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Efficacy of bevacizumab-containing chemotherapy for non-squamous non-small cell lung cancer with bone metastases

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Abstract

Purpose

Skeletal-related events (SREs) negatively affect the quality of life of patients with cancer. Vascular endothelial growth factor receptor (VEGFR)-targeted therapy is effective against bone metastasis in animal models, but the clinical efficacy of anti-VEGFR inhibitors against bone metastases remains unclear. Therefore, we aimed to investigate the efficacy of chemotherapy with bevacizumab, an anti-VEGF antibody, against bone metastases.

Methods

We retrospectively reviewed consecutive patients with non-squamous non-small cell lung cancer who received first-line platinum-based chemotherapy with zoledronic acid at Shizuoka Cancer Center between 2007 and 2011.

Results

Of 25 patients, 13 received bevacizumab-based chemotherapy (BEV group) and 12 received chemotherapy without bevacizumab (non-BEV group). The overall response (54 vs. 8 %, p = 0.01) and disease control (100 vs. 50 %, p = 0.01) rates were higher in the BEV group than in the non-BEV group. The bone-specific response (23 vs. 0 %, p = 0.038) and disease control (100 vs. 67 %, p = 0.01) rates were also higher in the BEV group. The median time to progression (TTP) for bone metastases was higher in the BEV group (13.7 vs. 4.3 months, p = 0.06), whereas that for overall disease was similar between the groups (5.7 vs. 2.6 months, p = 0.17). The proportions of patients with SREs were 23 and 50 % in the BEV and non-BEV groups, respectively (p = 0.16).

Conclusion

Bevacizumab might potentiate the antitumor activity of chemotherapy against systemic disease and bone metastases, prolonging bone-specific TTP and reducing the incidence of SRE.

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References

  1. Coleman RE (1997) Skeletal complications of malignancy. Cancer 80:1588–1594

    Article  PubMed  CAS  Google Scholar 

  2. Kosteva J, Langer CJ (2004) Incidence and distribution of skeletal metastases in NSCLC in the era of PET. Lung Cancer 46 (Suppl 1):S45 (abstract)

    Google Scholar 

  3. Coleman RE (2004) Bisphosphonates: clinical experience. Oncologist 9(suppl 4):14–27

    Article  PubMed  CAS  Google Scholar 

  4. Vogel CL, Yanagihara RH, Wood AJ et al (2004) Safety and pain palliation of zoledronic acid in patients with breast cancer, prostate cancer, or multiple myeloma who previously received bisphosphonate therapy. Oncologist 9:687–695

    Article  PubMed  CAS  Google Scholar 

  5. Coleman RE (2001) Metastatic bone disease: clinical features, pathophysiology and treatment strategies. Cancer Treat Rev 27:165–176

    Article  PubMed  CAS  Google Scholar 

  6. Cook RJ, Major P (2001) Methodology for treatment evaluation in patients with cancer metastatic to bone. J Natl Cancer Inst 93:534–538

    Article  PubMed  CAS  Google Scholar 

  7. Kosteva J, Langer C (2008) The changing landscape of the medical management of skeletal metastases in nonsmall cell lung cancer. Curr Opin Oncol 20:155–161

    Article  PubMed  CAS  Google Scholar 

  8. Weinfurt KP, Li Y, Castel LD et al (2005) The significance of skeletal-related events for the health related quality of life of patients with metastatic prostate cancer. Ann Oncol 16:579–584

    Article  PubMed  CAS  Google Scholar 

  9. Tsuya A, Kurata T, Tamura K, Fukuoka M (2007) Skeletal metastases in non-small cell lung cancer: a retrospective study. Lung Cancer 57:229–232

    Article  PubMed  Google Scholar 

  10. Rosen LS, Gordon D, Tchekmedyian NS et al (2003) Zoledronic acid versus placebo in the treatment of skeletal metastases in patients with lung cancer and other solid tumors: a phase III, double-blind, randomized trial—the Zoledronic Acid Lung Cancer and Other Solid Tumors Study Group. J Clin Oncol 21:3150–3157

    Article  PubMed  CAS  Google Scholar 

  11. Henry DH, Costa L, Goldwasser F et al (2011) Randomized, double-blind study of denosumab versus zoledronic acid in the treatment of bone metastases in patients with advanced cancer (excluding breast and prostate cancer) or multiple myeloma. J Clin Oncol 29:1125–1132

    Article  PubMed  CAS  Google Scholar 

  12. 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  PubMed  CAS  Google Scholar 

  13. Reck M, 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  PubMed  CAS  Google Scholar 

  14. Niho S, Kunitoh H, Nokihara H et al (2012) Randomized phase II study of first-line carboplatin-paclitaxel with or without bevacizumab in Japanese patients with advanced non-squamous non-small-cell lung cancer. Lung Cancer. doi:10.1016/j.lungcan.2011.12.005

    Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  16. Nagengast WB, Vries EG, Hospers GA et al (2007) In vivo VEGF imaging with radiolabeled bevacizumab in a human ovarian tumor xenograft. J Nucl Med 48:1313–1319

    Article  PubMed  CAS  Google Scholar 

  17. Bäuerle T, Hilbig H, Bartling S et al (2008) Bevacizumab inhibits breast cancer-induced osteolysis surrounding soft tissue metastasis, and angiogenesis in rats as visualized by VCT and MRI. Neoplasia 10:511–520

    PubMed  Google Scholar 

  18. Yano S, Muguruma H, Matsumori Y et al (2005) Antitumor vascular strategy for controlling experimental metastatic spread of human small cell lung cancer cells with ZD6474 in natural killer cell-depleted severe combined immunodeficiency mice. Clin Cancer Res 11:8789–8798

    Article  PubMed  CAS  Google Scholar 

  19. Sone S, Yano S (2007) Molecular pathogenesis and its therapeutic modalities of lung cancer metastasis to bone. Cancer Metastasis Rev 26:685–689

    Article  PubMed  CAS  Google Scholar 

  20. Eisenhauer EA, Therasse P, Bogaerts J et al (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45:228–247

    Article  PubMed  CAS  Google Scholar 

  21. Rosen LS, Gordon D, Tchekmedyian NS et al (2003) Long-term efficacy and safety of zoledronic acid in the treatment of skeletal metastases in patients with nonsmall cell lung carcinoma and other solid tumors a randomized, phase III, double-blind, placebo-controlled trial. Cancer 12:2613–2621

    Google Scholar 

  22. Solares SS, Casado DI, Losada MJV, Puyal MT, Pérez AIF, Pajares I (2009) Dramatic complete response in patient with lung adenocarcinoma. Clin Transl Oncol 11:851–853

    Article  Google Scholar 

  23. Paule B, Brion N (2010) Efficacy of sunitinib in patients with renal cell carcinoma with bone metastases. Anticancer Res 30:5165–5168

    PubMed  Google Scholar 

  24. Keizman D, Ish-Shalom M, Pili R et al (2012) Bisphosphonates combined with sunitinib may improve the response rate, progression free survival and overall survival of patients with bone metastases from renal cell carcinoma. Eur J Cancer 48:1031–1037

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The authors thank Scientific Language for reviewing the English manuscript. No financial support was obtained for this study.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Division of Thoracic Oncology, Shizuoka Cancer Center Hospital, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan

    Takaaki Tokito, Takehito Shukuya, Hiroaki Akamatsu, Tetsuhiko Taira, Akira Ono, Hirotsugu Kenmotsu, Tateaki Naito, Haruyasu Murakami, Toshiaki Takahashi & Nobuyuki Yamamoto

  2. Division of Diagnostic Radiology, Shizuoka Cancer Center, Nagaizumi-cho, Sunto-gun, Shizuoka, Japan

    Masahiro Endo

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  1. Takaaki Tokito
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  2. Takehito Shukuya
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  4. Tetsuhiko Taira
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  10. Masahiro Endo
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  11. Nobuyuki Yamamoto
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Correspondence to Takaaki Tokito.

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Tokito, T., Shukuya, T., Akamatsu, H. et al. Efficacy of bevacizumab-containing chemotherapy for non-squamous non-small cell lung cancer with bone metastases. Cancer Chemother Pharmacol 71, 1493–1498 (2013). https://doi.org/10.1007/s00280-013-2148-3

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  • DOI: https://doi.org/10.1007/s00280-013-2148-3

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