Investigational New Drugs

, Volume 36, Issue 4, pp 696–701 | Cite as

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

  • Motohiro Tamiya
  • Hidekazu Suzuki
  • Takayuki Shiroyama
  • Ayako Tanaka
  • Naoko Morishita
  • Norio Okamoto
  • Kenichi Sakai
  • Hironori Shigeoka
  • Kunimitsu Kawahara
  • Tomonori Hirashima


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.


Bevacizumab Intestinal perforation NSCLC Prediction markers 



The authors thank all the participants of this study.


The authors did not receive any funding for this study.

Compliance with ethical standards

Conflict of interest

The authors declare no conflicts of interest.

Ethical approval

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.

Informed consent

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


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Motohiro Tamiya
    • 1
  • Hidekazu Suzuki
    • 2
  • Takayuki Shiroyama
    • 2
  • Ayako Tanaka
    • 2
  • Naoko Morishita
    • 2
  • Norio Okamoto
    • 2
  • Kenichi Sakai
    • 3
  • Hironori Shigeoka
    • 4
  • Kunimitsu Kawahara
    • 5
  • Tomonori Hirashima
    • 2
  1. 1.Department of Thoracic OncologyOsaka International Cancer InstituteOsakaJapan
  2. 2.Department of Thoracic MalignancyOsaka Habikino Medical CenterHabikinoJapan
  3. 3.Department of SurgeryOsaka Gyoumeikan HospitalOsakaJapan
  4. 4.Department of Emergency & Critical Care MedicineKindai University Faculty of MedicineOsakaJapan
  5. 5.Department of PathologyOsaka Habikino Medical CenterHabikinoJapan

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