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Published in:

01-05-2010

Evolving Treatment of Advanced Colorectal Cancer

Authors: Andrea Cercek, Leonard Saltz

Published in: Current Oncology Reports | Issue 3/2010

Abstract

Advances in colorectal cancer treatment have led to improved outcomes for patients. A number of cytotoxic agents, alone and in combination, have shown activity. The addition of the newer, so-called “targeted” agents to standard chemotherapy drugs and regimens has also modestly improved outcomes. Progress in our knowledge and understanding of molecular pathways has led to the identification of markers critical in determining response or nonresponse to some of the targeted agents. This review discusses the available therapies in metastatic colorectal cancer and describes some of the molecular markers implicated in activity and resistance to current targeted therapies.

Tournigand C, Andre 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, 22:229–237.CrossRefPubMed

Colucci G, Gebbia V, Paoletti G, 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, 23:4866–4875.CrossRefPubMed

Diaz-Rubio E, Tabernero J, Gomez-Espana A, et al.: Phase III study of capecitabine plus oxaliplatin compared with continuous-infusion fluorouracil plus oxaliplatin as first-line therapy in metastatic colorectal cancer: final report of the Spanish Cooperative Group for the Treatment of Digestive Tumors Trial. J Clin Oncol 2007, 25:4224–4230.CrossRefPubMed

Porschen R, Arkenau HT, Kubicka S, et al.: Phase III study of capecitabine plus oxaliplatin compared with fluorouracil and leucovorin plus oxaliplatin in metastatic colorectal cancer: a final report of the AIO Colorectal Study Group. J Clin Oncol 2007, 25:4217–4223.CrossRefPubMed

Cassidy J, Clarke S, Diaz-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, 26:2006–2012.CrossRefPubMed

Kohne CH, De Greve J, Hartmann JT, et al.: Irinotecan combined with infusional 5-fluorouracil/folinic acid or capecitabine plus celecoxib or placebo in the first-line treatment of patients with metastatic colorectal cancer. EORTC study 40015. Ann Oncol 2008, 19:920–926.CrossRefPubMed

Fuchs CS, Marshall J, Mitchell E, et al.: Randomized, controlled trial of irinotecan plus infusional, bolus, or oral fluoropyrimidines in first-line treatment of metastatic colorectal cancer: results from the BICC-C Study. J Clin Oncol 2007, 25:4779–4786.CrossRefPubMed

Seymour MT, Maughan TS, Ledermann JA, et al.: Different strategies of sequential and combination chemotherapy for patients with poor prognosis advanced colorectal cancer (MRC FOCUS): a randomised controlled trial. Lancet 2007, 370:143–152.CrossRefPubMed

Koopman M, Antonini NF, Douma J, et al.: Sequential versus combination chemotherapy with capecitabine, irinotecan, and oxaliplatin in advanced colorectal cancer (CAIRO): a phase III randomised controlled trial. Lancet 2007, 370:135–142.CrossRefPubMed

10.

Tournigand C, Cervantes A, Figer A, et al.: OPTIMOX1: a randomized study of FOLFOX4 or FOLFOX7 with oxaliplatin in a stop-and-go fashion in advanced colorectal cancer—a GERCOR study. J Clin Oncol 2006, 24:394–400.CrossRefPubMed

11.

Chibaudel B, Maindrault-Goebel F, Lledo G, et al.: Can chemotherapy be discontinued in unresectable metastatic colorectal cancer? The GERCOR OPTIMOX2 Study. J Clin Oncol 2009, 27:5727–5733.CrossRefPubMed

12.

Hurwitz H, Fehrenbacher L, Novotny W, et al.: Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 2004, 350:2335–2342.CrossRefPubMed

13.

• Saltz LB, Clarke S, Diaz-Rubio E, et al.: Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol 2008, 26:2013–2019. The addition of bevacizumab to oxaliplatin-based chemotherapy improves PFS in first-line treatment of metastatic CRC. The response rate was not improved by the addition of bevacizumab, and the overall survival difference did not reach statistical significance.CrossRefPubMed

14.

Saltz LB, Rosen LS, Marshall JL, et al.: Phase II trial of sunitinib in patients with metastatic colorectal cancer after failure of standard therapy. J Clin Oncol 2007, 25:4793–4799.CrossRefPubMed

15.

Baselga J, Albanell J: Epithelial growth factor receptor interacting agents. Hematol Oncol Clin North Am 2002, 16:1041–1063.CrossRefPubMed

16.

Baselga J: Why the epidermal growth factor receptor? The rationale for cancer therapy. Oncologist 2002, 7(Suppl 4):2–8.CrossRefPubMed

17.

Salomon DS, Brandt R, Ciardiello F, et al.: Epidermal growth factor-related peptides and their receptors in human malignancies. Crit Rev Oncol Hematol 1995, 19:183–232.CrossRefPubMed

18.

Saltz LB, Rubin M, Hochester H, et al.: Cetuximab (IMC-C225) plus irinotecan (CPT-11) is active in CPT-11 refractory colorectal cancer (CRC) that expresses epiderman graowth factor receptor (EGFR). Proc Am Soc Clin Oncol 2001, 20:3a (Abstract 7)

19.

Saltz LB, Meropol NJ, Loeher PJ, et al.: Single agent IMC-C225 (ErbituxTM) has activity in CPT-11 refractory colorectal cancer (CRC) that expresses epidermal growth factor receptor (EGFR). Proc Am Soc Clin Oncol 2002; 21:(Abstract 504).

20.

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, 351:337–345.CrossRefPubMed

21.

Camp ER, Summy J, Bauer TW, et al.: Molecular mechanisms of resistance to therapies targeting the epidermal growth factor receptor. Clin Cancer Res 2005, 11:397–405.PubMed

22.

Hecht JR, Patnaik A, Malik I, et al.: ABX-EGF monotherapy in patients (pts) with metastatic colorectal cancer (mCRC): an updated analysis. Proc Am Soc Clin Oncol 2004, 22:248 (Abstract 3511)

23.

Berlin J, Neubauer M, Swanson P, et al.: Panitumumab antitumor activity in patients (pts) with metastatic colorectal cancer (mCRC) expressing ≥10% epidermal growth factor receptor (EGFR). J Clin Oncol 2006, 24(18 suppl):158s (Abstract 3548)

24.

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.CrossRefPubMed

25.

Van Cutsem E NM, Lang I, Cascinu S, et al.: Randomized phase III study of irinotecan and 5-FU/FA with or wihtout cetuximab in the first-line treatment of patients with metastatic colorectal cancer (mCRC): The CRYSTAL trial. J Clin Oncol 2007, 18(Suppl):4000.

26.

Bokemeyer C BI, Makhson A, Hartmann T, et al.: Cetuximab plus 5-FU/FA/oxaliplatin (FOLFOX-4) versus FOLFOX-4 in the first-line treatment of metastatic colrectal cancer (mCRC): OPUS, a randomized phase II study. J Clin Oncol 2007, 18(Suppl):4035.

27.

Tonra JR, Deevi DS, Corcoran E, et al.: Synergistic antitumor effects of combined epidermal growth factor receptor and vascular endothelial growth factor receptor-2 targeted therapy. Clin Cancer Res 2006, 12:2197–2207.CrossRefPubMed

28.

Saltz LB, Lenz HJ, Kindler HL, et al.: Randomized phase II trial of cetuximab, bevacizumab, and irinotecan compared with cetuximab and bevacizumab alone in irinotecan-refractory colorectal cancer: the BOND-2 study. J Clin Oncol 2007, 25:4557–4561.CrossRefPubMed

29.

Hecht JR ME, Chidiac T, Scroggin C, et al.: An updated analysis of saftey and efficacy of oxaliplatin (Ox)/bevacizumab (bev) +/− panitumumab (pmab) for first-line treatment (tx) of metastatic colorectal cancer (mCRC) from a randomized, controlled trial (PACCE). 2008 Gastrointestinal Cancers Symposium. Orlando, FL; January 25–27, 2008.

30.

Punt CJ, Tol J, Rodenburg CJ, et al.: Randomized phase III study of capecitabine, oxaliplatin, and bevacizumab with or without cetuximab in advanced colorectal cancer (ACC), the CAIRO2 study of the Dutch Colorectal Cancer Group (DCCG). J Clin Oncol 2008, 26(15 suppl):18-s (Abstract LBA 4011).

31.

Khambata-Ford S, Garrett CR, Meropol NJ, et al.: Expression of epiregulin and amphiregulin and K-ras mutation status predict disease control in metastatic colorectal cancer patients treated with cetuximab. J Clin Oncol 2007, 25:3230–3237.CrossRefPubMed

32.

Lievre A, Bachet JB, Boige V, et al.: KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab. J Clin Oncol 2008, 26:374–379.CrossRefPubMed

33.

• Amado RG, Wolf M, Peeters M, et al.: Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol 2008, 26:1626–1634. Wild-type KRAS is required for response to panitumumab. CrossRefPubMed

34.

Van Cutsem E, Lang I, D’haens G, et al.: KRAS status and efficacy in the first-line treatment of patients with metastatic colorectal cancer (mCRC) treated with FOLFIRI with or without cetuximab: the CRYSTAL experience. J Clin Oncol 2008, 26(15 suppl):5s (Abstract 2).

35.

Bokemeyer C, Bondarenko I, Makhson A, et al.: Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer. J Clin Oncol 2009, 27:663–671.CrossRefPubMed

36.

• 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, 26:5705–5712. Wild-type BRAF is required for response to panitumumab or cetuximab. Mutated BRAF appears to incur a worse prognosis.CrossRefPubMed

37.

Sartore-Bianchi A, Martini M, Molinari F, et al.: PIK3CA mutations in colorectal cancer are associated with clinical resistance to EGFR-targeted monoclonal antibodies. Cancer Res 2009, 69:1851–1857.CrossRefPubMed

Title: Evolving Treatment of Advanced Colorectal Cancer
Authors: Andrea Cercek
Leonard Saltz
Publication date: 01-05-2010
Publisher: Current Science Inc.
Published in: Current Oncology Reports / Issue 3/2010
Print ISSN: 1523-3790
Electronic ISSN: 1534-6269
DOI: https://doi.org/10.1007/s11912-010-0096-1

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