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Adjuvant Chemotherapy

  • Toshiaki IshikawaEmail author
  • Hiroyuki Uetake
Chapter

Abstract

Recent remarkable advances in chemotherapy for colorectal cancer are adding new knowledge to adjuvant chemotherapy, but it is not the case that recurrence can be prevented in all patients who undergo this treatment. Treatment should be selected based on the evidence from clinical trials. Herein we present a review of the development of systemic chemotherapy for colorectal cancer (CRC) in the adjuvant treatment settings.

Adjuvant treatment with a fluoropyrimidine plus oxaliplatin has been the standard of care for resected stage III colon cancer. It has been suggested that stage III CRC consists of subgroups of patients with various prognoses and the expected benefits of L-OHP could vary according to subgroup stage. Oral fluoropyrimidine alone treatment might be a considerable option for low-risk patients. Adjuvant treatment for elderly patients who have formerly been excluded from clinical trials must be considered. Although the usefulness of adjuvant chemotherapy for stage II colon cancer remains controversial, guidelines recommend adjuvant chemotherapy for patients with high-risk features.

In rectal cancer, the efficacy of adjuvant chemotherapy has not been established. Although conclusive evidence of the benefits of adjuvant therapy in patients with rectal cancer is unclear, adjuvant chemotherapy is recommended for patients with stage II and stage III rectal cancer.

For resectable metastatic disease, there is no standard treatment and the effective role of systemic adjuvant chemotherapy remains controversial. However, the current international guidelines recommend an adjuvant treatment for patients with initially resectable metastatic disease.

It is necessary to establish the optimal adjuvant chemotherapy corresponding to the conditions of individual patients.

Keywords

Adjuvant chemotherapy Stage III Stage II Fluoropyrimidine Oxaliplatin Elderly patients High risk Biomarker Biological targeted agents 

References

  1. 1.
    National Comprehensive Cancer Network. Clinical practice guidelines in Oncology; colon cancer version 2. 2018. https://www.nccn.org/professionals/physician_gls/pdf/colon.pdf.
  2. 2.
    Labianca R, Nordlinger B, Beretta GD, et al. Early colon cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013;24(Supplement 6):vi64–72.PubMedGoogle Scholar
  3. 3.
    Watanabe T, Muro K, Ajioka Y, et al. Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2016 for the treatment of colorectal cancer. Int J Clin Oncol. 2018;23:1–34.PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Laurie JA, Moertel CG, Fleming TR, et al. Surgical adjuvant therapy of largebowel carcinoma: an evaluation of levamisole and the combination of levamisole and fluorouracil. The North Central Cancer Treatment Group and the Mayo Clinic. J Clin Oncol. 1989;7:1447–56.PubMedCrossRefGoogle Scholar
  5. 5.
    Moertel CG, Fleming TR, Macdonald JS, et al. Levamisole and fluorouracil for adjuvant therapy of resected colon carcinoma. N Engl J Med. 1990;322:352–8.PubMedCrossRefGoogle Scholar
  6. 6.
    Efficacy of adjuvant fluorouracil and folinic acid in colon cancer. International Multicentre Pooled Analysis of Colon Cancer Trials (IMPACT) investigators. Lancet. 1995;345:939–44.Google Scholar
  7. 7.
    Wolmark N, Rockette H, Mamounas E, et al. Clinical trial to assess the relative efficacy of fluorouracil and leucovorin, fluorouracil and levamisole, and fluorouracil, leucovorin, and levamisole in patients with Dukes’ B and C carcinoma of the colon: results from National Surgical Adjuvant Breast and Bowel Project C-04. J Clin Oncol. 1999;17:3553–9.PubMedCrossRefGoogle Scholar
  8. 8.
    Arkenau HT, Bermann A, Rettig K, et al. 5-Fluorouracil plus leucovorin is an effective adjuvant chemotherapy in curatively resected stage III colon cancer: long-term follow-up results of the adjCCA-01 trial. Ann Oncol. 2003;14:395–9.PubMedCrossRefGoogle Scholar
  9. 9.
    Lembersky BC, Wieand HS, Petrelli NJ, et al. Oral uracil and tegafur plus leucovorin compared with intravenous fluorouracil and leucovorin in stage II and III carcinoma of the colon: results from National Surgical Adjuvant Breast and Bowel Project Protocol C-06. J Clin Oncol. 2006;24:2059–64.PubMedCrossRefGoogle Scholar
  10. 10.
    Twelves C, Wong A, Nowacki MP, et al. Capecitabine as adjuvant treatment for stage III colon cancer. N Engl J Med. 2005;352:2696–704.PubMedCrossRefPubMedCentralGoogle Scholar
  11. 11.
    Shimada Y, Hamaguchi T, Mizusawa J, et al. Randomised phase III trial of adjuvant chemotherapy with oral uracil and tegafur plus leucovorin versus intravenous fluorouracil and levofolinate in patients with stage III colorectal cancer who have undergone Japanese D2/D3 lymph node dissection: final results of JCOG0205. Eur J Cancer. 2014;50:2231–40.PubMedCrossRefPubMedCentralGoogle Scholar
  12. 12.
    Yoshida M, Ishiguro M, Ikejiri K, et al. S-1 as adjuvant chemotherapy for stage III colon cancer: a randomized phase III study (ACTS-CC trial). Ann Oncol. 2014;25:1743–9.PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Kuebler JP, Wieand HS, O’Connell MJ, et al. Oxaliplatin combined with weekly bolus fluorouracil and leucovorin as surgical adjuvant chemotherapy for stage II and III colon cancer: results from NSABP C-07. J Clin Oncol. 2007;25:2198–204.PubMedCrossRefPubMedCentralGoogle Scholar
  14. 14.
    Andre T, Boni C, Navarro M, et al. Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial. J Clin Oncol. 2009;27:3109–16.PubMedCrossRefPubMedCentralGoogle Scholar
  15. 15.
    Haller DG, Tabernero J, Maroun J, et al. Capecitabine plus oxaliplatin compared with fluorouracil and folinic acid as adjuvant therapy for stage III colon cancer. J Clin Oncol. 2011;29:1465–71.PubMedCrossRefPubMedCentralGoogle Scholar
  16. 16.
    Saltz LB, Niedzwiecki D, Hollis D, et al. Irinotecan fluorouracil plus leucovorin is not superior to fluorouracil plus leucovorin alone as adjuvant treatment for stage III colon cancer: results of CALGB 89803. J Clin Oncol. 2007;25:3456–61.PubMedCrossRefPubMedCentralGoogle Scholar
  17. 17.
    Van Cutsem E, Labianca R, Bodoky G, et al. Randomized phase III trial comparing biweekly infusional fluorouracil/leucovorin alone or with irinotecan in the adjuvant treatment of stage III colon cancer: PETACC-3. J Clin Oncol. 2009;27:3117–25.PubMedCrossRefPubMedCentralGoogle Scholar
  18. 18.
    Allegra CJ, Yothers G, O’Connell MJ, et al. Phase III trial assessing bevacizumab in stages II and III carcinoma of the colon: results of NSABP protocol C-08. J Clin Oncol. 2011;29:11–6.PubMedCrossRefPubMedCentralGoogle Scholar
  19. 19.
    de Gramont A, Van Cutsem E, Schmoll HJ, et al. Bevacizumab plus oxaliplatinbased chemotherapy as adjuvant treatment for colon cancer (AVANT): a phase 3 randomised controlled trial. Lancet Oncol. 2012;13:1225–33.PubMedCrossRefPubMedCentralGoogle Scholar
  20. 20.
    Kerr RS, Love S, Segelov E, et al. Adjuvant capecitabine plus bevacizumab versus capecitabine alone in patients with colorectal cancer (QUASAR 2): an open-label, randomised phase 3 trial. Lancet Oncol. 2016;17:1543–57.PubMedCrossRefGoogle Scholar
  21. 21.
    Alberts SR, Sargent DJ, Nair S, et al. Effect of oxaliplatin, fluorouracil and leucovorin with or without cetuximab on survival among patients with resected stage III colon cancer: a randomized trial. JAMA. 2012;307:1383–93.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Taieb J, Tabernero J, Mini E, et al. Oxaliplatin, fluorouracil, and leucovorin with or without cetuximab in patients with resected stage III colon cancer (PETACC-8): an open-label, randomised phase 3 trial. Lancet Oncol. 2014;15:862–73.PubMedCrossRefGoogle Scholar
  23. 23.
    Andre T, Quinaux E, Louvet C, et al. Phase III study comparing a semimonthly with a monthly regimen of fluorouracil and leucovorin as adjuvant treatment for stage II and III colon cancer patients: final results of GERCOR C96.1. J Clin Oncol. 2007;25:3732–8.PubMedCrossRefPubMedCentralGoogle Scholar
  24. 24.
    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.PubMedCrossRefPubMedCentralGoogle Scholar
  25. 25.
    Hamaguchi T, Shimada Y, Mizusawa J, et al. Capecitabine versus S-1 as adjuvant chemotherapy for patients with stage III colorectal cancer (JCOG0910): an open-label, non-inferiority, randomised, phase 3, multicentre trial. Lancet Gastroenterol Hepatol. 2018;3:47–56.PubMedCrossRefPubMedCentralGoogle Scholar
  26. 26.
    Schmoll HJ, Twelves C, Sun W, et al. Effect of adjuvant capecitabine or fluorouracil, with or without oxaliplatin, on survival outcomes in stage III colon cancer and the effect of oxaliplatin on post-relapse survival: a pooled analysis of individual patient data from four randomised controlled trials. Lancet Oncol. 2014;15:1481–92.PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    de Gramont A, Chibaudel B, Bachet JB, et al. From chemotherapy to targeted therapy in adjuvant treatment for stage III colon cancer. Semin Oncol. 2011;38:521–32.PubMedCrossRefPubMedCentralGoogle Scholar
  28. 28.
    Tournigand C, André T, Bonnetain F, et al. Adjuvant therapy with fluorouracil and oxaliplatin in stage II and elderly patients (between ages 70 and 75 years) with colon cancer: subgroup analyses of the Multicenter International Study of Oxaliplatin, Fluorouracil, and Leucovorin in the Adjuvant Treatment of Colon Cancer Trial. J Clin Oncol. 2012;30:3353–60.PubMedCrossRefPubMedCentralGoogle Scholar
  29. 29.
    McCleary NJ, Meyerhardt JA, Green E, et al. Impact of age on the efficacy of newer adjuvant therapies in patients with stage II/III colon cancer: findings from the ACCENT database. J Clin Oncol. 2013;31:2600–6.PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Biagi JJ, Raphael MJ, Mackillop WJ, et al. Association between time to initiation of adjuvant chemotherapy and survival in colorectal cancer: a systematic review and meta-analysis. JAMA. 2011;305:2335–42.PubMedCrossRefGoogle Scholar
  31. 31.
    Des Guetz G, Nicolas P, Perret GY, et al. Does delaying adjuvant chemotherapy after curative surgery for colorectal cancer impair survival? A meta-analysis. Eur J Cancer. 2010;46(6):1049–55.PubMedCrossRefGoogle Scholar
  32. 32.
    Andre T, Colin P, Louvet C, et al. Semimonthly versus monthly regimen of fluorouracil and leucovorin administered for 24 or 36 weeks as adjuvant therapy in stage II and III colon cancer: results of a randomized trial. J Clin Oncol. 2003;21:2896–903.PubMedCrossRefGoogle Scholar
  33. 33.
    Grothey A, Sobrero AF, Shields AF, et al. Duration of adjuvant chemotherapy for stage III colon cancer. N Engl J Med. 2018;378:1177–88.PubMedCrossRefGoogle Scholar
  34. 34.
    Jessup JM, Stewart A, Greene FL, et al. Adjuvant chemotherapy for stage III colon cancer: implications of race/ethnicity, age, and differentiation. JAMA. 2005;7(294):2703–11.CrossRefGoogle Scholar
  35. 35.
    Sanoff HK, Carpenter WR, Stürmer T, et al. Effect of adjuvant chemotherapy on survival of patients with stage III colon cancer diagnosed after age 75 years. J Clin Oncol. 2012;30:2624–34.PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Sargent DJ, Goldberg RM, Jacobson SD, et al. A pooled analysis of adjuvant chemotherapy for resected colon cancer in elderly patients. N Engl J Med. 2001;345:1091–7.PubMedCrossRefPubMedCentralGoogle Scholar
  37. 37.
    Tournigand C, André T, Bonnetain F, et al. Adjuvant therapy with fluorouracil and oxaliplatin in stage II and elderly patients (between ages 70 and 75 years) with colon cancer: subgroup analyses of the Multicenter International Study of Oxaliplatin, Fluorouracil, and Leucovorin in the Adjuvant Treatment of Colon Cancer trial. J Clin Oncol. 2012;30:3353–60.PubMedCrossRefPubMedCentralGoogle Scholar
  38. 38.
    Yothers G, O’Connell MJ, Allegra CJ, et al. Oxaliplatin as adjuvant therapy for colon cancer: updated results of NSABP C-07 trial, including survival and subset analyses. J Clin Oncol. 2011;29:3768–74.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Sanoff HK, Carpenter WR, Martin CF, et al. Comparative effectiveness of oxaliplatin vs non-oxaliplatin-containing adjuvant chemotherapy for stage III colon cancer. J Natl Cancer Inst. 2012;104:211–27.PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Haller DG, O’Connell MJ, Cartwright TH, et al. Impact of age and medical comorbidity on adjuvant treatment outcomes for stage III colon cancer: a pooled analysis of individual patient data from four randomized, controlled trials. Ann Oncol. 2015;26:715–24.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Kannarkatt J, Joseph J, Kurniali PC, et al. Adjuvant chemotherapy for stage II colon cancer: a clinical dilemma. J Oncol Pract. 2017;13:233–41.PubMedCrossRefGoogle Scholar
  42. 42.
    Mamounas E, Wieand S, Wolmark N, et al. Comparative efficacy of adjuvant chemotherapy in patients with Dukes’ B versus Dukes’ C colon cancer: results from four National Surgical Adjuvant Breast and Bowel Project adjuvant studies (C-01, C-02, C-03, and C-04). J Clin Oncol. 1999;17:1349–55.PubMedCrossRefGoogle Scholar
  43. 43.
    Sakamoto J, Ohashi Y, Hamada C, et al. Efficacy of oral adjuvant therapy after resection of colorectal cancer: 5-year results from three randomized trials. J Clin Oncol. 2004;22:484–92.PubMedCrossRefGoogle Scholar
  44. 44.
    Böckelman C, Engelmann BE, Kaprio T, et al. Risk of recurrence in patients with colon cancer stage II and III: a systematic review and meta-analysis of recent literature. Acta Oncol. 2015;54:5–16.PubMedCrossRefGoogle Scholar
  45. 45.
    Casadaban L, Rauscher G, Aklilu M, et al. Adjuvant chemotherapy is associated with improved survival in patients with stage II colon cancer. Cancer. 2016;122:3277–87.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Matsuda C, Ishiguro M, Teramukai S, et al. A randomized-controlled trial of 1-year adjuvant chemotherapy with oral tegafur-uracil versus surgery alone in stage II colon cancer: SACURA trial. Eur J Cancer. 2018;96:54–63.PubMedCrossRefGoogle Scholar
  47. 47.
    André T, de Gramont A, Vernerey D, et al. Adjuvant fluorouracil, leucovorin, and oxaliplatin in stage II to III colon cancer: updated 10-year survival and outcomes according to BRAF mutation and mismatch repair status of the MOSAIC study. J Clin Oncol. 2015;33:4176–87.PubMedCrossRefGoogle Scholar
  48. 48.
    Ribic CM, Sargent DJ, Moore MJ, et al. Tumor microsatellite instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer. N Engl J Med. 2003;349:247–57.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Sargent DJ, Marsoni S, Monges G, et al. Defective mismatch repair as a predictive marker for the lack of efficacy of fluorouracil-based adjuvant therapy in colon cancer. J Clin Oncol. 2010;28:3219–26.PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Sinicrope FA, Foster NR, Thibodeau SN, et al. DNA mismatch repair status and colon cancer recurrence and survival in clinical trials of 5-fluorouracil-based adjuvant therapy. J Natl Cancer Inst. 2011;103:863–75.PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Tejpar S, Saridaki Z, Delorenzi M, et al. Microsatellite instability, prognosis and drug sensitivity of stage II and III colorectal cancer: more complexity to the puzzle. J Natl Cancer Inst. 2011;103:841–4.PubMedCrossRefPubMedCentralGoogle Scholar
  52. 52.
    Roth AD, Delorenzi M, Tejpar S, et al. Integrated analysis of molecular and clinical prognostic factors in stage II/III colon cancer. J Natl Cancer Inst. 2012;104:1635–46.PubMedCrossRefPubMedCentralGoogle Scholar
  53. 53.
    Jen J, Kim H, Piantadosi S, et al. Allelic loss of chromosome 18q and prognosis in colorectal cancer. N Engl J Med. 1994;331:213–21.PubMedCrossRefPubMedCentralGoogle Scholar
  54. 54.
    Watanabe T, Wu TT, Catalano PJ, et al. Molecular predictors of survival after adjuvant chemotherapy for colon cancer. N Engl J Med. 2001;344:1196–206.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Ogino S, Nosho K, Irahara N, et al. Prognostic significance and molecular associations of 18q loss of heterozygosity: a cohort study of microsatellite stable colorectal cancers. J Clin Oncol. 2009;27:4591–8.PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Bertagnolli MM, Redston M, Compton CC, et al. Microsatellite instability and loss of heterozygosity at chromosomal location 18q: prospective evaluation of biomarkers for stages II and III colon cancer—a study of CALGB 9581 and 89803. J Clin Oncol. 2011;29:3153–62.PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Gray RG, Quirke P, Handley K, et al. Validation study of a quantitative multigene reverse transcriptase-polymerase chain reaction assay for assessment of recurrence risk in patients with stage II colon cancer. J Clin Oncol. 2011;29:4611–9.PubMedCrossRefPubMedCentralGoogle Scholar
  58. 58.
    Yothers G, O’Connell MJ, Lee M, et al. Validation of the 12-gene colon cancer recurrence score in NSABP C-07 as a predictor of recurrence in patients with stage II and III colon cancer treated with fluorouracil and leucovorin (FU/LV) and FU/LV plus oxaliplatin. J Clin Oncol. 2013;31:4512–9.PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Kopetz S, Tabernero J, Rosenberg R, et al. Genomic classifier ColoPrint predicts recurrence in stage II colorectal cancer patients more accurately than clinical factors. Oncologist. 2015;20:127–33.PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    National Comprehensive Cancer Network. Clinical practice guidelines in Oncology; rectal cancer version 2. 2018. https://www.nccn.org/professionals/physician_gls/pdf/rectal.pdf.
  61. 61.
    Glynne-Jones R, Wyrwicz L, Tiret E, et al. Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017;28(suppl_4):iv22–40.PubMedCrossRefGoogle Scholar
  62. 62.
    Quasar Collaborative Group, Gray R, Barnwell J, et al. Adjuvant chemotherapy versus observation in patients with colorectal cancer: a randomized study. Lancet. 2007;370:2020–9.CrossRefGoogle Scholar
  63. 63.
    Akasu T, Moriya Y, Ohashi Y, et al. Adjuvant chemotherapy with uracil-tegafur for pathological stage III rectal cancer after mesorectal excision with selective lateral pelvic lymphadenectomy: a multicenter randomized controlled trial. Jpn J Clin Oncol. 2006;36:237–44.PubMedCrossRefGoogle Scholar
  64. 64.
    Oki E, Murata A, Yoshida K, et al. A randomized phase III trial comparing S-1 versus UFT as adjuvant chemotherapy for stage II/III rectal cancer (JFMC35-C1: ACTS-RC). Ann Oncol. 2016;27:1266–72.PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Petersen SH, Harling H, Kirkeby LT, et al. Postoperative adjuvant chemotherapy in rectal cancer operated for cure. Cochrane Database Syst Rev. 2012;3:CD004078.Google Scholar
  66. 66.
    Sainato A, Cernusco Luna Nunzia V, Valentini V, et al. No benefit of adjuvant fluorouracil leucovorin chemotherapy after neoadjuvant chemoradiotherapy in locally advanced cancer of the rectum (LARC): long term results of a randomized trial (I-CNR-RT). Radiother Oncol. 2014;113:223–9.PubMedCrossRefPubMedCentralGoogle Scholar
  67. 67.
    Breugom AJ, van Gijn W, Muller EW, et al. Adjuvant chemotherapy for rectal cancer patients treated with preoperative (chemo)radiotherapy and total mesorectal excision: a Dutch Colorectal Cancer Group (DCCG) randomised phase III trial. Ann Oncol. 2015;26:696–701.CrossRefGoogle Scholar
  68. 68.
    Breugom AJ, Swets M, Bosset JF, et al. Adjuvant chemotherapy after preoperative (chemo)radiotherapy and surgery for patients with rectal cancer: a systematic review and meta-analysis of individual patient data. Lancet Oncol. 2015;16:200–7.PubMedCrossRefPubMedCentralGoogle Scholar
  69. 69.
    Rödel C, Graeven U, Fietkau R, et al. Oxaliplatin added to fluorouracil-based preoperative chemoradiotherapy and postoperative chemotherapy of locally advanced rectal cancer (the German CAO/ARO/AIO-04 study): final results of the multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2015;16(8):979–89.PubMedCrossRefGoogle Scholar
  70. 70.
    Zhao L, Liu R, Zhang Z, et al. Oxaliplatin/fluorouracil-based adjuvant chemotherapy for locally advanced rectal cancer after neoadjuvant chemoradiotherapy and surgery: a systematic review and meta-analysis of randomized controlled trials. Color Dis. 2016;18:763–72.CrossRefGoogle Scholar
  71. 71.
    Glynne-Jones R, Counsell N, Quirke P, et al. Chronicle: results of a randomised phase III trial in locally advanced rectal cancer after neoadjuvant chemoradiation randomising postoperative adjuvant capecitabine plus oxaliplatin (XELOX) versus control. Ann Oncol. 2014;25:1356–62.PubMedCrossRefGoogle Scholar
  72. 72.
    Chau I, Brown G, Cunningham D, et al. Neoadjuvant capecitabine and oxaliplatin followed by synchronous chemoradiation and total mesorectal excision in magnetic resonance imaging-defined poor-risk rectal cancer. J Clin Oncol. 2006;24:668–74.PubMedCrossRefGoogle Scholar
  73. 73.
    Fernandez-Martos C, Garcia-Albeniz X, Pericay C, et al. Chemoradiation, surgery and adjuvant chemotherapy versus induction chemotherapy followed by chemoradiation and surgery: long-term results of the Spanish GCR-3 phase II randomized trial†. Ann Oncol. 2015;26:1722–8.PubMedCrossRefGoogle Scholar
  74. 74.
    Maréchal R, Vos B, Polus M, Delaunoit T, et al. Short course chemotherapy followed by concomitant chemoradiotherapy and surgery in locally advanced rectal cancer: a randomized multicentric phase II study. Ann Oncol. 2012;23:1525–30.PubMedCrossRefGoogle Scholar
  75. 75.
    Nogué M, Salud A, Vicente P, et al. Addition of bevacizumab to XELOX induction therapy plus concomitant capecitabine-based chemoradiotherapy in magnetic resonance imaging-defined poor-prognosis locally advanced rectal cancer: the AVACROSS study. Oncologist. 2011;16:614–20.PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Schmoll HJ, Van Cutsem E, Stein A, et al. ESMO Consensus Guidelines for management of patients with colon and rectal cancer. A personalized approach to clinical decision making. Ann Oncol. 2012;23(10):2479–516.PubMedCrossRefGoogle Scholar
  77. 77.
    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;20(26):4906–11.CrossRefGoogle Scholar
  78. 78.
    Hasegawa K, Saiura A, Takayama T, et al. Adjuvant oral uracil-tegafur with leucovorin for colorectal cancer liver metastases: a randomized controlled trial. PLoS One. 2016;11(9):e0162400.PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    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): longterm results of a randomised, controlled, phase 3 trial. Lancet Oncol. 2013;14:1208–15.PubMedCrossRefPubMedCentralGoogle Scholar
  80. 80.
    Kanemitsu Y, Kato T, Shimizu Y, Inaba Y, et al. A randomized phase II/III trial comparing hepatectomy followed by mFOLFOX6 with hepatectomy alone as treatment for liver metastasis from colorectal cancer: Japan Clinical Oncology Group Study JCOG0603. Jpn J Clin Oncol. 2009;39:406–9.PubMedCrossRefPubMedCentralGoogle Scholar
  81. 81.
    Ciliberto D, Prati U, Roveda L, Barbieri V, et al. Role of systemic chemotherapy in the management of resected or resectable colorectal liver metastases: a systematic review and meta-analysis of randomized controlled trials. Oncol Rep. 2012;27:1849–56.PubMedPubMedCentralGoogle Scholar
  82. 82.
    Wang ZM, Chen YY, Chen FF, et al. Peri-operative chemotherapy for patients with resectable colorectal hepatic metastasis: a meta-analysis. Eur J Surg Oncol. 2015;41:1197–203.PubMedCrossRefPubMedCentralGoogle Scholar
  83. 83.
    Araujo RL, Gönen M, Herman P. Chemotherapy for patients with colorectal liver metastases who underwent curative resection improves long-term outcomes: systematic review and meta-analysis. Ann Surg Oncol. 2015;22:3070–8.PubMedCrossRefGoogle Scholar
  84. 84.
    Khoo E, O’Neill S, Brown E, et al. Systematic review of systemic adjuvant, neoadjuvant and perioperative chemotherapy for resectable colorectal-liver metastases. HPB (Oxford). 2016;18:485–93.CrossRefGoogle Scholar
  85. 85.
    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.PubMedCrossRefGoogle Scholar
  86. 86.
    Snoeren N, van Hillegersberg R, Schouten SB, et al. Randomized phase III study to assess efficacy and safety of adjuvant CAPOX with or without bevacizumab in patients after resection of colorectal liver metastases: HEPATICA study. Neoplasia. 2017;19:93–9.PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    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 randomized controlled trial. Lancet Oncol. 2014;15:601–11.PubMedCrossRefGoogle Scholar

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© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Department of Specialized SurgeriesTokyo Medical and Dental University, Graduate School of Medicine and DentistryTokyoJapan

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