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Evaluation of toxicity of carmustine with or without bevacizumab in patients with recurrent or progressive high grade gliomas

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Abstract

Purpose

An increased incidence in hematologic toxicity has been reported with the addition of bevacizumab to lomustine for patients with recurrent or progressive high grade gliomas (HGG). Data regarding incidence of toxicity with combination bevacizumab and carmustine is limited. The purpose of this study is to compare toxicity of single agent carmustine and carmustine plus bevacizumab for patients with HGGs.

Methods

This single center retrospective study at Memorial Sloan Kettering Cancer Center included pathologically confirmed HGG with age ≥ 18 years who received carmustine between January 2003 and May 2017.

Results

Sixty-five patients with HGGs collectively received 110 doses of BCNU during the specified time period. Sixteen patients received single agent BCNU (30 doses); 49 patients received combination bevacizumab with BCNU (80 doses). There was no significant difference in incidence or grade of toxicity between single agent and combination therapy with respect to hepatotoxicity, leukopenia, lymphopenia, neutropenia, anemia, and thrombocytopenia. Rates of grade 3 and 4 neutropenia (20% vs 13.8%, p = 0.55) and thrombocytopenia (23.3% vs 23.8%, p = 1) did not differ between single agent BCNU versus combination therapy. When stratified based on dose ( < 150 mg/m2, 150 mg/m2, > 150 mg/m2), there was no statistically significant difference between the two groups with respect to grade 3 and 4 neutropenia or thrombocytopenia.

Conclusions

This is the first study to report the toxicity of carmustine with or without bevacizumab for the treatment of recurrent and refractory HGG. The addition of bevacizumab to carmustine did not increase incidence or grade of hematologic toxicity when compared to single agent carmustine.

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Data availability

Data are available on request to the authors.

References

  1. National Comprehensive Cancer Network (2019) Central nervous system cancers (Version 1.2019). https://www.nccn.org/professionals/physician_gls/pdf/cns.pdf. Accessed August 8, 2019

  2. Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJB, Janzer RC, Ludwin SK, Allgeier A, Fisher B, Belanger K, Hau P, Brandes AA, Gijtenbeek J, Marosi C, Vecht CJ, Mokhtari K, Wesseling P, Villa S, Eisenhauer E, Gorlia T, Weller M, Lacombe D, Cairncross JG, Mirimanoff R-O (2009) Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol 10:459–466. https://doi.org/10.1016/S1470-2045(09)70025-7

    Article  CAS  PubMed  Google Scholar 

  3. Gorlia T, Stupp R, Brandes AA, Rampling RR, Fumoleau P, Dittrich C, Campone MM, Twelves CC, Raymond E, Hegi ME, Lacombe D, van den Bent MJ (2012) New prognostic factors and calculators for outcome prediction in patients with recurrent glioblastoma: a pooled analysis of EORTC Brain Tumour Group phase I and II clinical trials. Eur J Cancer 48:1176–1184. https://doi.org/10.1016/j.ejca.2012.02.004

    Article  PubMed  Google Scholar 

  4. Nabors LB, Portnow J, Baehring J, Brem H, Brown P, Butowski N, Chamberlain MC, Fenstermaker RA, Friedman A, Gilbert MR, Hattangadi-Gluth J, Holdhoff M, Junck L, Kaley T, Lawson R, Loeffler JS, Lovely MP, Moots PL, Mrugala MM, Newton HB, Parney I, Raizer JJ, Recht L, Shonka N, Shrieve DC, Sills AK Jr, Swinnen LJ, Tran D, Tran N, Vrionis FD, Weiss S, Wen PY, McMillian N, Engh AM (2015) Central nervous system cancers, version 1.2018. J Natl Compr Cancer Netw 13:1191–1202

    Article  CAS  Google Scholar 

  5. Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996. https://doi.org/10.1056/NEJMoa043330

    Article  CAS  PubMed  Google Scholar 

  6. Avastin (Bevacizumab) (2014) Prescribing information. Genentech Inc, San Francisco, CA

  7. Gliadel (Carmustine Wafers) (2013) Prescribing information. In: Arbor Pharmaceuticals L (ed). Atlanta, GA

  8. Stupp R, Wong ET, Kanner AA, Steinberg D, Engelhard H, Heidecke V, Kirson ED, Taillibert S, Liebermann F, Dbaly V, Ram Z, Villano JL, Rainov N, Weinberg U, Schiff D, Kunschner L, Raizer J, Honnorat J, Sloan A, Malkin M, Landolfi JC, Payer F, Mehdorn M, Weil RJ, Pannullo SC, Westphal M, Smrcka M, Chin L, Kostron H, Hofer S, Bruce J, Cosgrove R, Paleologous N, Palti Y, Gutin PH (2012) NovoTTF-100A versus physician's choice chemotherapy in recurrent glioblastoma: a randomised phase III trial of a novel treatment modality. Eur J Cancer 48:2192–2202. https://doi.org/10.1016/j.ejca.2012.04.011

    Article  PubMed  Google Scholar 

  9. BiCNU (carmustine for injection) (2007) Prescribing information. In: Company B-MS (ed). Princeton, NJ

  10. Taal W, Oosterkamp HM, Walenkamp AM, Dubbink HJ, Beerepoot LV, Hanse MC, Buter J, Honkoop AH, Boerman D, de Vos FY, Dinjens WN, Enting RH, Taphoorn MJ, van den Berkmortel FW, Jansen RL, Brandsma D, Bromberg JE, van Heuvel I, Vernhout RM, van der Holt B, van den Bent MJ (2014) Single-agent bevacizumab or lomustine versus a combination of bevacizumab plus lomustine in patients with recurrent glioblastoma (BELOB trial): a randomised controlled phase 2 trial. Lancet Oncol 15:943–953. https://doi.org/10.1016/s1470-2045(14)70314-6

    Article  CAS  PubMed  Google Scholar 

  11. Wick W, Gorlia T, Bendszus M, Taphoorn M, Sahm F, Harting I, Brandes AA, Taal W, Domont J, Idbaih A, Campone M, Clement PM, Stupp R, Fabbro M, Le Rhun E, Dubois F, Weller M, von Deimling A, Golfinopoulos V, Bromberg JC, Platten M, Klein M, van den Bent MJ (2017) Lomustine and bevacizumab in progressive glioblastoma. N Engl J Med 377:1954–1963. https://doi.org/10.1056/NEJMoa1707358

    Article  CAS  PubMed  Google Scholar 

  12. Wen PY, Macdonald DR, Reardon DA, Cloughesy TF, Sorensen AG, Galanis E, Degroot J, Wick W, Gilbert MR, Lassman AB, Tsien C, Mikkelsen T, Wong ET, Chamberlain MC, Stupp R, Lamborn KR, Vogelbaum MA, van den Bent MJ, Chang SM (2010) Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J Clin Oncol 28:1963–1972. https://doi.org/10.1200/jco.2009.26.3541

    Article  PubMed  Google Scholar 

  13. Rahman R, Hempfling K, Norden AD, Reardon DA, Nayak L, Rinne ML, Beroukhim R, Doherty L, Ruland S, Rai A, Rifenburg J, LaFrankie D, Alexander BM, Huang RY, Wen PY, Lee EQ (2014) Retrospective study of carmustine or lomustine with bevacizumab in recurrent glioblastoma patients who have failed prior bevacizumab. Neuro-oncology 16:1523–1529. https://doi.org/10.1093/neuonc/nou118

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Reithmeier T, Graf E, Piroth T, Trippel M, Pinsker MO, Nikkhah G (2010) BCNU for recurrent glioblastoma multiforme: efficacy, toxicity and prognostic factors. BMC Cancer 10:30. https://doi.org/10.1186/1471-2407-10-30

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Brandes AA, Tosoni A, Amista P, Nicolardi L, Grosso D, Berti F, Ermani M (2004) How effective is BCNU in recurrent glioblastoma in the modern era? A phase II trial. Neurology 63:1281–1284

    Article  CAS  PubMed  Google Scholar 

  16. van den Bent MJ, Brandes AA, Rampling R, Kouwenhoven MC, Kros JM, Carpentier AF, Clement PM, Frenay M, Campone M, Baurain JF, Armand JP, Taphoorn MJ, Tosoni A, Kletzl H, Klughammer B, Lacombe D, Gorlia T (2009) Randomized phase II trial of erlotinib versus temozolomide or carmustine in recurrent glioblastoma: EORTC brain tumor group study 26034. J Clin Oncol 27:1268–1274. https://doi.org/10.1200/jco.2008.17.5984

    Article  PubMed  PubMed Central  Google Scholar 

  17. Brandsma D, van den Bent MJ (2009) Pseudoprogression and pseudoresponse in the treatment of gliomas. Curr Opin Neurol 22:633–638. https://doi.org/10.1097/WCO.0b013e328332363e

    Article  PubMed  Google Scholar 

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Funding

This research was funded in part through the NIH/NCI Cancer Center Support Grant P30 CA008748.

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Authors and Affiliations

  1. Department of Pharmacy, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY, 10065, USA

    Prakirthi Yerram, Samantha N. Reiss & Lisa Modelevsky

  2. Department of Neurology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY, 10065, USA

    Igor T. Gavrilovic & Thomas Kaley

Authors
  1. Prakirthi Yerram
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  2. Samantha N. Reiss
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  3. Lisa Modelevsky
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  4. Igor T. Gavrilovic
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  5. Thomas Kaley
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by PY and SNR. The first draft of the manuscript was written by PY and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Prakirthi Yerram.

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Yerram, P., Reiss, S.N., Modelevsky, L. et al. Evaluation of toxicity of carmustine with or without bevacizumab in patients with recurrent or progressive high grade gliomas. J Neurooncol 145, 57–63 (2019). https://doi.org/10.1007/s11060-019-03266-0

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  • DOI: https://doi.org/10.1007/s11060-019-03266-0

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