Phase I/II study of sorafenib with anastrozole in patients with hormone receptor positive aromatase inhibitor resistant metastatic breast cancer

Claudine Isaacs, Pia Herbolsheimer, Minetta C Liu, Mary Wilkinson, Yvonne Ottaviano, Gina G. Chung, Robert Warren, Jennifer Eng-Wong, Philip Cohen, Karen L. Smith, Karen Creswell, Antonella Novielli, Rebecca Slack

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

We evaluated the use of sorafenib to overcome resistance to aromatase inhibitors (AIs) in patients with metastatic breast cancer who had disease recurrence or progression while on AIs. We performed a multi-institution phase I/II study of sorafenib and anastrozole 1 mg daily in 35 postmenopausal females with hormone receptor positive metastatic breast cancer resistant to AIs. Primary objectives were to determine the dose of sorafenib in conjunction with anastrozole and the clinical benefit rate (CBR) (complete response [CR], partial response [PR], or stable disease [SD] ≥ 24 weeks). Secondary objectives were to determine toxicity and to evaluate if response was associated with change in number of circulating endothelial cells or circulating endothelial progenitor cells. Based on the phase I portion, sorafenib 400 mg twice daily was selected as the phase II dose. Among 35 patients, 7 had SD ≥ 24 weeks, 1 had PR ≥ 24 weeks, and 14 had progressive disease (PD) ≤ 24 weeks, corresponding to a CBR of 23%. The most common adverse events (all; Grade 3/4) were fatigue (66%; 17%), diarrhea (63%; 6%), nausea (60%; 9%), and hand-foot syndrome (57%; 34%). Dose reduction occurred in 77% of the patients and 31% came off study due to toxicity. The combination of sorafenib and anastrozole demonstrated a 23% CBR in patients with hormone receptor positive, AI-resistant metastatic breast cancer, which may be attributable to the restoration of sensitivity to AIs. Toxicities occurred frequently resulting in a high rate of discontinuation.

Original languageEnglish (US)
Pages (from-to)137-143
Number of pages7
JournalBreast Cancer Research and Treatment
Volume125
Issue number1
DOIs
StatePublished - Jan 2011
Externally publishedYes

Fingerprint

Aromatase Inhibitors
Hormones
Breast Neoplasms
Hand-Foot Syndrome
Nausea
Fatigue
Diarrhea
Endothelial Cells
sorafenib
anastrozole
Recurrence

Keywords

  • Anastrozole
  • Aromatase inhibitor
  • Breast cancer
  • Endocrine resistance
  • Sorafenib

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Phase I/II study of sorafenib with anastrozole in patients with hormone receptor positive aromatase inhibitor resistant metastatic breast cancer. / Isaacs, Claudine; Herbolsheimer, Pia; Liu, Minetta C; Wilkinson, Mary; Ottaviano, Yvonne; Chung, Gina G.; Warren, Robert; Eng-Wong, Jennifer; Cohen, Philip; Smith, Karen L.; Creswell, Karen; Novielli, Antonella; Slack, Rebecca.

In: Breast Cancer Research and Treatment, Vol. 125, No. 1, 01.2011, p. 137-143.

Research output: Contribution to journalArticle

Isaacs, C, Herbolsheimer, P, Liu, MC, Wilkinson, M, Ottaviano, Y, Chung, GG, Warren, R, Eng-Wong, J, Cohen, P, Smith, KL, Creswell, K, Novielli, A & Slack, R 2011, 'Phase I/II study of sorafenib with anastrozole in patients with hormone receptor positive aromatase inhibitor resistant metastatic breast cancer', Breast Cancer Research and Treatment, vol. 125, no. 1, pp. 137-143. https://doi.org/10.1007/s10549-010-1226-z
Isaacs, Claudine ; Herbolsheimer, Pia ; Liu, Minetta C ; Wilkinson, Mary ; Ottaviano, Yvonne ; Chung, Gina G. ; Warren, Robert ; Eng-Wong, Jennifer ; Cohen, Philip ; Smith, Karen L. ; Creswell, Karen ; Novielli, Antonella ; Slack, Rebecca. / Phase I/II study of sorafenib with anastrozole in patients with hormone receptor positive aromatase inhibitor resistant metastatic breast cancer. In: Breast Cancer Research and Treatment. 2011 ; Vol. 125, No. 1. pp. 137-143.
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