Clinical predictors of bevacizumab-associated intestinal perforation in non-small cell lung cancer
- 11 Downloads
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.
KeywordsBevacizumab Intestinal perforation NSCLC Prediction markers
The authors thank all the participants of this study.
Compliance with ethical standards
Conflict of interest
The authors declare no conflicts of interest.
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 was obtained from all individual participants included in the study.
- 3.Reck M, von Pawel J, Zatloukal P, Ramlau R, Gorbounova V, Hirsh V, Leighl N, Mezger J, Archer V, Moore N, Manegold C (2009) Phase III trial of cisplatin plus gemcitabine with either placebo or bevacizumab as first-line therapy for nonsquamous non-small-cell lung cancer: AVAil. J Clin Oncol 27:1227–1234CrossRefPubMedGoogle Scholar
- 4.Takeda M, Okamoto I, Yamanaka T, Nakagawa K, Nakanishi Y (2012) Impact of treatment with bevacizumab beyond disease progression: a randomized phase II study of docetaxel with or without bevacizumab after platinum-based chemotherapy plus bevacizumab in patients with advanced nonsquamous non-small cell lung cancer (WJOG 5910L). BMC Cancer 12:327CrossRefPubMedPubMedCentralGoogle Scholar
- 5.Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, Berlin J, Baron A, Griffing S, Holmgren E, Ferrara N, Fyfe G, Rogers B, Ross R, Kabbinavar F (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350:2335–2342CrossRefPubMedGoogle Scholar
- 7.Bennouna J, Sastre J, Arnold D, Österlund P, Greil R, Van Cutsem E, von Moos R, Viéitez JM, Bouché O, Borg C, Steffens CC, Alonso-Orduña V, Schlichting C, Reyes-Rivera I, Bendahmane B, André T, Kubicka S, ML18147 Study Investigators (2013) Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): a randomised phase 3 trial. Lancet Oncol 14:29–37CrossRefPubMedGoogle Scholar
- 13.Burger RA, Brady MF, Bookman MA, Monk BJ, Walker JL, Homesley HD, Fowler J, Greer BE, Boente M, Fleming GF, Lim PC, Rubin SC, Katsumata N, Liang SX (2014) Risk factors for GI adverse events in a phase III randomized trial of bevacizumab in first-line therapy of advanced ovarian cancer: a gynecologic oncology group study. J Clin Oncol 32:1210–1217CrossRefPubMedPubMedCentralGoogle Scholar
- 15.Tamiya M, Tamiya A, Yamadori T, Nakao K, Asami K, Yasue T, Otsuka T, Shiroyama T, Morishita N, Suzuki H, Okamoto N, Okishio K, Kawaguchi T, Atagi S, Kawase I, Hirashima T (2013) Phase2 study of bevacizumab with carboplatin-paclitaxel for non-small cell lung cancer with malignant pleural effusion. Med Oncol 30:676CrossRefPubMedGoogle Scholar
- 16.Kitamura K, Kubota K, Ando M, Takahashi S, Nishijima N, Sugano T, Toyokawa M, Miwa K, Kosaihira S, Noro R, Minegishi Y, Seike M, Yoshimura A, Gemma A (2013) Bevacizumab plus chemotherapy for advanced non-squamous non-small-cell lung cancer with malignant pleural effusion. Cancer Chemother Pharmacol 71:457–461CrossRefPubMedGoogle Scholar
- 26.Kamba T, Tam BY, Hashizume H, Haskell A, Sennino B, Mancuso MR, Norberg SM, O'Brien SM, Davis RB, Gowen LC, Anderson KD, Thurston G, Joho S, Springer ML, Kuo CJ, McDonald DM (2006) VEGF-dependent plasticity of fenestrated capillaries in the normal adult microvasculature. Am J Physiol Heart Circ Physiol 290:H560–H576CrossRefPubMedGoogle Scholar