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Neoadjuvant capecitabine and oxaliplatin (XELOX) combined with bevacizumab for high-risk localized rectal cancer

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Abstract

Purpose

Chemoradiotherapy followed by total mesorectal excision (TME) is the standard treatment for locally advanced rectal cancer. Although this approach decreases the risk of local recurrence, pelvic radiation is associated with long-term morbidity and delays systemic treatment. We conducted this study to evaluate the feasibility of neoadjuvant capecitabine and oxaliplatin (XELOX) plus bevacizumab as a treatment for high-risk localized rectal cancer.

Methods

Patients with T4 or lymph node-positive rectal cancer were treated with three cycles of XELOX plus bevacizumab and one additional cycle of XELOX. This was followed by TME performed 3–8 weeks after the last chemotherapy session.

Results

Twenty-five patients were recruited between December 2009 and November 2011. In seven of the patients (28.0 %), grade 3–4 adverse events occurred. After preoperative chemotherapy, the frequency of tumor (T) downstaging was 69.6 %, and that of lymph node (N) downstaging was 78.9 %. Seven patients discontinued the treatment after 2–3 cycles of XELOX plus bevacizumab. The frequency of subsequent surgery was 92 %, and all patients underwent R0 resections. Postoperative complications occurred in six patients (26.1 %). One patient achieved a pathological complete response (pCR) for the primary tumor and lymph nodes, whereas an additional four patients achieved near-pCR. After a median follow-up of 31 months, five patients displayed metastatic progression, including one who suffered local recurrence.

Conclusions

XELOX plus bevacizumab followed by TME is feasible for high-risk localized rectal cancer, as it achieves good tumor regression and causes manageable toxicity.

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Acknowledgments

We are indebted to Fumikazu Koyama of the Department of Surgery, Nara Medical University and Kiyoshi Maeda of the Department of Surgical Oncology, Osaka City University Graduate School of Medicine, for serving on the study’s safety and efficacy committee. We thank Yuko Ohno and Megumi Hori of the Department of Mathematical Health Science, Graduate School of Medicine, Osaka University, for their help with the data management. This study was supported by the Supporting Center for Clinical Research and Education (SCCRE).

Conflict of interest

The authors have no conflict of interest to declare.

Author information

Authors and Affiliations

  1. Clinical Study Group of Osaka University (CSGO), Colorectal Group, Suita, Osaka, Japan

    Junichi Hasegawa, Junichi Nishimura, Tsunekazu Mizushima, Yasuhiro Miyake, Ho Min Kim, Hiroyoshi Takemoto, Hroshi Tamagawa, Shingo Noura, Makoto Fujii, Yujiro Fujie, Takeshi Kato, Ichiro Takemasa, Masataka Ikeda, Hirofumi Yamamoto, Mistugu Sekimoto, Riichiro Nezu, Yuichiro Doki & Masaki Mori

  2. Department of Surgery, Osaka Rosai Hospital, 1179-3 Nagasone, Kita-ku, Sakai, 591-8025, Osaka, Japan

    Junichi Hasegawa, Junichi Nishimura, Ho Min Kim & Riichiro Nezu

  3. Department of Surgery, Osaka University Graduate School of Medicine, 2-15 Yamadaoka, Suita, 565-0871, Osaka, Japan

    Junichi Nishimura, Tsunekazu Mizushima, Ichiro Takemasa, Masataka Ikeda, Hirofumi Yamamoto, Mistugu Sekimoto, Yuichiro Doki & Masaki Mori

  4. Department of Surgery, Minoh City Hospital, 5-7-1 Kayano, Minoh, 562-0014, Osaka, Japan

    Yasuhiro Miyake & Takeshi Kato

  5. Department of Surgery, Nishinomiya Municipal Central Hospital, 8-24 Hayashida, Nishinomiya, 663-8014, Hyogo, Japan

    Yasuhiro Miyake & Riichiro Nezu

  6. Department of Surgery, Sakai City Hospital, 1-1-1 Minami Yasui, Sakai-ku, Sakai, 590-0064, Osaka, Japan

    Hiroyoshi Takemoto

  7. Department of Surgery, Kinki Central Hospital of the Mutual Aid Association of Public School Teachers, 3-1, Kurumazuka, Itami, 664-8533, Hyogo, Japan

    Hiroyoshi Takemoto

  8. Department of Surgery, Osaka General Medical Center, 3-1-56 Mandaihiga-shi, Sumiyoshi-ku, Osaka, 558-0056, Japan

    Hroshi Tamagawa

  9. Department of Surgery, Otemae Hospital, 1-5-34, Otemae, Chuo-ku, Osaka, 540-0008, Japan

    Hroshi Tamagawa

  10. Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Disease, 1-3-3 Nakamichi, Higashinari-ku, Osaka, 537-8511, Japan

    Shingo Noura

  11. Department of Surgery, Osaka Kosei Nenkin Hospital, 4-2-78 Fukushima, Fukushima-ku, Osaka, 553-0003, Japan

    Makoto Fujii

  12. Department of Surgery, Osaka Saiseikai Senri Hospital, 1-1 D-6 Tsukumodai, Suita, 565-0862, Osaka, Japan

    Yujiro Fujie

  13. Department of Surgery, NTT West Osaka Hospital, 2-6-40 Karasugatsuji, Tennoji-ku, Osaka, 543-8922, Japan

    Yujiro Fujie

  14. Department of Surgery, Kansai Rosai Hospital, 3-1-69 Inabaso, Amagasaki, 660-8511, Hyogo, Japan

    Takeshi Kato

  15. Department of Pathology, Osaka Rosai Hospital, 1179-3 Nagasone, Kita-ku, Sakai, 591-8025, Osaka, Japan

    Hideaki Miwa

  16. Department of Surgery, National Hospital Organization, Osaka National Hospital, 2-1-14 Hoenzaka, Chuo-ku, Osaka, 540-0006, Japan

    Masataka Ikeda & Mistugu Sekimoto

Authors
  1. Junichi Hasegawa
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  2. Junichi Nishimura
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  3. Tsunekazu Mizushima
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  4. Yasuhiro Miyake
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  5. Ho Min Kim
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  6. Hiroyoshi Takemoto
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  7. Hroshi Tamagawa
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  8. Shingo Noura
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  9. Makoto Fujii
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  10. Yujiro Fujie
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  11. Takeshi Kato
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  12. Hideaki Miwa
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  13. Ichiro Takemasa
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  14. Masataka Ikeda
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  15. Hirofumi Yamamoto
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  16. Mistugu Sekimoto
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  17. Riichiro Nezu
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  18. Yuichiro Doki
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  19. Masaki Mori
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Corresponding author

Correspondence to Junichi Hasegawa.

Additional information

Junichi Hasegawa and Junichi Nishimura have contributed equally to this work.

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Hasegawa, J., Nishimura, J., Mizushima, T. et al. Neoadjuvant capecitabine and oxaliplatin (XELOX) combined with bevacizumab for high-risk localized rectal cancer. Cancer Chemother Pharmacol 73, 1079–1087 (2014). https://doi.org/10.1007/s00280-014-2417-9

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  • DOI: https://doi.org/10.1007/s00280-014-2417-9

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