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

Aixa Elena Soyano; Michael Shafique; Roohi Ismail-Khan; Dawn Goodridge; David Boulware; Hatem Soliman; Hyo Sook Han

doi:doi:10.11648/j.crj.20210903.17

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

Aixa Elena Soyano, Michael Shafique, Roohi Ismail-Khan, Dawn Goodridge, David Boulware, Hatem Soliman, Hyo Sook Han

Published in Cancer Research Journal (Volume 9, Issue 3)

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), 2024. Published by Science Publishing Group

Keywords

Eribulin, Breast Neoplasms, Drug Therapy, Breast Cancer

References

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[14]	Swami U, Petrylak DP, Raftopoulos H, Shuster DE, Wang G, Kumar V, Martinez G, Goel S, Aisner J: Phase IB study of eribulin mesylate in combination with carboplatin in patients with advanced solid tumors. J Clin Oncol 2010, 28 (15): 2589.
[15]	Romano PM, Baraibar I, Fernandez-Hidalgo O, Santisteban M, Espinos J, Salas D, Sala P, Gardeazabal I, Oteiza LZ, Aramendia JM: Eribulin and carboplatin in heavily pretreated patients with metastatic breast cancer: A single institution experience. J Clin Oncol 2015, 33 (28): 122.
[16]	Kaklamani VG, Jeruss JS, Hughes E, Siziopikou K, Timms KM, Gutin A, Abkevich V, Sangale Z, Solimeno C, Brown KL et al: Phase II neoadjuvant clinical trial of carboplatin and eribulin in women with triple negative early-stage breast cancer (NCT01372579). Breast Cancer Res Treat 2015, 151 (3): 629-638.
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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

Aixa Elena Soyano

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

Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, USA
Roohi Ismail-Khan

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

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

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

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

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

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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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