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Clinical predictors of bevacizumab-associated intestinal perforation in non-small cell lung cancer

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Summary

Background Bevacizumab (Bev) is generally well-tolerated, and Bev-associated intestinal perforation (BAP) is a rare albeit serious side effect in cases of non-small cell lung cancer (NSCLC). Therefore, the present study aimed to identify clinical predictors of BAP to help predict and manage the development of life-threatening intestinal complications among patients receiving Bev. Methods This retrospective study evaluated demographic, clinical, and treatment factors for patients with NSCLC who were treated with Bev between February 2010 and August 2015 at our center. Results We identified 314 regimens (208 patients; median age: 65 years; 115 women) for analysis, which included 119 first-line regimens, 74 s-line regimens, and 121 third-line or later regimens. BAP occurred in 7 cases (2.23% among all regimens and 3.37% among all patients), which generally occurred during first- or second-line treatment and was caused by ulcerative colitis (1 case), colon diverticulitis (1 case), and idiopathic perforations (5 cases). Univariate analyses revealed that BAP was significantly associated with deteriorating PS during the first cycle of chemotherapy (odd ratio [OR]: 11.07, 95% confidence interval [CI]: 2.37–51.63, p = 0.0022), grade ≥ 3 diarrhea (OR: 11.37, 95% CI: 2.37–54.50, p = 0.0024), febrile neutropenia (OR: 9.16, 95% CI: 1.98–42.49, p = 0.0047), and stomatitis (OR: 4.60, 95% CI: 1.01–21.04, p = 0.0492). Conclusions Among patients with NSCLC, BAP was associated with deteriorating PS during the first cycle of chemotherapy, grade ≥ 3 diarrhea, febrile neutropenia, and stomatitis. Therefore, careful observation is needed for patients with NSCLC who receive Bev in any line of treatment, especially if they develop serious side effects that affect their PS or mucous membrane.

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Acknowledgments

The authors thank all the participants of this study.

Funding

The authors did not receive any funding for this study.

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Authors and Affiliations

  1. Department of Thoracic Oncology, Osaka International Cancer Institute, 3-1-69 Otemachi Chuo-ku, Osaka, 541-8567, Japan

    Motohiro Tamiya

  2. Department of Thoracic Malignancy, Osaka Habikino Medical Center, Habikino, Japan

    Hidekazu Suzuki, Takayuki Shiroyama, Ayako Tanaka, Naoko Morishita, Norio Okamoto & Tomonori Hirashima

  3. Department of Surgery, Osaka Gyoumeikan Hospital, Osaka, Japan

    Kenichi Sakai

  4. Department of Emergency & Critical Care Medicine, Kindai University Faculty of Medicine, Osaka, Japan

    Hironori Shigeoka

  5. Department of Pathology, Osaka Habikino Medical Center, Habikino, Japan

    Kunimitsu Kawahara

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  1. Motohiro Tamiya
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  2. Hidekazu Suzuki
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  3. Takayuki Shiroyama
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  4. Ayako Tanaka
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  5. Naoko Morishita
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Correspondence to Motohiro Tamiya.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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

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Tamiya, M., Suzuki, H., Shiroyama, T. et al. Clinical predictors of bevacizumab-associated intestinal perforation in non-small cell lung cancer. Invest New Drugs 36, 696–701 (2018). https://doi.org/10.1007/s10637-018-0581-1

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