Skip to main content

Advertisement

SpringerLink
Log in

Bevacizumab in combination with irinotecan, 5-fluorouracil, and leucovorin (FOLFIRI) in patients with metastatic colorectal cancer who were previously treated with oxaliplatin-containing regimens: a multicenter observational cohort study (TCTG 2nd-BV study)

  • Original Paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

The efficacy of bevacizumab combined with infusional 5-fluorouracil/leucovorin (5-FU/LV) plus irinotecan (FOLFIRI) as the second-line treatment for metastatic colorectal cancer (mCRC) has not been fully clarified, although bevacizumab combined with infusional 5-FU/LV plus oxaliplatin (FOLFOX) in the second-line setting has demonstrated a survival benefit. We investigated the efficacy of bevacizumab plus FOLFIRI in mCRC patients who failed oxaliplatin-containing regimens without bevacizumab. Patients who received bevacizumab plus FOLFIRI or bevacizumab plus FOLFOX as second-line chemotherapy between July 2007 and March 2008 were registered (trial registration: UMIN000001547). Patient background data and progression-free survival (PFS), overall survival (OS), response, and bevacizumab-related adverse events were prospectively collected every 6 months. A total of 195 patients were enrolled from 26 institutions. Among them, 115 patients received bevacizumab plus FOLFIRI after failure of oxaliplatin and fluoropyrimidine (FOLFIRI+BV after OX/FU group), and 45 patients received bevacizumab plus FOLFOX after failure of irinotecan and fluoropyrimidine (FOLFOX+BV after IRI/FU group). Median PFS was 8.3 months (95% confidence interval [CI], 6.7–9.9) for the FOLFIRI+BV after OX/FU group and 7.8 months (95% CI, 5.8–9.7) for the FOLFOX+BV after IRI/FU group. Median OS was 21.6 months (95% CI, 17.6–25.6) and 16.5 months (95% CI, 11.8–21.2), respectively. Overall response rates were 25 and 29%, respectively. The most common grade ≥3 bevacizumab-related adverse events were hypertension (5.0%) and bleeding (3.8%). FOLFIRI+BV after OX/FU showed comparable efficacy to FOLFOX+BV after IRI/FU.

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

Abbreviations

5-FU/LV:

5-Flurouracil/leucovorin

FOLFIRI:

Infusional 5-fluorouracil/leucovorin plus irinotecan

FOLFOX:

Infusional 5-fluorouracil/leucovorin plus oxaliplatin

mCRC:

Metastatic colorectal cancer

PFS:

Progression-free survival

OS:

Overall survival

TCTG:

Tsukuba Cancer Clinical Trial Group

ECOG:

Eastern Cooperative Oncology Group

PS:

Performance status

UMIN:

University Hospital Medical Information Network

EGFR:

Epidermal growth factor receptor

CI:

Confidence interval

FOLFIRI+BV after OX/FU group:

Patients who received bevacizumab plus FOLFIRI after failure of oxaliplatin and fluoropyrimidine

FOLFOX+BV after IRI/FU group:

Patients who received bevacizumab plus FOLFOX after failure of irinotecan and fluoropyrimidine

FLOX:

Bolus 5-fluorouracil/leucovorin plus oxaliplatin

XELOX:

Capecitabine plus oxaliplatin

References

  1. 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  PubMed  CAS  Google Scholar 

  2. Sobrero A, Ackland S, Clarke S, et al. Phase IV study of bevacizumab in combination with infusional fluorouracil, leucovorin and irinotecan (FOLFIRI) in first-line metastatic colorectal cancer. Oncology. 2009;77:113–9.

    Article  PubMed  CAS  Google Scholar 

  3. 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  PubMed  CAS  Google Scholar 

  4. 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  PubMed  CAS  Google Scholar 

  5. 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  PubMed  CAS  Google Scholar 

  6. Giantonio BJ, Catalano PJ, Meropol NJ, 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.

    Article  PubMed  CAS  Google Scholar 

  7. ETHICAL guidelines for epidemiological research. http://www.niph.go.jp/wadai/ekigakurinri/guidelines.pdf.

  8. 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.

    Article  PubMed  CAS  Google Scholar 

  9. 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.

    Article  PubMed  CAS  Google Scholar 

  10. Andre T, Boni C, Mounedji-Boudiaf L, et al. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med. 2004;350:2343–51.

    Article  PubMed  CAS  Google Scholar 

  11. Peeters M, Price TJ, Cervantes A, et al. Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer. J Clin Oncol. 2010;28:4706–13.

    Article  PubMed  CAS  Google Scholar 

  12. 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  PubMed  CAS  Google Scholar 

  13. 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  PubMed  CAS  Google Scholar 

  14. Yildiz R, Buyukberber S, Uner A, et al. Bevacizumab plus irinotecan-based therapy in metastatic colorectal cancer patients previously treated with oxaliplatin-based regimens. Cancer Invest. 2010;28:33–7.

    Article  PubMed  CAS  Google Scholar 

  15. Van Cutsem E, Rivera F, Berry S, et al. Safety and efficacy of first-line bevacizumab with FOLFOX, XELOX, FOLFIRI and fluoropyrimidines in metastatic colorectal cancer: the BEAT study. Ann Oncol. 2009;20:1842–7.

    Article  PubMed  Google Scholar 

  16. Kozloff M, Yood MU, Berlin J, et al. Clinical outcomes associated with bevacizumab-containing treatment of metastatic colorectal cancer: the BRiTE observational cohort study. Oncologist. 2009;14:862–70.

    Article  PubMed  CAS  Google Scholar 

  17. Bekaii-Saab TS, Bendell JC, Cohn AL, et al. Bevacizumab (BV) plus chemotherapy (CT) in second-line metastatic colorectal cancer (mCRC): Initial results from ARIES, a second BV observational cohort study (OCS). J Clin Oncol 2010;28:15s (suppl; abstr 3495).

    Google Scholar 

Download references

Acknowledgments

The authors would like to thank all of the investigators at the 26 institutions and the patients who participated in this study. Study investigators: Chiba Cancer Center: T. Denda; Dongo Hospital: M. Matsuoka; Hokkaido University Hospital: Y. Komatsu, I. Iwanaga; Ibaraki Prefectural Central Hospital and Cancer Center: K. Amagai, M. Ozeki; Iwate prefectural Central Hospital: S. Kato; Kanagawa Cancer Center: S. Motomura, C. Hashimoto; Kinki University School of Medicine: T. Satoh, S. Fumita; Kitazato University East Hospital: W. Koizumi, T. Sasaki; Kobe University Hospital: T. Okuno, Y. Fujishima; Kushiro City General Hospital: T. Abe; Kyushu University Hospital: E. Baba; Minoh City Hospital: K. Kato, Y. Miyake; Mito Medical Center: T. Yamaguchi, S. Yoshida; Nagoya Memorial Hospital: K. Ina, R. Furuta; National Cancer Center Hospital: H. Yamada, A. Takashima; National Cancer Center Hospital East: T. Yoshino, H. Bando; National Kyushu Cancer Center: T. Esaki, M. Ohta; Osaka City General Hospital: S. Tokunaga, M. Hattori; Ritsurin Hospital: S. Indo, A. Teramoto; Saitama Medical University International Medical Center: K. Yamashita; Sakai Municipal Hospital: M. Fukunaga, H. Takemoto; Shikoku Cancer Center: T. Nishina, T. Kajiwara; Shizuoka Cancer Center: K. Yamazaki; Suita Municipal Hospital: K. Murata, S. Tanaka; Tokyo Medical University: K. Katsumata, Y. Mori; Tsukuba University Hospital: I. Hyodo, T. Moriwaki. This work was supported by the NPO Tsukuba Cancer Clinical Trial Group (TCTG). Portions of this study data have been previously presented at the 35th European Society for Medical Oncology Congress in 2010.

Conflict of interest

Dr. Hyodo received funds in an advisory role from Yakult Honsha and Chugai Pharmaceuticals. All other authors state that they have no conflicts of interest.

Author information

Authors and Affiliations

  1. Division of Gastroenterology, Tsukuba University Hospital, Tennodai 1-1-1, Tsukuba, 305-8575, Ibaraki, Japan

    Toshikazu Moriwaki & Ichinosuke Hyodo

  2. Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan

    Hideaki Bando

  3. Gastrointestinal Oncology Division, National Cancer Center Hospital, Tokyo, Japan

    Atsuo Takashima

  4. Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan

    Kentaro Yamazaki

  5. Gastrointestinal and Medical Oncology Division, National Kyushu Cancer Center, Fukuoka, Japan

    Taito Esaki

  6. Department of Medical Oncology, Saitama Medical University, Hidaka, Japan

    Keishi Yamashita

  7. Department of Surgery, Sakai Municipal Hospital, Sakai, Japan

    Mutsumi Fukunaga

  8. Department of Surgery, Minoh City Hospital, Minoh, Japan

    Yasuhiro Miyake

  9. Department of Surgery, Tokyo Medical University, Tokyo, Japan

    Kenji Katsumata

  10. Department of Medical Oncology, Iwate Prefectural Central Hospital, Iwate, Japan

    Satoshi Kato

  11. Department of Medical Oncology, Faculty of Medicine, Kinki University, Osaka, Japan

    Taroh Satoh

  12. Division of Gastroenterology, Ibaraki Prefectural Central Hospital and Cancer Center, Kasama, Japan

    Mitsuharu Ozeki

  13. Department of Hematology and Oncology, Kyushu University Hospital, Fukuoka, Japan

    Eishi Baba

  14. Department of Gastroenterology, Mito Medical Center, Higashi Ibaraki-gun, Japan

    Shigemasa Yoshida

  15. Department of Clinical Oncology, St. Marianna University, Kawasaki, Japan

    Narikazu Boku

Authors
  1. Toshikazu Moriwaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hideaki Bando
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Atsuo Takashima
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kentaro Yamazaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Taito Esaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Keishi Yamashita
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mutsumi Fukunaga
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yasuhiro Miyake
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Kenji Katsumata
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Satoshi Kato
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Taroh Satoh
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Mitsuharu Ozeki
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Eishi Baba
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Shigemasa Yoshida
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Narikazu Boku
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Ichinosuke Hyodo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Toshikazu Moriwaki.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Moriwaki, T., Bando, H., Takashima, A. et al. Bevacizumab in combination with irinotecan, 5-fluorouracil, and leucovorin (FOLFIRI) in patients with metastatic colorectal cancer who were previously treated with oxaliplatin-containing regimens: a multicenter observational cohort study (TCTG 2nd-BV study). Med Oncol 29, 2842–2848 (2012). https://doi.org/10.1007/s12032-011-0151-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12032-011-0151-2

Keywords

Search

Navigation