Skip to main content
SpringerLink
Log in

Chemotherapy and molecular-targeted treatment for unresectable hepatic metastases: a Japanese perspective

  • Topics
  • Therapeutic strategies for hepatic metastasis of colorectal cancer: 2011 Update
  • Published:
Journal of Hepato-Biliary-Pancreatic Sciences

Abstract

Liver metastasis from colorectal cancer has become a common disease associated with the increase of primary colorectal cancer in Japan. The standard treatment for resectable liver metastases is still complete liver resection. Recent advances in systemic chemotherapy have introduced another strategy, i.e., conversion chemotherapy, for patients with initially diagnosed unresectable liver metastases. The conversion rate after neo-adjuvant chemotherapy is increasing with multidisciplinary approaches. Long-term clinical data have not been established yet. Indications for liver resection after neo-adjuvant chemotherapy; optimal chemotherapy regimens; and histological changes in the normal liver are important research issues for the future.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Notes

  1. A Phase III trial of 5-FU/l-leucovorin/irinotecan (FOLFIRI) versus irinotecan/S-1 (IRIS) as second-line chemotherapy for metastatic colorectal cancer

  2. A Randomized Phase III Trial of S-1/Oxaliplatin (SOX) plus Bevacizumab versus 5-FU/l-LV/Oxaliplatin (FOLFOX) plus Bevacizmab in Treating Patients with Metastatic Colorectal Cancer

References

  1. CANCER STATISTICS in JAPAN ’09. http://ganjoho.jp/public/statistics/backnumber/2010_en.html.

  2. Watanabe T, Itabashi M, Shimada Y, Tanaka S, Ito Y, Ajioka Y, et al. Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2010 for the treatment of colorectal cancer. Int J Clin Oncol. 2012;17(1):1–29. doi:10.1007/s10147-011-0315-2.

    Article  PubMed  Google Scholar 

  3. Minagawa M, Makuuchi M, Torzilli G, Takayama T, Kawasaki S, Kosuge T, et al. Extension of the frontiers of surgical indications in the treatment of liver metastases from colorectal cancer: long-term results. Ann Surg. 2000;231(4):487–99.

    Article  PubMed  CAS  Google Scholar 

  4. Kato T, Yasui K, Hirai T, Kanemitsu Y, Mori T, Sugihara K, et al. Therapeutic results for hepatic metastasis of colorectal cancer with special reference to effectiveness of hepatectomy: analysis of prognostic factors for 763 cases recorded at 18 institutions. Dis Colon Rectum. 2003;46(10 Suppl):S22–31.

    PubMed  Google Scholar 

  5. Lievre A, Bachet JB, Boige V, Cayre A, Le Corre D, Buc E, et al. KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab. J Clin Oncol. 2008;26:374–9.

    Article  PubMed  CAS  Google Scholar 

  6. Van Cutsem E, Kohne CH, Lang I, Folprecht G, Nowacki MP, Cascinu S, 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  Google Scholar 

  7. Van Cutsem E, Hohne CH, Hitre E, Zaluski J, Chang Chien CR, Makhson A, et al. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med. 2009;360:1408–17.

    Article  PubMed  Google Scholar 

  8. Scheithauer W, Rosen H, Kornek GV, Sebesta C, Depisch D. Randomised comparison of combination chemotherapy plus supportive care with supportive care alone in patients with metastatic colorectal cancer. BMJ. 1993;306:752–5.

    Article  PubMed  CAS  Google Scholar 

  9. Saltz LB, Clarke S, Diaz-Rubio E, Scheithauer W, Figer A, Wong R, 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  PubMed  CAS  Google Scholar 

  10. Muro K, Boku N, Shimada Y, Tsuji A, Sameshima S, Baba H, et al. Irinotecan plus S-1 (IRIS) versus fluorouracil and folinic acid plus irinotecan (FOLFIRI) as second-line chemotherapy for metastatic colorectal cancer: a randomized phase 2/3 non-inferiority study (FIRIS study). L. Lancet Oncol. 2010;11:853–60.

    Article  PubMed  CAS  Google Scholar 

  11. Power DG, Kemeny NE. Role of adjuvant therapy after resection of colorectal cancer liver metastases. J Clin Oncol. 2010;28:2300–9.

    Article  PubMed  CAS  Google Scholar 

  12. Kemeny N, Jarnagin W, Gonen M, Stockman J, Blumgart L, Sperber D, et al. Phase I/II study of hepatic arterial therapy with floxuridine and dexamethasone in combination with intravenous irinotecan as adjuvant treatment after resection of hepatic metastases from colorectal cancer. J Clin Oncol. 2003;21:3303–9.

    Article  PubMed  CAS  Google Scholar 

  13. House MG, Kemeny NE, Gönen M, Fong Y, Allen PJ, Paty PB, et al. Comparison of adjuvant systemic chemotherapy with or without hepatic arterial infusional chemotherapy after hepatic resection for metastatic colorectal cancer. Ann Surg. 2011;254:851–6.

    Article  PubMed  Google Scholar 

  14. Mitry E, Fields AL, Bleiberg H, Labianca R, Portier G, Tu D, 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  PubMed  CAS  Google Scholar 

  15. Portier G, Elias D, Bouche O, Rougier P, Bosset JF, Saric J, et al. Multicenter randomized trial of adjuvant fluorouracil and folinic acid compared with surgery alone after resection of colorectal liver metastases: FFCD ACHBTH AURC 9002 trial. J Clin Oncol. 2006;24:4976–82.

    Article  PubMed  CAS  Google Scholar 

  16. Nordlinger B, Sorbye H, Glimelius B, Poston GJ, Schlag PM, Rougier P, et al. Perioperative chemotherapy with FOLFOX4 and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC intergroup trial 40983): a randomized controlled trial. Lancet. 2008;371:1007–16.

    Article  PubMed  CAS  Google Scholar 

  17. Kanemitsu Y, Kato T, Shimizu Y, Inaba Y, Shimada Y, Nakamura K, et al. A randomized phase II/III trial comparing hepatectomy followed by mFOLFOX6 with hepatectomy alone as treatment for liver metastases from colorectal cancer: Japan Clinical Oncology Group study JCOG 0603. Jpn J Clin Oncol. 2009;39:406–9.

    Article  PubMed  Google Scholar 

  18. Folprecht G, Gruenberger T, Bechstein WO, Raab HR, Lordick F, Hartmann JT, et al. Tumor response and secondary resectability of colorectal liver metastases following neoadjuvant chemotherapy with cetuximab: the CELIM randomized phase 2 trial. Lancet Oncol. 2010;11:38–47.

    Article  PubMed  CAS  Google Scholar 

  19. Bismuth H, Adam R. Reduction of non-resectable liver metastasis from colorectal cancer after oxaliplatin chemotherapy. Semin Oncol. 1998;25(Suppl 5):40–46.

    Google Scholar 

  20. Folprecht G, Gruenberger T, Bechstein W, Lordick F, Lang H, Weitz J, et al. Progression free and overall survival after neo-adjuvant treatment of colorectal liver metastases with cetuximab plus FOLFOX or FOLFIRI—results of the CELIM study. Eur J Cancer. 2011;47 Suppl 1:S394 (abst 6009).

  21. Lam VW, Spiro C, Laurence JM, Johnston E, Hollands MJ, Pleass HC, et al. A systematic review of clinical response and survival outcomes of downsizing systemic chemotherapy and rescue liver surgery in patients with initially unresectable colorectal liver metastases. Ann Surg Oncol. 2012;19(4):1292–301.

    Google Scholar 

  22. Bilchik AJ, Poston G, Curley SA, Strasberg S, Saltz L, Adam R, et al. Neoadjuvant chemotherapy for metastatic colon cancer: a cautionary note. J Clin Oncol. 2005;23:9073–8.

    Article  PubMed  CAS  Google Scholar 

  23. Rubbia-Brandt L, Audard V, Sartoretti P, Roth AD, Brezault C, Le Charpentier M, et al. Severe hepatic sinusoidal obstruction associated with oxaliplatin-based chemotherapy in patients with metastatic colorectal cancer. Ann Oncol. 2004;15:460–6.

    Article  PubMed  CAS  Google Scholar 

  24. Adam R, Sebagh M, Plasse M, Karam V, Giachetti S, Azoulay D, et al. Impact of preoperative systemic chemotherapy on liver histology and outcome of hepatic resection for colorectal cancer liver metastases (CRLM). J Clin Oncol. 2005;23 Suppl 15:253S (abst 3529).

  25. Fernandez FG, Ritter J, Goodwin JW, Linehan DC, Hawkins WG, Strasberg SM. Effect of steatohepatitis associated with irinotecan or oxaliplatin pre-treatment on resectability of hepatic colorectal metastases. J Am Coll Surg. 2005;200:845–53.

    Article  PubMed  Google Scholar 

  26. Kooby DA, Fong Y, Suriawinata A, Gonen M, Allen PJ, Klimstra DS, et al. Impact of steatosis on perioperative outcome following hepatic resection. J Gastrointest Surg. 2003;7:1034–44.

    Article  PubMed  Google Scholar 

  27. Bokemeyer C, Bondarenko I, Makhson A, Hartmann JT, Aparicio J, de Braud F, et al. Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer. J Clin Oncol. 2009;27:663–71.

    Article  PubMed  CAS  Google Scholar 

  28. Adams RA, Meade AM, Seymour MT, Wilson RH, Madi A, Fisher D, et al. Intermittent versus continuous oxaliplatin and fluoropyrimidines combination chemotherapy for first-line treatment of advanced colorectal cancer: results of the randomized phase 3 MRC COIN trial. Lancet Oncol. 2011;12:642–53.

    Article  PubMed  CAS  Google Scholar 

  29. Tveit K, Guren T, Glimelius B, Pfeiffer H, Sorbye S, Pyrhonen E et al. Randomized phase III study of 5-fluorouracil/folinate/oxaliplatin given continuously or intermittently with or without cetuximab, as first-line treatment of metastatic colorectal cancer: The Nordic VII study (NCT 00145314), by the Nordic colorectal cancer biomodulation group. Ann Oncol. 2010;21 Suppl 8:viii9 LBA20.

  30. Douillard JY, Siena S, Cassidy J, Tabernero J, Burkes R, Barugel M, et al. Randomized phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: The PRIME study. J Clin Oncol. 2010;28:4697–705.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Gastrointestinal Oncology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

    Yasuhiro Shimada

Authors
  1. Yasuhiro Shimada
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yasuhiro Shimada.

About this article

Cite this article

Shimada, Y. Chemotherapy and molecular-targeted treatment for unresectable hepatic metastases: a Japanese perspective. J Hepatobiliary Pancreat Sci 19, 515–522 (2012). https://doi.org/10.1007/s00534-012-0517-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00534-012-0517-7

Keywords

Search

Navigation