Skip to main content
SpringerLink
Log in

Metastatic Rectal Cancer

  • Chapter
  • First Online:
Modern Management of Cancer of the Rectum

  • 1457 Accesses

Abstract

Colorectal cancer is a common malignancy and up to 20 % of patients have metastases at diagnosis and up to 50 % of those with localized disease will suffer a recurrence. The problem of metastatic colorectal cancer is therefore substantial. Most patients with metastatic colorectal cancer are treated with palliative intent where the treatment is aimed at prolonging survival and maintaining the quality of life of patients for as long as possible. There have been major advances in the management of metastatic colorectal cancer in the last decade with the advent of multiple new agents for systemic therapy, both cytotoxic drugs and biological agents such as VEGF and EGFR inhibitors. As a result, the overall survival of patients with metastatic colorectal cancer has improved markedly. Furthermore, biomarkers are assuming a larger role in the management of and allow for more tailored management of individual patients.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 179.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Siegel R, Ma J, Zou Z, et al. Cancer statistics, 2014. CA Cancer J Clin. 2014;64:9–29.

    Article  PubMed  Google Scholar 

  2. SEER stat fact sheets: colorectal cancer. http://seer.cancer.gov/statfacts/html/colorect.html.

  3. Venook AP, Niedzwiecki D, Lenz H, et al. CALGB/SWOG 80405: phase III trial of irinotecan/5-FU/leucovorin (FOLFIRI) or oxaliplatin/5-FU/leucovorin (mFOLFOX6) with bevacizumab (BV) or cetuximab (CET) for patients (pts) with KRAS wild-type (wt) untreated metastatic adenocarcinoma of the colon or rectum (MCRC). J Clin Oncol. 2014;32:5s (Suppl; abstr LBA3).

    Article  CAS  Google Scholar 

  4. Scheithauer W, Rosen H, Kornek GV, et al. Randomised comparison of combination chemotherapy plus supportive care with supportive care alone in patients with metastatic colorectal cancer. BMJ. 1993;306:752–5.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Simmonds PC. Palliative chemotherapy for advanced colorectal cancer: systematic review and meta-analysis. Colorectal Cancer Collaborative Group. BMJ. 2000;321:531–5.

    Article  CAS  PubMed  Google Scholar 

  6. Grothey A, Sargent D. Overall survival of patients with advanced colorectal cancer correlates with availability of fluorouracil, irinotecan, and oxaliplatin regardless of whether doublet or single-agent therapy is used first line. J Clin Oncol. 2005;23:9441–2.

    Article  PubMed  Google Scholar 

  7. Grothey A, Sargent D, Goldberg RM, et al. Survival of patients with advanced colorectal cancer improves with the availability of fluorouracil-leucovorin, irinotecan, and oxaliplatin in the course of treatment. J Clin Oncol. 2004;22:1209–14.

    Article  CAS  PubMed  Google Scholar 

  8. Sanoff HK, Sargent DJ, Campbell ME, et al. Five-year data and prognostic factor analysis of oxaliplatin and irinotecan combinations for advanced colorectal cancer: N9741. J Clin Oncol. 2008;26:5721–7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Abrams TA, Meyer G, Schrag D, et al. Chemotherapy usage patterns in a US-wide cohort of patients with metastatic colorectal cancer. J Natl Cancer Inst. 2014;106:djt371.

    Article  PubMed  CAS  Google Scholar 

  10. Sorbye H, Pfeiffer P, Cavalli-Bjorkman N, et al. Clinical trial enrollment, patient characteristics, and survival differences in prospectively registered metastatic colorectal cancer patients. Cancer. 2009;115:4679–87.

    Article  PubMed  Google Scholar 

  11. Mol L, Koopman M, van Gils CW, et al. Comparison of treatment outcome in metastatic colorectal cancer patients included in a clinical trial versus daily practice in The Netherlands. Acta Oncol. 2013;52:950–5.

    Article  PubMed  Google Scholar 

  12. Van Cutsem E, Twelves C, Cassidy J, et al. Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: results of a large phase III study. J Clin Oncol. 2001;19:4097–106.

    PubMed  Google Scholar 

  13. Hoff PM, Ansari R, Batist G, et al. Comparison of oral capecitabine versus intravenous fluorouracil plus leucovorin as first-line treatment in 605 patients with metastatic colorectal cancer: results of a randomized phase III study. J Clin Oncol. 2001;19:2282–92.

    CAS  PubMed  Google Scholar 

  14. Arkenau HT, Arnold D, Cassidy J, et al. Efficacy of oxaliplatin plus capecitabine or infusional fluorouracil/leucovorin in patients with metastatic colorectal cancer: a pooled analysis of randomized trials. J Clin Oncol. 2008;26:5910–7.

    Article  CAS  PubMed  Google Scholar 

  15. 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;25:4217–23.

    Article  CAS  PubMed  Google Scholar 

  16. 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;26:2006–12.

    Article  CAS  PubMed  Google Scholar 

  17. Ducreux M, Bennouna J, Hebbar M, et al. Capecitabine plus oxaliplatin (XELOX) versus 5-fluorouracil/leucovorin plus oxaliplatin (FOLFOX-6) as first-line treatment for metastatic colorectal cancer. Int J Cancer. 2011;128:682–90.

    Article  CAS  PubMed  Google Scholar 

  18. 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;25:4224–30.

    Article  CAS  PubMed  Google Scholar 

  19. Hu ZY, Yu Q, Pei Q, et al. Dose-dependent association between UGT1A1*28 genotype and irinotecan-induced neutropenia: low doses also increase risk. Clin Cancer Res. 2010;16:3832–42.

    Article  CAS  PubMed  Google Scholar 

  20. McLeod HL, Sargent DJ, Marsh S, et al. Pharmacogenetic predictors of adverse events and response to chemotherapy in metastatic colorectal cancer: results from North American Gastrointestinal Intergroup Trial N9741. J Clin Oncol. 2010;28:3227–33.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Cunningham D, Pyrhonen S, James RD, et al. Randomised trial of irinotecan plus supportive care versus supportive care alone after fluorouracil failure for patients with metastatic colorectal cancer. Lancet. 1998;352:1413–8.

    Article  CAS  PubMed  Google Scholar 

  22. Rougier P, Van Cutsem E, Bajetta E, et al. Randomised trial of irinotecan versus fluorouracil by continuous infusion after fluorouracil failure in patients with metastatic colorectal cancer. Lancet. 1998;352:1407–12.

    Article  CAS  PubMed  Google Scholar 

  23. Strickler JH, Hurwitz HI. Bevacizumab-based therapies in the first-line treatment of metastatic colorectal cancer. Oncologist. 2012;17:513–24.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Ellis LM. Mechanisms of action of bevacizumab as a component of therapy for metastatic colorectal cancer. Semin Oncol. 2006;33:S1–7.

    Article  CAS  PubMed  Google Scholar 

  25. Geiger-Gritsch S, Stollenwerk B, Miksad R, et al. Safety of bevacizumab in patients with advanced cancer: a meta-analysis of randomized controlled trials. Oncologist. 2010;15:1179–91.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Abu-Hejleh T, Mezhir JJ, Goodheart MJ, et al. Incidence and management of gastrointestinal perforation from bevacizumab in advanced cancers. Curr Oncol Rep. 2012;14:277–84.

    Article  CAS  PubMed  Google Scholar 

  27. Keefe D, Bowen J, Gibson R, et al. Noncardiac vascular toxicities of vascular endothelial growth factor inhibitors in advanced cancer: a review. Oncologist. 2011;16:432–44.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Scappaticci FA, Skillings JR, Holden SN, et al. Arterial thromboembolic events in patients with metastatic carcinoma treated with chemotherapy and bevacizumab. J Natl Cancer Inst. 2007;99:1232–9.

    Article  PubMed  Google Scholar 

  29. Dietvorst MH, Eskens FA. Current and novel treatment options for metastatic colorectal cancer: emphasis on aflibercept. Biol Ther. 2013;3:25–33.

    Article  PubMed Central  PubMed  Google Scholar 

  30. Gaya A, Tse V. A preclinical and clinical review of aflibercept for the management of cancer. Cancer Treat Rev. 2012;38:484–93.

    Article  CAS  PubMed  Google Scholar 

  31. Van Cutsem E, Tabernero J, Lakomy R, et al. Addition of aflibercept to fluorouracil, leucovorin, and irinotecan improves survival in a phase III randomized trial in patients with metastatic colorectal cancer previously treated with an oxaliplatin-based regimen. J Clin Oncol. 2012;30:3499–506.

    Article  PubMed  CAS  Google Scholar 

  32. Aprile G, Macerelli M, Giuliani F. Regorafenib for gastrointestinal malignancies: from preclinical data to clinical results of a novel multi-target inhibitor. BioDrugs. 2013;27:213–24.

    Article  CAS  PubMed  Google Scholar 

  33. Grothey A, Van Cutsem E, Sobrero A, et al. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2013;381:303–12.

    Article  CAS  PubMed  Google Scholar 

  34. Vincenzi B, Zoccoli A, Pantano F, et al. Cetuximab: from bench to bedside. Curr Cancer Drug Targets. 2010;10:80–95.

    Article  CAS  PubMed  Google Scholar 

  35. Douillard JY, Oliner KS, Siena S, et al. Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer. N Engl J Med. 2013;369:1023–34.

    Article  CAS  PubMed  Google Scholar 

  36. Van Cutsem E, Kohne CH, Hitre E, et al. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med. 2009;360:1408–17.

    Article  PubMed  Google Scholar 

  37. Dahabreh IJ, Terasawa T, Castaldi PJ, et al. Systematic review: anti-epidermal growth factor receptor treatment effect modification by KRAS mutations in advanced colorectal cancer. Ann Intern Med. 2011;154:37–49.

    Article  PubMed  Google Scholar 

  38. Allegra CJ, Jessup JM, Somerfield MR, et al. American Society of Clinical Oncology provisional clinical opinion: testing for KRAS gene mutations in patients with metastatic colorectal carcinoma to predict response to anti-epidermal growth factor receptor monoclonal antibody therapy. J Clin Oncol. 2009;27:2091–6.

    Article  PubMed  Google Scholar 

  39. Peeters M, Oliner KS, Price TJ, et al. Analysis of KRAS/NRAS mutations in phase 3 study 20050181 of panitumumab (pmab) plus FOLFIRI versus FOLFIRI for second-line treatment (tx) of metastatic colorectal cancer (mCRC). J Clin Oncol. 2014;32(Suppl 3): Abstract LBA387.

    Google Scholar 

  40. Lochhead P, Kuchiba A, Imamura Y, et al. Microsatellite instability and BRAF mutation testing in colorectal cancer prognostication. J Natl Cancer Inst. 2013;105:1151–6.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  41. Safaee Ardekani G, Jafarnejad SM, Tan L, et al. The prognostic value of BRAF mutation in colorectal cancer and melanoma: a systematic review and meta-analysis. PLoS One. 2012;7:e47054.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  42. Goldberg RM, Rothenberg ML, Van Cutsem E, et al. The continuum of care: a paradigm for the management of metastatic colorectal cancer. Oncologist. 2007;12:38–50.

    Article  PubMed  Google Scholar 

  43. de Gramont A, Bosset JF, Milan C, et al. Randomized trial comparing monthly low-dose leucovorin and fluorouracil bolus with bimonthly high-dose leucovorin and fluorouracil bolus plus continuous infusion for advanced colorectal cancer: a French intergroup study. J Clin Oncol. 1997;15:808–15.

    PubMed  Google Scholar 

  44. Saltz LB, Cox JV, Blanke C, et al. Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer. Irinotecan Study Group. N Engl J Med. 2000;343:905–14.

    Article  CAS  PubMed  Google Scholar 

  45. Douillard JY, Cunningham D, Roth AD, et al. Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial. Lancet. 2000;355:1041–7.

    Article  CAS  PubMed  Google Scholar 

  46. Kohne CH, van Cutsem E, Wils J, et al. Phase III study of weekly high-dose infusional fluorouracil plus folinic acid with or without irinotecan in patients with metastatic colorectal cancer: European Organisation for Research and Treatment of Cancer Gastrointestinal Group Study 40986. J Clin Oncol. 2005;23:4856–65.

    Article  PubMed  CAS  Google Scholar 

  47. de Gramont A, Figer A, Seymour M, et al. Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol. 2000;18:2938–47.

    PubMed  Google Scholar 

  48. Goldberg RM, Sargent DJ, Morton RF, et al. A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer. J Clin Oncol. 2004;22:23–30.

    Article  CAS  PubMed  Google Scholar 

  49. 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;22:229–37.

    Article  CAS  PubMed  Google Scholar 

  50. 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;23:4866–75.

    Article  CAS  PubMed  Google Scholar 

  51. Falcone A, Ricci S, Brunetti I, et al. Phase III trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) compared with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatment for metastatic colorectal cancer: the Gruppo Oncologico Nord Ovest. J Clin Oncol. 2007;25:1670–6.

    Article  CAS  PubMed  Google Scholar 

  52. Souglakos J, Androulakis N, Syrigos K, et al. FOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin and irinotecan) vs FOLFIRI (folinic acid, 5-fluorouracil and irinotecan) as first-line treatment in metastatic colorectal cancer (MCC): a multicentre randomised phase III trial from the Hellenic Oncology Research Group (HORG). Br J Cancer. 2006;94:798–805.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  53. 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;370:135–42.

    Article  CAS  PubMed  Google Scholar 

  54. 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;370:143–52.

    Article  CAS  PubMed  Google Scholar 

  55. Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982;5:649–55.

    Article  CAS  PubMed  Google Scholar 

  56. Schag CC, Heinrich RL, Ganz PA. Karnofsky performance status revisited: reliability, validity, and guidelines. J Clin Oncol. 1984;2:187–93.

    CAS  PubMed  Google Scholar 

  57. Guo Y, Shi M, Shen X, et al. Capecitabine plus irinotecan versus 5-FU/leucovorin plus irinotecan in the treatment of colorectal cancer: a meta-analysis. Clin Colorectal Cancer. 2014;13:110–8.

    Article  PubMed  Google Scholar 

  58. Masi G, Vasile E, Loupakis F, et al. Randomized trial of two induction chemotherapy regimens in metastatic colorectal cancer: an updated analysis. J Natl Cancer Inst. 2011;103:21–30.

    Article  PubMed  Google Scholar 

  59. Falcone A, Cremolini C, Masi G, et al. FOLFOXIRI/bevacizumab (bev) versus FOLFIRI/bev as first-line treatment in unresectable metastatic colorectal cancer (mCRC) patients (pts): results of the phase III TRIBE trial by GONO group. J Clin Oncol. 2013;31(Suppl):Abstract 3505.

    Google Scholar 

  60. Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004;350:2335–42.

    Article  CAS  PubMed  Google Scholar 

  61. 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;26:2013–9.

    Article  CAS  PubMed  Google Scholar 

  62. 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;25:4779–86.

    Article  CAS  PubMed  Google Scholar 

  63. Kabbinavar FF, Hambleton J, Mass RD, et al. Combined analysis of efficacy: the addition of bevacizumab to fluorouracil/leucovorin improves survival for patients with metastatic colorectal cancer. J Clin Oncol. 2005;23:3706–12.

    Article  CAS  PubMed  Google Scholar 

  64. Tebbutt NC, Wilson K, Gebski VJ, et al. Capecitabine, bevacizumab, and mitomycin in first-line treatment of metastatic colorectal cancer: results of the Australasian Gastrointestinal Trials Group Randomized Phase III MAX Study. J Clin Oncol. 2010;28:3191–8.

    Article  CAS  PubMed  Google Scholar 

  65. Cunningham D, Lang I, Marcuello E, et al. Bevacizumab plus capecitabine versus capecitabine alone in elderly patients with previously untreated metastatic colorectal cancer (AVEX): an open-label, randomised phase 3 trial. Lancet Oncol. 2013;14:1077–85.

    Article  CAS  PubMed  Google Scholar 

  66. Maughan TS, Adams RA, Smith CG, et al. Addition of cetuximab to oxaliplatin-based first-line combination chemotherapy for treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trial. Lancet. 2011;377:2103–14.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  67. Tveit KM, Guren T, Glimelius B, et al. Phase III trial of cetuximab with continuous or intermittent fluorouracil, leucovorin, and oxaliplatin (Nordic FLOX) versus FLOX alone in first-line treatment of metastatic colorectal cancer: the NORDIC-VII study. J Clin Oncol. 2012;30:1755–62.

    Article  CAS  PubMed  Google Scholar 

  68. Bokemeyer C, Bondarenko I, Hartmann JT, et al. Efficacy according to biomarker status of cetuximab plus FOLFOX-4 as first-line treatment for metastatic colorectal cancer: the OPUS study. Ann Oncol. 2011;22:1535–46.

    Article  CAS  PubMed  Google Scholar 

  69. Douillard JY, Siena S, Cassidy J, et al. Final results from PRIME: randomized phase III study of panitumumab with FOLFOX4 for first-line treatment of metastatic colorectal cancer. Ann Oncol. 2014;25:1346–55.

    Article  CAS  PubMed  Google Scholar 

  70. Schwartzberg LS, Rivera F, Karthaus M, et al. PEAK: a randomized, multicenter phase II study of panitumumab plus modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or bevacizumab plus mFOLFOX6 in patients with previously untreated, unresectable, wild-type KRAS exon 2 metastatic colorectal cancer. J Clin Oncol. 2014;32:2240–7.

    Article  CAS  PubMed  Google Scholar 

  71. Hurwitz HI, Tebbutt NC, Kabbinavar F, et al. Efficacy and safety of bevacizumab in metastatic colorectal cancer: pooled analysis from seven randomized controlled trials. Oncologist. 2013;18:1004–12.

    Article  PubMed Central  PubMed  Google Scholar 

  72. Bennouna J, Sastre J, Arnold D, et al. Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): a randomised phase 3 trial. Lancet Oncol. 2013;14:29–37.

    Article  CAS  PubMed  Google Scholar 

  73. Grothey A, Sugrue MM, Purdie DM, et al. Bevacizumab beyond first progression is associated with prolonged overall survival in metastatic colorectal cancer: results from a large observational cohort study (BRiTE). J Clin Oncol. 2008;26:5326–34.

    Article  CAS  PubMed  Google Scholar 

  74. Cartwright TH, Yim YM, Yu E, et al. Survival outcomes of bevacizumab beyond progression in metastatic colorectal cancer patients treated in US community oncology. Clin Colorectal Cancer. 2012;11:238–46.

    Article  CAS  PubMed  Google Scholar 

  75. Grothey A, Flick ED, Cohn AL, et al. Bevacizumab exposure beyond first disease progression in patients with metastatic colorectal cancer: analyses of the ARIES observational cohort study. Pharmacoepidemiol Drug Saf. 2014;23:726–34.

    Article  CAS  PubMed  Google Scholar 

  76. Jonker DJ, O’Callaghan CJ, Karapetis CS, et al. Cetuximab for the treatment of colorectal cancer. N Engl J Med. 2007;357:2040–8.

    Article  CAS  PubMed  Google Scholar 

  77. Karapetis CS, Khambata-Ford S, Jonker DJ, et al. K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med. 2008;359:1757–65.

    Article  CAS  PubMed  Google Scholar 

  78. Van Cutsem E, Kohne CH, Lang I, et al. Cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumor KRAS and BRAF mutation status. J Clin Oncol. 2011;29:2011–9.

    Article  PubMed  CAS  Google Scholar 

  79. Vale CL, Tierney JF, Fisher D, et al. Does anti-EGFR therapy improve outcome in advanced colorectal cancer? A systematic review and meta-analysis. Cancer Treat Rev. 2012;38:618–25.

    Article  CAS  PubMed  Google Scholar 

  80. Loupakis F, Cremolini C, Salvatore L, et al. Clinical impact of anti-epidermal growth factor receptor monoclonal antibodies in first-line treatment of metastatic colorectal cancer: meta-analytical estimation and implications for therapeutic strategies. Cancer. 2012;118:1523–32.

    Article  CAS  PubMed  Google Scholar 

  81. Heinemann V, von Weikersthal LF, Decker T, et al. Randomized comparison of FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment of KRAS wild-type metastatic colorectal cancer: German AIO study KRK-0306 (FIRE-3). J Clin Oncol. 2013;31(Suppl):Abstract LBA3506.

    Google Scholar 

  82. Sridharan M, Hubbard JM, Grothey A. Colorectal cancer: how emerging molecular understanding affects treatment decisions. Oncology (Williston Park). 2014;28(2):110–8.

    Google Scholar 

  83. Au HJ, Karapetis CS, O’Callaghan CJ, et al. Health-related quality of life in patients with advanced colorectal cancer treated with cetuximab: overall and KRAS-specific results of the NCIC CTG and AGITG CO.17 Trial. J Clin Oncol. 2009;27:1822–8.

    Article  CAS  PubMed  Google Scholar 

  84. 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;26:1626–34.

    Article  CAS  PubMed  Google Scholar 

  85. 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;25:1658–64.

    Article  PubMed  CAS  Google Scholar 

  86. Van Cutsem E, Siena S, Humblet Y, et al. An open-label, single-arm study assessing safety and efficacy of panitumumab in patients with metastatic colorectal cancer refractory to standard chemotherapy. Ann Oncol. 2008;19:92–8.

    Article  PubMed  Google Scholar 

  87. Price TJ, Peeters M, Kim TW, et al. Panitumumab versus cetuximab in patients with chemotherapy-refractory wild-type KRAS exon 2 metastatic colorectal cancer (ASPECCT): a randomised, multicentre, open-label, non-inferiority phase 3 study. Lancet Oncol. 2014;15:569–79.

    Article  CAS  PubMed  Google Scholar 

  88. 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.

    Article  CAS  PubMed  Google Scholar 

  89. 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;27:5727–33.

    Article  CAS  PubMed  Google Scholar 

  90. Hochster HS, Grothey A, Hart L, et al. Improved time to treatment failure with an intermittent oxaliplatin strategy: results of CONcePT. Ann Oncol. 2014;25:1172–8.

    Article  CAS  PubMed  Google Scholar 

  91. Yalcin S, Uslu R, Dane F, et al. Bevacizumab + capecitabine as maintenance therapy after initial bevacizumab + XELOX treatment in previously untreated patients with metastatic colorectal cancer: phase III ‘Stop and Go’ study result-- Turkish Oncology Group Trial. Oncology. 2013;85:328–35.

    Google Scholar 

  92. Arnold A, Graeven U, Lerchenmuller CA, et al. Maintenance strategy with fluoropyrimidines (FP) plus Bevacizumab (Bev), Bev alone, or no treatment, following a standard combination of FP, oxaliplatin (Ox), and Bev as first-line treatment for patients with metastatic colorectal cancer (mCRC): a phase III non-inferiority trial (AIO KRK 0207). J Clin Oncol. 2014;32:5s (Suppl; abstr 3503).

    Article  CAS  Google Scholar 

  93. Koopman M, Simkens L, May AM, et al. Final results and subgroup analyses of the phase 3 CAIRO3 study: maintenance treatment with capecitabine + bevacizumab versus observation after induction treatment with chemotherapy + bevacizumab in metastatic colorectal cancer (mCRC). J Clin Oncol. 2014;32:5s (Suppl; abstr 3504).

    Article  CAS  Google Scholar 

  94. Papamichael D, Audisio RA, Glimelius B, et al. Treatment of colorectal cancer in older patients. International Society of Geriatric Oncology (SIOG) consensus recommendations 2013. Ann Oncol. 2014 Jul 11. pii: mdu253 [Epub ahead of print].

    Google Scholar 

  95. Pallis AG, Papamichael D, Audisio R, et al. EORTC Elderly Task Force experts’ opinion for the treatment of colon cancer in older patients. Cancer Treat Rev. 2010;36:83–90.

    Article  CAS  PubMed  Google Scholar 

  96. Sanoff HK, Goldberg RM. How we treat metastatic colon cancer in older adults. J Geriatr Oncol. 2013;4:295–301.

    Article  PubMed  Google Scholar 

  97. Folprecht G, Seymour MT, Saltz L, et al. Irinotecan/fluorouracil combination in first-line therapy of older and younger patients with metastatic colorectal cancer: combined analysis of 2,691 patients in randomized controlled trials. J Clin Oncol. 2008;26:1443–51.

    Article  CAS  PubMed  Google Scholar 

  98. Aparicio T, Desrame J, Lecomte T, et al. Oxaliplatin- or irinotecan-based chemotherapy for metastatic colorectal cancer in the elderly. Br J Cancer. 2003;89:1439–44.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  99. Goldberg RM, Tabah-Fisch I, Bleiberg H, et al. Pooled analysis of safety and efficacy of oxaliplatin plus fluorouracil/leucovorin administered bimonthly in elderly patients with colorectal cancer. J Clin Oncol. 2006;24:4085–91.

    Article  CAS  PubMed  Google Scholar 

  100. Folprecht G, Cunningham D, Ross P, et al. Efficacy of 5-fluorouracil-based chemotherapy in elderly patients with metastatic colorectal cancer: a pooled analysis of clinical trials. Ann Oncol. 2004;15:1330–8.

    Article  CAS  PubMed  Google Scholar 

  101. Sastre J, Aranda E, Massuti B, et al. Elderly patients with advanced colorectal cancer derive similar benefit without excessive toxicity after first-line chemotherapy with oxaliplatin-based combinations: comparative outcomes from the 03-TTD-01 phase III study. Crit Rev Oncol Hematol. 2009;70:134–44.

    Article  PubMed  Google Scholar 

  102. Meyerhardt JA, Li L, Sanoff HK, et al. Effectiveness of bevacizumab with first-line combination chemotherapy for Medicare patients with stage IV colorectal cancer. J Clin Oncol. 2012;30:608–15.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  103. Tsai HT, Marshall JL, Weiss SR, et al. Bevacizumab use and risk of cardiovascular adverse events among elderly patients with colorectal cancer receiving chemotherapy: a population-based study. Ann Oncol. 2013;24:1574–9.

    Article  PubMed Central  PubMed  Google Scholar 

  104. Jehn CF, Boning L, Kroning H, et al. Influence of comorbidity, age and performance status on treatment efficacy and safety of cetuximab plus irinotecan in irinotecan-refractory elderly patients with metastatic colorectal cancer. Eur J Cancer. 2014;50:1269–75.

    Article  CAS  PubMed  Google Scholar 

  105. Jehn CF, Boning L, Kroning H, et al. Cetuximab-based therapy in elderly comorbid patients with metastatic colorectal cancer. Br J Cancer. 2012;106:274–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  106. Seymour MT, Thompson LC, Wasan HS, et al. Chemotherapy options in elderly and frail patients with metastatic colorectal cancer (MRC FOCUS2): an open-label, randomised factorial trial. Lancet. 2011;377:1749–59.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  107. Sastre J, Gravalos C, Rivera F, et al. First-line cetuximab plus capecitabine in elderly patients with advanced colorectal cancer: clinical outcome and subgroup analysis according to KRAS status from a Spanish TTD Group Study. Oncologist. 2012;17:339–45.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  108. Halfdanarson TR, Jatoi A. Oral cancer chemotherapy: the critical interplay between patient education and patient safety. Curr Oncol Rep. 2010;12:247–52.

    Article  CAS  PubMed  Google Scholar 

  109. Sargent DJ, Kohne CH, Sanoff HK, et al. Pooled safety and efficacy analysis examining the effect of performance status on outcomes in nine first-line treatment trials using individual data from patients with metastatic colorectal cancer. J Clin Oncol. 2009;27:1948–55.

    Article  PubMed Central  PubMed  Google Scholar 

  110. Simmonds PC, Primrose JN, Colquitt JL, et al. Surgical resection of hepatic metastases from colorectal cancer: a systematic review of published studies. Br J Cancer. 2006;94:982–99.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  111. Morris EJ, Forman D, Thomas JD, et al. Surgical management and outcomes of colorectal cancer liver metastases. Br J Surg. 2010;97:1110–8.

    Article  CAS  PubMed  Google Scholar 

  112. Kopetz S, Chang GJ, Overman MJ, et al. Improved survival in metastatic colorectal cancer is associated with adoption of hepatic resection and improved chemotherapy. J Clin Oncol. 2009;27:3677–83.

    Article  PubMed Central  PubMed  Google Scholar 

  113. Halfdanarson TR, Kendrick ML, Grothey A. The role of chemotherapy in managing patients with resectable liver metastases. Cancer J. 2010;16:125–31.

    Article  CAS  PubMed  Google Scholar 

  114. Soubrane O, Brouquet A, Zalinski S, et al. Predicting high grade lesions of sinusoidal obstruction syndrome related to oxaliplatin-based chemotherapy for colorectal liver metastases: correlation with post-hepatectomy outcome. Ann Surg. 2010;251:454–60.

    Article  PubMed  Google Scholar 

  115. Karoui M, Penna C, Amin-Hashem M, et al. Influence of preoperative chemotherapy on the risk of major hepatectomy for colorectal liver metastases. Ann Surg. 2006;243:1–7.

    Article  PubMed Central  PubMed  Google Scholar 

  116. Vauthey JN, Pawlik TM, Ribero D, et al. Chemotherapy regimen predicts steatohepatitis and an increase in 90-day mortality after surgery for hepatic colorectal metastases. J Clin Oncol. 2006;24:2065–72.

    Article  CAS  PubMed  Google Scholar 

  117. Kooby DA, Fong Y, Suriawinata A, et al. Impact of steatosis on perioperative outcome following hepatic resection. J Gastrointest Surg. 2003;7:1034–44.

    Article  PubMed  Google Scholar 

  118. Kishi Y, Zorzi D, Contreras CM, et al. Extended preoperative chemotherapy does not improve pathologic response and increases postoperative liver insufficiency after hepatic resection for colorectal liver metastases. Ann Surg Oncol. 2010;17:870–6.

    Google Scholar 

  119. Welsh FK, Tilney HS, Tekkis PP, et al. Safe liver resection following chemotherapy for colorectal metastases is a matter of timing. Br J Cancer. 2007;96:1037–42.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  120. Mitry E, Fields AL, Bleiberg H, et al. Adjuvant chemotherapy after potentially curative resection of metastases from colorectal cancer: a pooled analysis of two randomized trials. J Clin Oncol. 2008;26:4906–11.

    Article  CAS  PubMed  Google Scholar 

  121. Nordlinger B, Sorbye H, Glimelius B, 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;371:1007–16.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  122. Nordlinger B, Sorbye H, Glimelius B, et al. Perioperative FOLFOX4 chemotherapy and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC 40983): long-term results of a randomised, controlled, phase 3 trial. Lancet Oncol. 2013;14:1208–15.

    Article  CAS  PubMed  Google Scholar 

  123. Ychou M, Hohenberger W, Thezenas S, et al. A randomized phase III study comparing adjuvant 5-fluorouracil/folinic acid with FOLFIRI in patients following complete resection of liver metastases from colorectal cancer. Ann Oncol. 2009;20:1964–70.

    Article  CAS  PubMed  Google Scholar 

  124. Primrose J, Falk S, Finch-Jones M, et al. Systemic chemotherapy with or without cetuximab in patients with resectable colorectal liver metastasis: the New EPOC randomised controlled trial. Lancet Oncol. 2014;15:601–11.

    Article  CAS  PubMed  Google Scholar 

  125. Haraldsdottir S, Wu C, Bloomston M, et al. What is the optimal neo-adjuvant treatment for liver metastasis? Ther Adv Med Oncol. 2013;5:221–34.

    Article  PubMed Central  PubMed  Google Scholar 

  126. Adam R, Wicherts DA, de Haas RJ, et al. Complete pathologic response after preoperative chemotherapy for colorectal liver metastases: myth or reality? J Clin Oncol. 2008;26:1635–41.

    Article  PubMed  Google Scholar 

  127. Benoist S, Brouquet A, Penna C, et al. Complete response of colorectal liver metastases after chemotherapy: does it mean cure? J Clin Oncol. 2006;24:3939–45.

    Article  PubMed  Google Scholar 

  128. Blazer 3rd DG, Kishi Y, Maru DM, et al. Pathologic response to preoperative chemotherapy: a new outcome end point after resection of hepatic colorectal metastases. J Clin Oncol. 2008;26:5344–51.

    Article  PubMed  Google Scholar 

  129. Wagman LD. Importance of response to neoadjuvant therapy in patients with liver-limited mCRC when the intent is resection and/or ablation. Clin Colorectal Cancer. 2013;12:223–32.

    Article  PubMed  Google Scholar 

  130. Masi G, Loupakis F, Pollina L, et al. Long-term outcome of initially unresectable metastatic colorectal cancer patients treated with 5-fluorouracil/leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) followed by radical surgery of metastases. Ann Surg. 2009;249:420–5.

    Article  PubMed  Google Scholar 

  131. Ychou M, Rivoire M, Thezenas S, et al. A randomized phase II trial of three intensified chemotherapy regimens in first-line treatment of colorectal cancer patients with initially unresectable or not optimally resectable liver metastases. The METHEP trial. Ann Surg Oncol. 2013;20:4289–97.

    Article  PubMed  Google Scholar 

  132. Folprecht G, Gruenberger T, Bechstein WO, et al. Tumour response and secondary resectability of colorectal liver metastases following neoadjuvant chemotherapy with cetuximab: the CELIM randomised phase 2 trial. Lancet Oncol. 2010;11:38–47.

    Article  CAS  PubMed  Google Scholar 

  133. Ye LC, Liu TS, Ren L, et al. Randomized controlled trial of cetuximab plus chemotherapy for patients with KRAS wild-type unresectable colorectal liver-limited metastases. J Clin Oncol. 2013;31:1931–8.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Hematology and Medical Oncology, Department of Internal Medicine, Mayo Clinic Arizona and Mayo Clinic Cancer Center, Scottsdale, AZ, 85259, USA

    Thorvardur R. Halfdanarson MD

  2. Department of Medical Oncology, Mayo Clinic, Rochester, Rochester, MN, 55905, USA

    Joleen M. Hubbard MD

Authors
  1. Thorvardur R. Halfdanarson MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Joleen M. Hubbard MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Thorvardur R. Halfdanarson MD .

Editor information

Editors and Affiliations

  1. Colon and Rectal Surgery, Yale School of Medicine, New Haven, Connecticut, USA

    Walter E. Longo

  2. Colon and Rectal Surgery, Yale School of Medicine, New Haven, Connecticut, USA

    Vikram Reddy

  3. University of Liverpool St Helens Teaching Hospital, St Helens, United Kingdom

    Riccardo A. Audisio

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer-Verlag London

About this chapter

Cite this chapter

Halfdanarson, T.R., Hubbard, J.M. (2015). Metastatic Rectal Cancer. In: Longo, W., Reddy, V., Audisio, R. (eds) Modern Management of Cancer of the Rectum. Springer, London. https://doi.org/10.1007/978-1-4471-6609-2_20

Download citation

  • DOI: https://doi.org/10.1007/978-1-4471-6609-2_20

  • Published:

  • Publisher Name: Springer, London

  • Print ISBN: 978-1-4471-6608-5

  • Online ISBN: 978-1-4471-6609-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation