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Bevacizumab-associated events in Japanese women with cervical cancer: a multi-institutional survey of Obstetrical Gynecological Society of Kinki district, Japan

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Abstract

Background

The development of perforations or fistulas in the Gastrointestinal (GI) tract or genitourinary (GU) system is a serious adverse effect of bevacizumab. The aim of this study was to investigate the incidences of these GI/GU events as well as their association with previous radiotherapy (RT) in Japanese women with cervical cancer.

Methods

We conducted a written questionnaire survey among 14 gynecological institutions belonging to the Oncology Research Committee of the Obstetrical and Gynecological Society of Kinki District, Japan. The severity of GI/GU events was classified according to the National Cancer Institute’s Common Terminology Criteria for Adverse Events version 5.0. All data were extracted from survey responses and maintained in an Excel spreadsheet and summarized using descriptive statistics.

Results

The information of 224 Japanese women with cervical cancer (152 recurrent and 72 advanced) who were treated with bevacizumab-containing chemotherapy was collected from 14 institutions. Of these, 65% had been previously treated with RT. GI/GU events of any grade developed in 25 (11.2%) patients, leading directly to death in 3 (1.3%) patients. When compared, the incidence of GI/GU events was higher in recurrent disease patients than in advanced disease patients (13.8% vs 5.6%, p = 0.0728). When examined according to the history of RT, the incidence of GI/GU events was greater in patients with a history of RT than in those without (14.5% vs 5.1%, p = 0.044).

Conclusion

More than 10% of patients experience GI/GU events during or after receiving bevacizumab-containing chemotherapies. Prior RT is a risk factor for bevacizumab-associated GI/GU events.

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References

  1. Leath CA 3rd, Straughn JM Jr (2013) Chemotherapy for advanced and recurrent cervical carcinoma: results from cooperative group trials. Gynecol Oncol 129:251–257

    Article  CAS  Google Scholar 

  2. Tewari KS, Sill MW, Long HJ 3rd et al (2014) Improved survival with bevacizumab in advanced cervical cancer. N Engl J Med 370:734–743

    Article  CAS  Google Scholar 

  3. Ferrara N, Gerber HP, LeCouter J (2003) The biology of VEGF and its receptors. Nat Med 9:669–676

    Article  CAS  Google Scholar 

  4. Hurwitz H, Fehrenbacher L, Novotny W et al (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350:2335–2342

    Article  CAS  Google Scholar 

  5. Tewari KS, Sill MW, Penson RT et al (2017) Bevacizumab for advanced cervical cancer: final overall survival and adverse event analysis of a randomised, controlled, open-label, phase 3 trial (Gynecologic Oncology Group 240). Lancet 390:1654–1663

    Article  CAS  Google Scholar 

  6. Komiyama S, Kato K, Inokuchi Y et al (2019) Bevacizumab combined with platinum-taxane chemotherapy as first-line treatment for advanced ovarian cancer: a prospective observational study of safety and efficacy in Japanese patients (JGOG3022 trial). Int J Clin Oncol 24:103–114

    Article  CAS  Google Scholar 

  7. Lordick F, Geinitz H, Theisen J et al (2006) Increased risk of ischemic bowel complications during treatment with bevacizumab after pelvic irradiation: report of three cases. Int J Radiat Oncol Biol Phys 64:1295–1298

    Article  CAS  Google Scholar 

  8. Hapani S, Chu D, Wu S (2009) Risk of gastrointestinal perforation in patients with cancer treated with bevacizumab: a meta-analysis. Lancet Oncol 10:559–568

    Article  CAS  Google Scholar 

  9. Qi WX, Shen Z, Tang LN et al (2014) Bevacizumab increases the risk of gastrointestinal perforation in cancer patients: a meta-analysis with a focus on different subgroups. Eur J Clin Pharmacol 70:893–906

    Article  CAS  Google Scholar 

  10. Fujii Y, Hirahara N, Kaji S et al (2018) Bevacizumab-induced intestinal perforation in a patient with inoperable breast cancer: a case report and review of the literature. J Med Case Rep 12:84

    Article  Google Scholar 

  11. Fujino S, Miyoshi N, Ohue M et al (2015) Use of Vacuum-assisted closure in management of open abdominal wound with multiple enterocutaneous fistulae during chemotherapy: a case report. Int J Surg Case Rep 17:112–116

    Article  Google Scholar 

  12. Kabbinavar FF, Flynn PJ, Kozloff M et al (2012) Gastrointestinal perforation associated with bevacizumab use in metastatic colorectal cancer: results from a large treatment observational cohort study. Eur J Cancer 48:1126–1132

    Article  CAS  Google Scholar 

  13. Miller K, Wang M, Gralow J et al (2007) Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med 357:2666–2676

    Article  CAS  Google Scholar 

  14. Miles DW, Chan A, Dirix LY et al (2010) Phase III study of bevacizumab plus docetaxel compared with placebo plus docetaxel for the first-line treatment of human epidermal growth factor receptor 2–negative metastatic breast cancer. J Clin Oncol 28:3239–3247

    Article  CAS  Google Scholar 

  15. Robert NJ, Diéras V, Glaspy J et al (2011) RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2–negative, locally recurrent or metastatic breast cancer. J Clin Oncol 29:1252–1260

    Article  CAS  Google Scholar 

  16. Chinot OL, Wick W, Mason W et al (2014) Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. N Engl J Med 370:709–722

    Article  CAS  Google Scholar 

  17. Sandler A, Gray R, Perry MC et al (2006) Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 355:2542–2550

    Article  CAS  Google Scholar 

  18. Reck M, von Pawel J, Zatloukal P et al (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 27:1227–1234

    Article  CAS  Google Scholar 

  19. Reck M, von Pawel J, Zatloukal P et al (2010) Overall survival with cisplatin-gemcitabine and bevacizumab or placebo as first-line therapy for nonsquamous non-small-cell lung cancer: results from a randomised phase III trial (AVAiL). Ann Oncol 21:1804–1809

    Article  CAS  Google Scholar 

  20. Socinski MA, Jotte RM, Cappuzzo F et al (2018) Atezolizumab for first-line treatment of metastatic nonsquamous NSCLC. N Engl J Med 378:2288–2301

    Article  CAS  Google Scholar 

  21. Saito H, Fukuhara T, Furuya N et al (2019) Erlotinib plus bevacizumab versus erlotinib alone in patients with EGFR-positive advanced non-squamous non-small-cell lung cancer (NEJ026): interim analysis of an open-label, randomised, multicentre, phase 3 trial. Lancet Oncol 20:625–635

    Article  CAS  Google Scholar 

  22. Ohtsu A, Shah MA, Van Cutsem E et al (2011) Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled phase III study. J Clin Oncol 29:3968–3976

    Article  CAS  Google Scholar 

  23. Finn RS, Qin S, Ikeda M et al (2020) Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med 382:1894–1905

    Article  CAS  Google Scholar 

  24. Burger RA, Brady MF, Bookman MA et al (2011) Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med 365:2473–2483

    Article  CAS  Google Scholar 

  25. Perren TJ, Swart AM, Pfisterer J et al (2011) A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med 365:2484–2496

    Article  CAS  Google Scholar 

  26. Aghajanian C, Blank SV, Goff BA et al (2012) OCEANS: a randomized, double-blind, placebo-controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. J Clin Oncol 30:2039–2045

    Article  CAS  Google Scholar 

  27. Pujade-Lauraine E, Hilpert F, Weber B et al (2014) Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: the AURELIA open-label randomized phase III trial. J Clin Oncol 32:1302–1308

    Article  CAS  Google Scholar 

  28. Coleman RL, Brady MF, Herzog TJ et al (2017) Bevacizumab and paclitaxel-carboplatin chemotherapy and secondary cytoreduction in recurrent, platinum-sensitive ovarian cancer (NRG Oncology/Gynecologic Oncology Group study GOG-0213): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol 18:779–791

    Article  CAS  Google Scholar 

  29. Oza AM, Selle F, Davidenko I et al (2017) Efficacy and safety of bevacizumab-containing therapy in newly diagnosed ovarian cancer: ROSiA single-arm phase 3B study. Int J Gynecol Cancer 27:50–58

    Article  Google Scholar 

  30. Jain RK (2001) Normalizing tumor vasculature with anti-angiogenic therapy: a new paradigm for combination therapy. Nat Med 7:987–989

    Article  CAS  Google Scholar 

  31. Kabbinavar F, Hurwitz HI, Fehrenbacher L et al (2003) Phase II, randomized trial comparing bevacizumab plus fluorouracil (FU)/leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer. J Clin Oncol 21:60–65

    Article  CAS  Google Scholar 

  32. Kabbinavar FF, Hambleton J, Mass RD et al (2005) Combined analysis of efficacy: the addition of bevacizumab to fluorouracil/leucovorin improves survival for patients with metastatic colorectal cancer. J Clin Oncol 23:3706–3712

    Article  CAS  Google Scholar 

  33. Giantonio BJ, Catalano PJ, Meropol NJ et al (2007) Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200. J Clin Oncol 25:1539–1544

    Article  CAS  Google Scholar 

  34. Kamba T, McDonald DM (2007) Mechanisms of adverse effects of anti-VEGF therapy for cancer. Br J Cancer 96:1788–1795

    Article  CAS  Google Scholar 

  35. Rosati G, Avallone A, Aprile G et al (2013) XELOX and bevacizumab followed by single-agent bevacizumab as maintenance therapy as first-line treatment in elderly patients with advanced colorectal cancer: the boxe study. Cancer Chemother Pharmacol 71:257–264

    Article  CAS  Google Scholar 

  36. Saif MW, Elfiky A, Salem RR (2007) Gastrointestinal perforation due to bevacizumab in colorectal cancer. Ann Surg Oncol 14:1860–1869

    Article  Google Scholar 

  37. Zheng Y, Gao W, Spratt DE et al (2020) Management of gastrointestinal perforation related to radiation. Int J Clin Oncol 25:1010–1015

    Article  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan

    Seiji Mabuchi & Sho Matsubara

  2. Department of Obstetrics and Gynecology, Osaka University, Suita, Osaka, Japan

    Misa Yamamoto

  3. Department of Gynecologic Oncology, Osaka International Cancer Institute, Osaka, Osaka, Japan

    Hiroko Murata

  4. Department of Obstetrics and Gynecology, Kansai Medical University, Hirakata, Osaka, Japan

    Takuya Yokoe

  5. Department of Obstetrics and Gynecology, Kyoto University, Kyoto, Kyoto, Japan

    Junzo Hamanishi

  6. Department of Obstetrics and Gynecology, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan

    Yoshito Terai

  7. Department of Obstetrics and Gynecology, Kobe City Medical Center General Hospital, Kobe, Hyogo, Japan

    Hikaru Imatake

  8. Department of Obstetrics and Gynecology, Wakayama Medical University, Wakayama, Wakayama, Japan

    Yasushi Mabuchi

  9. Department of Obstetrics and Gynecology, Kyoto Prefectural University of Medicine, Kyoto, Kyoto, Japan

    Taisuke Mori

  10. Department of Obstetrics and Gynecology, Suita Tokusyukai Hospital, Suita, Osaka, Japan

    Fuminori Kitada

  11. Department of Obstetrics and Gynecology, Nara Prefecture General Medical Center, Nara, Nara, Japan

    Yasuhiro Hashiguchi

  12. Department of Obstetrics and Gynecology, Shiga University of Medical Science, Otsu, Shiga, Japan

    Akimasa Takahashi

  13. Department of Obstetrics and Gynecology, Osaka Medical College, Takatsuki, Osaka, Japan

    Satoe Fujiwara

  14. Department of Obstetrics and Gynecology, Kaizuka City Hospital, Kaizuka, Osaka, Japan

    Hirokazu Naoi

Authors
  1. Seiji Mabuchi
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  2. Misa Yamamoto
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Correspondence to Seiji Mabuchi.

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Mabuchi, S., Yamamoto, M., Murata, H. et al. Bevacizumab-associated events in Japanese women with cervical cancer: a multi-institutional survey of Obstetrical Gynecological Society of Kinki district, Japan. Int J Clin Oncol 26, 598–605 (2021). https://doi.org/10.1007/s10147-020-01826-3

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