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A phase I study of the combination of panitumumab and bevacizumab in KRAS wild-type colorectal cancer patients previously treated with fluoropyrimidine, oxaliplatin, irinotecan and bevacizumab

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Abstract

Purpose

The clinical benefit of combination treatment with panitumumab and bevacizumab (PB) based on bevacizumab beyond progression (BBP) after the failure of second-line chemotherapy remains unclear. We assessed the tolerability and efficacy of PB as BBP in Japanese patients with metastatic colorectal cancer (mCRC).

Methods

This phase I study comprised two parts: (1) PB part to estimate the recommended PB dose, (2) CPB part to investigate the safety of PB with irinotecan (CPB). Three panitumumab doses (4, 5, and 6 mg/kg at Levels −1, 0 and 1, respectively) were set for the PB part, starting with Level 0. Bevacizumab was administered at a fixed dose of 5 mg/kg, regardless of panitumumab dose levels. All drugs were administered on day 1 and repeated every 2 weeks.

Results

No dose-limiting toxicities were observed at Levels 0 (n = 3) and 1 (n = 3) for the PB part, determining the recommended dose as Level 1. During the whole treatment course at Level 1, grade 3 acneiform rash was observed in two patients with a partial response. For six patients (irinotecan biweekly, 150 mg/m2 n = 3, 120 mg/m2 n = 3) enrolled in the CPB part, grade 3 toxicities were leukopenia/neutropenia (n = 1), mucositis (n = 1), diarrhea (n = 1), rash acneiform (n = 1) and thromboembolic event (n = 1), and two of six patients achieved partial responses.

Conclusion

Recommended doses for the PB regimen in mCRC were panitumumab 6 mg/kg and bevacizumab 5 mg/kg. PB and CPB showed manageable toxicities in KRAS wild-type patients previously managed with standard treatment, including bevacizumab.

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Acknowledgments

We gratefully appreciate the participation of patients and their families in this study and would like to thank all co-investigators for their contributions. This study was funded by The Princess Takamatsu Cancer Research.

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Authors and Affiliations

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

    Naoki Takahashi, Satoru Iwasa, Kazuki Sudo, Yusuke Sasaki, Hirokazu Shoji, Yoshitaka Honma, Natsuko Tsuda Okita, Atsuo Takashima, Tetsuya Hamaguchi, Narikazu Boku, Yasuhiro Shimada & Yasuhide Yamada

  2. Multidisciplinary Treatment Cancer Center, Kurume University Hospital, Kurume, Fukuoka, 830-0011, Japan

    Masaru Fukahori

  3. Division of Clinical Oncology, Kochi Health Sciences Center, 2125-1 Ike, Kochi, 781-8555, Japan

    Yasuhiro Shimada

  4. Division of Chemotherapy and Clinical Research, National Cancer Center Research Institute, Tokyo, 104-0045, Japan

    Kazufumi Honda & Tesshi Yamada

Authors
  1. Naoki Takahashi
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  2. Satoru Iwasa
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  3. Masaru Fukahori
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  7. Yoshitaka Honma
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  8. Natsuko Tsuda Okita
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  9. Atsuo Takashima
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  12. Yasuhiro Shimada
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  13. Kazufumi Honda
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  14. Tesshi Yamada
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  15. Yasuhide Yamada
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Corresponding author

Correspondence to Yasuhide Yamada.

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Conflict of interest

Satoru Iwasa has received research funding from Chugai and Daiichi-Sankyo. Tetsuya Hamaguchi has received an honorarium from Chugai. Narikazu Boku has received an honorarium from Yakult. Yasuhiro Shimada has received honorarium from Chugai, Takeda and Daiichi-Sankyo. Tesshi Yamada has received research funding from Carna Bioscience, Inc. All other authors declare that they have no conflict of interest relevant to this study.

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Informed consent was obtained from all individual participants included in the study.

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Takahashi, N., Iwasa, S., Fukahori, M. et al. A phase I study of the combination of panitumumab and bevacizumab in KRAS wild-type colorectal cancer patients previously treated with fluoropyrimidine, oxaliplatin, irinotecan and bevacizumab. Cancer Chemother Pharmacol 78, 567–575 (2016). https://doi.org/10.1007/s00280-016-3111-x

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  • DOI: https://doi.org/10.1007/s00280-016-3111-x

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