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A Phase 1 Dose Escalation Study of Eribulin in Combination with Weekly Carboplatin for the Treatment of Metastatic Breast Cancer

Received: 2 August 2021     Accepted: 24 August 2021     Published: 31 August 2021
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Abstract

Background: Metastatic breast cancer is a common and devastating diagnosis. New strategies for treatment are needed to help improve outcomes. Eribulin is an anti-microtubule agent approved in 2010 for advanced breast cancer. Combination with other chemotherapeutic agents provides an alternative treatment option for these patients. Purpose: This study evaluates the safety, tolerability and activity of eribulin and weekly carboplatin in a dose-escalation schema in patients with metastatic breast cancer. Methods: Patients were treated with eribulin and carboplatin AUC 2 administered on the first and eighth days of a 21-day cycle. Three doses of eribulin (0.9, 1.1 and 1.4 mg/m2) were examined. An additional 10 patients were enrolled into an expansion cohort at the recommended Phase 2 dose. Results: A total of 19 patients were treated, including 10 patients in the dose expansion cohort. There was no dose limiting toxicity related to the study therapy in the dose escalation cohorts. Grade 3 toxicities included neutropenia (21%), anemia (10%), fatigue (10%), peripheral sensory neuropathy (10%), infusion related reactions (5%), pericardial effusion (5%), diarrhea (5%) and pleural effusion (5%). Twenty-six percent of patients had grade 4 neutropenia, but there were no events of sepsis or febrile neutropenia. The maximum tolerated dose (MTD) of eribulin in combination with carboplatin AUC 2 was determined to be 1.4 mg/m2. Four patients experienced clinical benefit, 2 patients with stable disease greater than 6 months and 2 patients with partial response, demonstrating a clinical benefit rate of 21%. Conclusion: Eribulin and weekly carboplatin appeared to be safe and well tolerated with demonstrated clinical benefit. The recommended Phase 2 dose level was 1.4 mg/m2 of eribulin. Further studies can be pursued for this combination regimen to establish its efficacy.

Published in Cancer Research Journal (Volume 9, Issue 3)
DOI 10.11648/j.crj.20210903.17
Page(s) 171-175
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2021. Published by Science Publishing Group

Keywords

Eribulin, Breast Neoplasms, Drug Therapy, Breast Cancer

References
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Cite This Article
  • APA Style

    Aixa Elena Soyano, Michael Shafique, Roohi Ismail-Khan, Dawn Goodridge, David Boulware, et al. (2021). A Phase 1 Dose Escalation Study of Eribulin in Combination with Weekly Carboplatin for the Treatment of Metastatic Breast Cancer. Cancer Research Journal, 9(3), 171-175. https://doi.org/10.11648/j.crj.20210903.17

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    ACS Style

    Aixa Elena Soyano; Michael Shafique; Roohi Ismail-Khan; Dawn Goodridge; David Boulware, et al. A Phase 1 Dose Escalation Study of Eribulin in Combination with Weekly Carboplatin for the Treatment of Metastatic Breast Cancer. Cancer Res. J. 2021, 9(3), 171-175. doi: 10.11648/j.crj.20210903.17

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    AMA Style

    Aixa Elena Soyano, Michael Shafique, Roohi Ismail-Khan, Dawn Goodridge, David Boulware, et al. A Phase 1 Dose Escalation Study of Eribulin in Combination with Weekly Carboplatin for the Treatment of Metastatic Breast Cancer. Cancer Res J. 2021;9(3):171-175. doi: 10.11648/j.crj.20210903.17

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  • @article{10.11648/j.crj.20210903.17,
      author = {Aixa Elena Soyano and Michael Shafique and Roohi Ismail-Khan and Dawn Goodridge and David Boulware and Hatem Soliman and Hyo Sook Han},
      title = {A Phase 1 Dose Escalation Study of Eribulin in Combination with Weekly Carboplatin for the Treatment of Metastatic Breast Cancer},
      journal = {Cancer Research Journal},
      volume = {9},
      number = {3},
      pages = {171-175},
      doi = {10.11648/j.crj.20210903.17},
      url = {https://doi.org/10.11648/j.crj.20210903.17},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.crj.20210903.17},
      abstract = {Background: Metastatic breast cancer is a common and devastating diagnosis. New strategies for treatment are needed to help improve outcomes. Eribulin is an anti-microtubule agent approved in 2010 for advanced breast cancer. Combination with other chemotherapeutic agents provides an alternative treatment option for these patients. Purpose: This study evaluates the safety, tolerability and activity of eribulin and weekly carboplatin in a dose-escalation schema in patients with metastatic breast cancer. Methods: Patients were treated with eribulin and carboplatin AUC 2 administered on the first and eighth days of a 21-day cycle. Three doses of eribulin (0.9, 1.1 and 1.4 mg/m2) were examined. An additional 10 patients were enrolled into an expansion cohort at the recommended Phase 2 dose. Results: A total of 19 patients were treated, including 10 patients in the dose expansion cohort. There was no dose limiting toxicity related to the study therapy in the dose escalation cohorts. Grade 3 toxicities included neutropenia (21%), anemia (10%), fatigue (10%), peripheral sensory neuropathy (10%), infusion related reactions (5%), pericardial effusion (5%), diarrhea (5%) and pleural effusion (5%). Twenty-six percent of patients had grade 4 neutropenia, but there were no events of sepsis or febrile neutropenia. The maximum tolerated dose (MTD) of eribulin in combination with carboplatin AUC 2 was determined to be 1.4 mg/m2. Four patients experienced clinical benefit, 2 patients with stable disease greater than 6 months and 2 patients with partial response, demonstrating a clinical benefit rate of 21%. Conclusion: Eribulin and weekly carboplatin appeared to be safe and well tolerated with demonstrated clinical benefit. The recommended Phase 2 dose level was 1.4 mg/m2 of eribulin. Further studies can be pursued for this combination regimen to establish its efficacy.},
     year = {2021}
    }
    

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  • TY  - JOUR
    T1  - A Phase 1 Dose Escalation Study of Eribulin in Combination with Weekly Carboplatin for the Treatment of Metastatic Breast Cancer
    AU  - Aixa Elena Soyano
    AU  - Michael Shafique
    AU  - Roohi Ismail-Khan
    AU  - Dawn Goodridge
    AU  - David Boulware
    AU  - Hatem Soliman
    AU  - Hyo Sook Han
    Y1  - 2021/08/31
    PY  - 2021
    N1  - https://doi.org/10.11648/j.crj.20210903.17
    DO  - 10.11648/j.crj.20210903.17
    T2  - Cancer Research Journal
    JF  - Cancer Research Journal
    JO  - Cancer Research Journal
    SP  - 171
    EP  - 175
    PB  - Science Publishing Group
    SN  - 2330-8214
    UR  - https://doi.org/10.11648/j.crj.20210903.17
    AB  - Background: Metastatic breast cancer is a common and devastating diagnosis. New strategies for treatment are needed to help improve outcomes. Eribulin is an anti-microtubule agent approved in 2010 for advanced breast cancer. Combination with other chemotherapeutic agents provides an alternative treatment option for these patients. Purpose: This study evaluates the safety, tolerability and activity of eribulin and weekly carboplatin in a dose-escalation schema in patients with metastatic breast cancer. Methods: Patients were treated with eribulin and carboplatin AUC 2 administered on the first and eighth days of a 21-day cycle. Three doses of eribulin (0.9, 1.1 and 1.4 mg/m2) were examined. An additional 10 patients were enrolled into an expansion cohort at the recommended Phase 2 dose. Results: A total of 19 patients were treated, including 10 patients in the dose expansion cohort. There was no dose limiting toxicity related to the study therapy in the dose escalation cohorts. Grade 3 toxicities included neutropenia (21%), anemia (10%), fatigue (10%), peripheral sensory neuropathy (10%), infusion related reactions (5%), pericardial effusion (5%), diarrhea (5%) and pleural effusion (5%). Twenty-six percent of patients had grade 4 neutropenia, but there were no events of sepsis or febrile neutropenia. The maximum tolerated dose (MTD) of eribulin in combination with carboplatin AUC 2 was determined to be 1.4 mg/m2. Four patients experienced clinical benefit, 2 patients with stable disease greater than 6 months and 2 patients with partial response, demonstrating a clinical benefit rate of 21%. Conclusion: Eribulin and weekly carboplatin appeared to be safe and well tolerated with demonstrated clinical benefit. The recommended Phase 2 dose level was 1.4 mg/m2 of eribulin. Further studies can be pursued for this combination regimen to establish its efficacy.
    VL  - 9
    IS  - 3
    ER  - 

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Author Information
  • Department of Breast Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, USA

  • Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, USA

  • Satellite and Community Oncology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, USA

  • Department of Late Phase Research, Florida Cancer Specialists & Research Institute, Tampa, USA

  • Department of Biostatistics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, USA

  • Department of Breast Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, USA

  • Department of Breast Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, USA

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