study of capecitabine plus oxaliplatin compared with fluorouracil/folinic acid plus oxaliplatin as first-line therapy for metastatic colorectal cancer.
J Clin Oncol.
2008;
26(12)
2006-2012
-
16
Cunningham D, Humblet Y, Siena S et al..
Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer.
N Engl J Med.
2004;
351(4)
337-345
-
17
Jonker D J, O'Callaghan C J, Karapetis C S et al..
Cetuximab for the treatment of colorectal cancer.
N Engl J Med.
2007;
357(20)
2040-2048
-
18
Van Cutsem E, Köhne C H, Hitre E et al..
Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer.
N Engl J Med.
2009;
360(14)
1408-1417
-
19
Karapetis C S, Khambata-Ford S, Jonker D J et al..
K-ras mutations and benefit from cetuximab in advanced colorectal cancer.
N Engl J Med.
2008;
359(17)
1757-1765
-
20
Van Cutsem E, Peeters M, Siena S et al..
Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer.
J Clin Oncol.
2007;
25
1658-1664
-
21
Amado R G, Wolf M, Peeters M et al..
Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer.
J Clin Oncol.
2008;
26(10)
1626-1634
-
22
Nordlinger B, Sorbye H, Glimelius B EORTC Gastro-Intestinal Tract Cancer Group et al.
Perioperative chemotherapy with FOLFOX4 and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC Intergroup trial 40983): a randomised controlled trial.
Lancet.
2008;
371(9617)
1007-1016
-
23
Gastro-intestinal Tumor Study Group .
Prolongation of the disease-free interval in surgically treated rectal carcinoma.
N Engl J Med.
1985;
312
1465-1472
-
24
Krook J E, Moertel C G, Gunderson L L et al..
Effective surgical adjuvant therapy for high-risk rectal carcinoma.
N Engl J Med.
1991;
324(11)
709-715
-
25
Sauer R, Becker H, Hohenberger W German Rectal Cancer Study Group et al.
Preoperative versus postoperative chemoradiotherapy for rectal cancer.
N Engl J Med.
2004;
351(17)
1731-1740
-
26
Gérard J P, Conroy T, Bonnetain F et al..
Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3-4 rectal cancers: results of FFCD 9203.
J Clin Oncol.
2006;
24(28)
4620-4625
-
27
Gryfe R, Kim H, Hsieh E T et al..
Tumor microsatellite instability and clinical outcome in young patients with colorectal cancer.
N Engl J Med.
2000;
342(2)
69-77
-
28
Hemminki A, Mecklin J P, Järvinen H, Aaltonen L A, Joensuu H.
Microsatellite instability is a favorable prognostic indicator in patients with colorectal cancer receiving chemotherapy.
Gastroenterology.
2000;
119(4)
921-928
-
29
Ribic C M, Sargent D J, Moore M J et al..
Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer.
N Engl J Med.
2003;
349(3)
247-257
-
30
Jonker D J, Karpetis C, Harbison C et al..
High epiregulin (EREG) gene expression plus K-ras wild-type (WT) status as predictors of cetuximab benefit in the treatment of advanced colorectal cancer (ACRC): results from NCIC CTG CO.17- A phase III trial of cetuximab versus best supportive care (BSC).
J Clin Oncol.
2009;
27(15S)
, Abstract 4016
-
31
Loupakis F, Pollina L, Stasi I et al..
PTEN expression and KRAS mutations on primary tumors and metastases in the prediction of benefit from cetuximab plus irinotecan for patients with metastatic colorectal cancer.
J Clin Oncol.
2009;
27(16)
2622-2629
-
32
Di Nicolantonio F, Martini M, Molinari F et al..
Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer.
J Clin Oncol.
2008;
26(35)
5705-5712
Timothy R AsmisM.D.
The Ottawa Hospital Regional Cancer Centre
501 Smyth Rd., Box 913, Ottawa, Ontario, Canada K1H 8L6
eMail: tasmis@ottawahospital.on.ca
