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Bevacizumab plus FOLFIRI or FOLFOX as third-line or later treatment in patients with metastatic colorectal cancer after failure of 5-fluorouracil, irinotecan, and oxaliplatin: a retrospective analysis

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Abstract

Bevacizumab, a monoclonal antibody against vascular endothelial growth factor, has shown clinical activity in metastatic colorectal cancer patients when used as either a first-line or second-line treatment. Here, we evaluated the efficacy and safety of bevacizumab plus FOLFIRI (irinotecan, 5-fluorouracil, and leucovorin) or FOLFOX (oxaliplatin, 5-fluorouracil, and leucovorin) in metastatic colorectal cancer cases after failure to FOLFIRI and FOLFOX. Between October 2004 and February 2007, the data on 42 patients with metastatic colorectal cancer after failure of FOLFIRI and FOLFOX were reviewed retrospectively. All patients were treated with bevacizumab plus FOLFIRI or FOLFOX. The median patient age was 57.0 years. The ECOG performance status was 0 or 1 in 27 patients (64.3%). The number of previous chemotherapy regimens was ≥3 in 35 patients (83.3%). Thirty-nine patients were evaluable for response. Four patients had partial responses (PRs) and no patient had a complete response (CR), giving an overall response rate of 9.5%. Twenty-two patients (52.4%) had stable disease and 13 patients (31.0%) showed progressive disease. With a median follow-up time of 12.9 months (range 1.0–30.0 months), the median progression-free survival time and the median overall survival time were 5.3 and 9.5 months, respectively. Grade 3 or 4 neutropenia developed in 18 patients (42.9%), including febrile neutropenia in 4 patients (9.5%). Common non-hematologic toxicities were fatigue (21.4%), neuropathy (21.4%), and mucositis (21.4%). Grade 2 or 3 hypertension occurred in 4 patients (9.6%), and grade 1 or 2 proteinuria was seen in 16 patients (38.1%). The frequencies of adverse events related BV, such as bleeding, thrombosis, and gastrointestinal perforation, were within the ranges of previous reports. However, there were no treatment-related deaths. The combination of bevacizumab plus FOLFIRI or FOLFOX showed modest activity and was relatively tolerable in patients with metastatic colorectal cancer refractory to both FOLFIRI and FOLFOX.

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References

  1. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, et al. Cancer statistics. CA Cancer J Clin. 2008;58:71–96.

    Article  PubMed  Google Scholar 

  2. Shin HR, Jung KW, Won YJ, Park JG. Annual report of the Korea central cancer registry: based on registered data from 139 hospitals. Cancer Res Treat. 2004;36:103–14.

    Article  Google Scholar 

  3. Pawlik TM, Choti MA. Surgical therapy for colorectal metastases to the liver. J Gastrointest Surg. 2007;11:1057–77. doi:10.1007/s11605-006-0061-3.

    Article  PubMed  Google Scholar 

  4. Grothey A, Sargent D, Goldberg RM, Schmoll HJ. 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. doi:10.1200/JCO.2004.11.037.

    Article  PubMed  CAS  Google Scholar 

  5. Meyerhardt JA, Mayer RJ. Systemic therapy for colorectal cancer. N Engl J Med 2005;352:476–87. doi:10.1056/NEJMra040958.

    Article  PubMed  CAS  Google Scholar 

  6. Ragnhammar P, Hafstrom L, Nygren P, Glimelius B. A systematic overview of chemotherapy effects in colorectal cancer. Acta Oncol. 2001;40:282–308.

    Article  PubMed  CAS  Google Scholar 

  7. Ferrara N. Molecular and biological properties of vascular endothelial growth factor. J Mol Med 1999;77:527–43. doi:10.1007/s001099900019.

    Article  PubMed  CAS  Google Scholar 

  8. Gordon MS. Vascular endothelial growth factor as a target for antiangiogenic therapy. J Clin Oncol. 2000;18 Suppl 21:S45–6.

    Google Scholar 

  9. Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004;350:2335–42. doi:10.1056/NEJMoa032691.

    Article  PubMed  CAS  Google Scholar 

  10. Giantonio BJ, Catalano PJ, Meropol NJ, O'Dwyer PJ, Mitchell EP, Alberts SR, et al. Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200. J Clin Oncol. 2007;25:1539–44. doi:10.1200/JCO.2006.09.6305.

    Article  PubMed  CAS  Google Scholar 

  11. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, 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;92:205–16. doi:10.1093/jnci/92.3.205.

    Article  PubMed  CAS  Google Scholar 

  12. Lim DH, Park YS, Park BB, Ji SH, Lee J, Park KW, et al. Mitomycin-C and capecitabine as third-line chemotherapy in patients with advanced colorectal cancer: a phase II study. Cancer Chemother Pharmacol. 2005;56:10–4. doi:10.1007/s00280-004-0963-2.

    Article  PubMed  CAS  Google Scholar 

  13. Ardavanis AS, Ioannidis GN, Orphanos GS, Rigatos GA. Salvage treatment with single-agent capecitabine in patients with heavily pretreated advanced colorectal cancer. Anticancer Res. 2006;26:1669–72.

    PubMed  CAS  Google Scholar 

  14. Gubanski M, Naucler G, Almerud A, Lidestahl A, Lind PA. Capecitabine as third line therapy in patients with advanced colorectal cancer. Acta Oncol 2005;44:236–9.

    Article  PubMed  CAS  Google Scholar 

  15. Rosati G, Rossi A, Germano D, Reggiardo G, Manzione L. Raltitrexed and mitomycin-C as third-line chemotherapy for colorectal cancer after combination regimens including 5-fluorouracil, irinotecan and oxaliplatin: a phase II study. Anticancer Res. 2003;23:2981–5.

    PubMed  CAS  Google Scholar 

  16. Pfeiffer P, Nielsen D, Yilmaz M, Iversen A, Vejlo C, Jensen BV. Cetuximab and irinotecan as third line therapy in patients with advanced colorectal cancer after failure of irinotecan, oxaliplatin and 5-fluorouracil. Acta Oncol. 2007;46:697–701. doi:10.1080/02841860601009455.

    Article  PubMed  CAS  Google Scholar 

  17. Vincenzi B, Santini D, Rabitti C, Coppola R, Beomonte Zobel B, Trodella L, et al. Cetuximab and irinotecan as third-line therapy in advanced colorectal cancer patients: a single centre phase II trial. Br J Cancer. 2006;94:792–7. doi:10.1038/sj.bjc.6603018.

    Article  PubMed  CAS  Google Scholar 

  18. Jonker DJ, O'Callaghan CJ, Karapetis CS, Zalcberg JR, Tu D, Au HJ, et al. Cetuximab for the treatment of colorectal cancer. N Engl J Med. 2007;357:2040–8. doi:10.1056/NEJMoa071834.

    Article  PubMed  CAS  Google Scholar 

  19. Van Cutsem E, Peeters M, Siena S, Humblet Y, Hendlisz A, Neyns B, 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. doi:10.1200/JCO.2006.08.1620.

    Article  PubMed  CAS  Google Scholar 

  20. Cunningham D, Humblet Y, Siena S, Khayat D, Bleiberg H, Santoro A, et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med. 2004;351:337–45. doi:10.1056/NEJMoa033025.

    Article  PubMed  CAS  Google Scholar 

  21. Kwon HC, Oh SY, Lee S, Kim SH, Kim HJ. Bevacizumab plus infusional 5-fluorouracil, leucovorin and irinotecan for advanced colorectal cancer that progressed after oxaliplatin and irinotecan chemotherapy: A pilot study. World J Gastroenterol. 2007;13:6231–5. doi:10.3748/wjg.13.6231.

    Article  PubMed  CAS  Google Scholar 

  22. Chen HX, Mooney M, Boron M, Vena D, Mosby K, Grochow L, et al. Phase II multicenter trial of bevacizumab plus fluorouracil and leucovorin in patients with advanced refractory colorectal cancer: an NCI Treatment Referral Center Trial TRC-0301. J Clin Oncol. 2006;24:3354–60. doi:10.1200/JCO.2005.05.1573.

    Article  PubMed  CAS  Google Scholar 

  23. Jain RK. Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science. 2005;307:58–62. doi:10.1126/science.1104819.

    Article  PubMed  CAS  Google Scholar 

  24. Burstein HJ, Spigel D, Kindsvogel K, Parker LM, Bunnell CA, Partridge AH, et al. Metronomic chemotherapy with and without bevacizumab for advanced breast cancer: a randomized phase II study. Brest Cancer Res Treat. 2005;94 Suppl 1:A4.

    Google Scholar 

  25. Kabbinavar FF, Schulz J, McCleod M, Patel T, Hamm JT, Hecht JR, et al. Addition of bevacizumab to bolus fluorouracil and leucovorin in first-line metastatic colorectal cancer: results of a randomized phase II trial. J Clin Oncol. 2005;23:3697–705. doi:10.1200/JCO.2005.05.112.

    Article  PubMed  CAS  Google Scholar 

  26. Jeung HC, Rha SY, Cho BC, Yoo NC, Roh JK, Roh WJ, et al. A phase II trial of S-1 monotherapy in metastatic colorectal cancer after failure of irinotecan- and oxaliplatin-containing regimens. Br J Cancer. 2006;95:1637–41. doi:10.1038/sj.bjc.6603468.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgment

This study was also supported by a grant of the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (A062254).

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Authors and Affiliations

  1. Section of Oncology, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, 138-736, Korea

    Byung Woog Kang, Tae Won Kim, Jae-Lyun Lee, Min-Hee Ryu, Heung Moon Chang, Yoon-Koo Kang & Jung Shin Lee

  2. Department of General Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, 138-736, Korea

    Chang Sik Yu & Jin Cheon Kim

  3. Department of Radiation Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, 138-736, Korea

    Jong Hoon Kim

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  1. Byung Woog Kang
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Correspondence to Tae Won Kim.

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Kang, B.W., Kim, T.W., Lee, JL. et al. Bevacizumab plus FOLFIRI or FOLFOX as third-line or later treatment in patients with metastatic colorectal cancer after failure of 5-fluorouracil, irinotecan, and oxaliplatin: a retrospective analysis. Med Oncol 26, 32–37 (2009). https://doi.org/10.1007/s12032-008-9077-8

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  • DOI: https://doi.org/10.1007/s12032-008-9077-8

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