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Bevacizumab plus chemotherapy for advanced non-squamous non-small-cell lung cancer with malignant pleural effusion

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Abstract

Purpose

The presence of malignant pleural effusion (MPE) indicates a poorer prognosis for patients with non-small-cell lung cancer (NSCLC) and impairs their quality of life. Because vascular endothelial growth factor (VEGF) is the key mediator MPE production, we evaluated the efficacy and safety of chemotherapy plus bevacizumab, an anti-VEGF antibody, in non-squamous NSCLC patients with MPE, especially regarding the control of pleural effusions.

Methods

From November 1, 2009 to September 30, 2011, medical charts of 13 consecutive patients with MPE who received bevacizumab plus chemotherapy as the initial or secondary treatment were retrospectively analyzed.

Results

Of the 13 patients, 6 did not undergo pleurodesis, 3 were unsuccessfully treated by pleurodesis, 2 had encapsulated pleural effusion, and 2 had no re-expansion of the lung. Twelve patients (92.3 %) achieved MPE control lasting >8 weeks following bevacizumab plus chemotherapy. Five of 10 patients with measurable lesions had confirmed partial responses. Of 3 patients without measurable lesions, one had confirmed CR. Median progression-free survival time without re-accumulation of MPE was 312 days. Grade 3 or 4 neutropenia, thrombocytopenia, hypertension, or proteinuria was observed in 2, 2, 1, or 1 patient, respectively.

Conclusions

This is the first study to report that bevacizumab plus chemotherapy is highly effective for the management of MPE in non-squamous NSCLC patients. Prospective clinical trials are warranted to investigate the efficacy of bevacizumab for MPE.

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References

  1. Figlin R, Mendoza E, Piantadosi S et al (1994) Intrapleural chemotherapy without pleurodesis for malignant pleural effusions. LCSG Trial 861. Chest 106:S363–S366

    Google Scholar 

  2. Sugiura S, Ando Y, Minami H et al (1997) Prognostic value of pleural effusion in patients with non-small cell lung cancer. Clin Cancer Res 3:47–50

    PubMed  CAS  Google Scholar 

  3. Goodman A, Davies CW (2006) Efficacy of short-term versus long-term chest tube drainage following talc slurry pleurodesis in patients with malignant pleural effusions: a randomized trial. Lung Cancer 54:51–55

    Article  PubMed  Google Scholar 

  4. Stefani A, Natali P, Casali C et al (2006) Talc poudrage versus talc slurry in the treatment of malignant effusion. A prospective comparative study. Eur J Cardiothorac Surg 30:827–832

    Article  PubMed  Google Scholar 

  5. Kolscmann S, Ballin A, Gillissen A (2005) Clinical efficacy and safety of thoracoscopic talc pleurodesis in malignant pleural effusions. Chest 128:1431–1435

    Article  Google Scholar 

  6. Dresler CM, Olack J, Herndon JE II et al (2005) Phaze III intergroup study of talc poudrage versus talc slurry sclerosis for malignant pleural effusion. Chest 127:909–915

    Article  PubMed  Google Scholar 

  7. da Silveira Paschoalini M, Vargas FS, Marchi E et al (2005) Prospective randomized trial of silver nitrate vs talc slurry in pleurodesis for symptomatic malignant pleural effusions. Chest 128:684–689

    Article  Google Scholar 

  8. Sartori S, Tassinari D, Ceccotti P et al (2004) Prospective randomized trial of intrapleural bleomycin versus interferon alfa-2b via ultrasound guided small-bore chest tube in the palliative treatment of malignant pleural effusions. J Clin Oncol 22:1228–1233

    Article  PubMed  CAS  Google Scholar 

  9. Yoshida K, Sugiura T, Takifuji N et al (2007) Randomized phase II trial of three intrapleural therapy regimens for the management of malignant pleural effusion in previously untreated non-small cell lung cancer: JCOG 9515. Lung Cancer 58:362–368

    Article  PubMed  Google Scholar 

  10. Ishimoto O, Saijo Y, Narumi K et al (2002) High level of vascular endothelial growth factor in hemorrhagic pleural effusion of cancer. Oncology 63(1):70–75

    Article  PubMed  CAS  Google Scholar 

  11. Ruiz E, Almán C, Alegre J et al (2005) Angiogenic factors and angiogenesis inhibitors in exudative pleural effusions. Lung 183:185–195

    Article  PubMed  CAS  Google Scholar 

  12. Hamed EA, El-Noweihi AM, Mohamed A et al (2004) Vasoactive mediators (VEGF and TNF-α) in patients with malignant and tuberculous effusions. Respirology 9:81–86

    Article  PubMed  Google Scholar 

  13. Thickett DR, Armstrong L, Millar AB et al (1999) Vascular endothelial growth factor (VEGF) inflammatory and malignant pleural effusions. Thorax 54:707–710

    Article  PubMed  CAS  Google Scholar 

  14. Grove CS, Lee YC (2002) Vascular endothelial growth factor: the key mediator in pleural effusion formation. Curr Opin Pulm Med 8:294–301

    Article  PubMed  Google Scholar 

  15. Brown LF, Detmar M, Claffy K et al (1997) Vascular permeability factor/vascular endothelial growth factor: a multifunctional angiogenic cytokine. EXS 79:233–269

    PubMed  CAS  Google Scholar 

  16. Dvorak HF (2002) Vascular permeability factor/vascular endothelial growth factor: a critical cytokine in tumor angiogenesis and a potential target for diagnosis and therapy. J Clin Oncol 20:4368–4380

    Article  PubMed  CAS  Google Scholar 

  17. Cheng DS, Lee YC, Rodgers JT et al (2000) Vascular endothelial growth factor level correlates with transforming growth factor beta isoform levels in pleural effusions. Chest 118:1747–1753

    Article  PubMed  CAS  Google Scholar 

  18. Cheng DS, Rodriguez RM, Perkett EA et al (1999) Vascular endothelial growth factor in pleural fluid. Chest 116:760–765

    Article  PubMed  CAS  Google Scholar 

  19. Yanagawa H, Takeuchi E, Suzuki Y et al (1999) Vascular endothelial growth factor in malignant pleural effusion associated with lung cancer. Cancer Immunol Immunother 48:396–400

    Article  PubMed  CAS  Google Scholar 

  20. Verheul HMW, Hoekman K, Jorna AS et al (2000) Targeting vascular endothelial growth factor blockade: ascites and pleural effusion formation. Oncologist 5:45–50

    Article  PubMed  CAS  Google Scholar 

  21. Strizzi L, Catalano A, Vianale G et al (2001) Vascular endothelial growth factor is an autocrine growth factor in human malignant mesothelioma. J Pathol 193:468–475

    Article  PubMed  CAS  Google Scholar 

  22. Rebeiro CCS, Vargas FS, Antonangelo L et al (2009) Monoclonal anti-vascular endothelial growth factor antibody reduces fluid volume in an experimental model of inflammatory pleural effusion. Respirology 14:1188–1193

    Article  Google Scholar 

  23. Luo JC, Toyoda M, Shibuya M (1998) Different inhibition of fluid accumulation and tumor growth in two mouse ascites tumors by an antivascular endothelial growth factor/permeability factor neutralizing antibody. Cancer Res 58:2594–2600

    PubMed  CAS  Google Scholar 

  24. Shibuya M, Luo JC, Toyoda M et al (1999) Involvement of VEGF and its receptors in ascites tumor formation. Cancer Chemother Pharmacol 43(suppl):S72–S77

    Article  PubMed  CAS  Google Scholar 

  25. Hu L, Hoffmann J, Zaloudek C et al (2002) Vascular endothelial growth factor immunoneutralization plus paclitaxel markedly reduces tumor burden and ascites in athymic mouse model of ovarian cancer. Am J Pathol 161:1917–1924

    Article  PubMed  CAS  Google Scholar 

  26. Mesiano S, Ferrara N, Jaffe RB et al (1998) Role of vascular endothelial growth factor in ovarian cancer: inhibition of ascites formation by immunoneutralization. Am J Pathol 153:1249–1256

    Article  PubMed  CAS  Google Scholar 

  27. Shaheen RM, Ahmad SA, Liu W et al (2001) Inhibited growth of colon cancer carcinomatosis by antibodies to vascular endothelial and epidermal growth factor receptors. Br J Cancer 85:584–589

    Article  PubMed  CAS  Google Scholar 

  28. Pichelmayer O, Gruenberger B, Zielinski C et al (2006) Bevacizumab is active in malignant effusion. Ann Oncol 17:1853

    Article  PubMed  CAS  Google Scholar 

  29. Numnun TM, Rocconi RP, Whitworth J et al (2006) The use of bevacizumab to palliate symptomatic ascites in patients with refractory ovarian carcinoma. Gynecol Oncol 102:425–428

    Article  Google Scholar 

  30. El-Shami K, Elsaid A, El-kerm Y (2007) Open-label safety and efficacy pilot trial of intraperitoneal bevacizumab as palliative treatment in refractory malignant ascites. J Clin Oncol 205(18 suppl):9043

    Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  32. Reck M, von Pawl 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 

  33. Reck M, von Pawl 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 randomized phase III trial (AVAiL). Ann Oncol 21:1804–1809

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The study was, in part, supported by National Cancer Center Research and Development Fund (23-A-30).

Conflict of interest

Akihiko Gemma has received lecture fees from Chugai Pharmaceutical Company. The other authors indicated no potential conflicts of interest.

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Authors and Affiliations

  1. Division of Pulmonary Medicine, Infection and Oncology, Department of Internal Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan

    Kazuhiro Kitamura, Kaoru Kubota, Satoshi Takahashi, Nobuhiko Nishijima, Teppei Sugano, Masaru Toyokawa, Seiji Kosaihira, Rintaro Noro, Yuji Minegishi, Masahiro Seike, Akinobu Yoshimura & Akihiko Gemma

  2. Department of Internal Medicine, Tsuboi Cancer Center Hospital, 1-10-13 Asakamachi Nagakubo, Koriyama, Fukushima, 963-0197, Japan

    Masahiro Ando & Koji Miwa

Authors
  1. Kazuhiro Kitamura
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  2. Kaoru Kubota
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  14. Akihiko Gemma
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Correspondence to Kaoru Kubota.

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Kitamura, K., Kubota, K., Ando, M. et al. Bevacizumab plus chemotherapy for advanced non-squamous non-small-cell lung cancer with malignant pleural effusion. Cancer Chemother Pharmacol 71, 457–461 (2013). https://doi.org/10.1007/s00280-012-2026-4

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  • DOI: https://doi.org/10.1007/s00280-012-2026-4

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