Ixabepilone-associated peripheral neuropathy

Data from across the phase II and III clinical trials

Linda T. Vahdat, Eva S. Thomas, Henri H. Roché, Gabriel N. Hortobagyi, Joseph A. Sparano, Louise Yelle, Monica N. Fornier, Miguel Martín, Craig A. Bunnell, Pralay Mukhopadhyay, Ronald A. Peck, Edith A. Perez

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Purpose Dose-limiting neuropathy is a major adverse event associated with most of the microtubule-stabilizing agentbased chemotherapy regimens. Ixabepilone, a semisynthetic analogue of the natural epothilone B, has activity against a wide range of tumor types. Peripheral neuropathy (PN), associated with ixabepilone treatment, is usually mild to moderate, predominantly sensory and cumulative. Preclinical studies demonstrate that ixabepilone and taxanes produce a similar neurotoxicity profile. Methods We searched databases of phase II/III clinical trials involving patients receiving ixabepilone as a monotherapy or in combination with capecitabine for incidences of neuropathy. Potential risk factors for grade 3/4 PN were identified by a Cox regression analysis on a dataset of 1,540 patients with different tumor types across multiple studies. Results Rates for incidence of ixabepilone-induced severe PN (Common Terminology Criteria for Adverse Events grade 3/4) ranged from 1% in early untreated breast cancer up to 24% in heavily pretreated metastatic breast cancer; grade 4 PN was rare (≤1%). Common symptoms included numbness, paresthesias, and sometimes dysesthesias. Cox regression analysis identified only preexisting neuropathy as a risk factor for increased ixabepilone-associated PN. The management of PN has been primarily through dose adjustments (dose delays and/or dose reduction). Patients had resolution of their neuropathy within a median time of 5 to 6 weeks. Conclusions PN is a dose-limiting toxicity associated with ixabepilone treatment, is reversible in most patients, and can be managed with dose reduction and delays.

Original languageEnglish (US)
Pages (from-to)2661-2668
Number of pages8
JournalSupportive Care in Cancer
Volume20
Issue number11
DOIs
StatePublished - Nov 2012

Fingerprint

Phase III Clinical Trials
Phase II Clinical Trials
Peripheral Nervous System Diseases
Paresthesia
Regression Analysis
Breast Neoplasms
Taxoids
Hypesthesia
Incidence
ixabepilone
Terminology
Microtubules
Neoplasms
Databases
Drug Therapy
Therapeutics

Keywords

  • Breast cancer
  • Epothilone
  • Ixabepilone
  • Microtubules
  • Neuropathy

ASJC Scopus subject areas

  • Oncology

Cite this

Vahdat, L. T., Thomas, E. S., Roché, H. H., Hortobagyi, G. N., Sparano, J. A., Yelle, L., ... Perez, E. A. (2012). Ixabepilone-associated peripheral neuropathy: Data from across the phase II and III clinical trials. Supportive Care in Cancer, 20(11), 2661-2668. https://doi.org/10.1007/s00520-012-1384-0

Ixabepilone-associated peripheral neuropathy : Data from across the phase II and III clinical trials. / Vahdat, Linda T.; Thomas, Eva S.; Roché, Henri H.; Hortobagyi, Gabriel N.; Sparano, Joseph A.; Yelle, Louise; Fornier, Monica N.; Martín, Miguel; Bunnell, Craig A.; Mukhopadhyay, Pralay; Peck, Ronald A.; Perez, Edith A.

In: Supportive Care in Cancer, Vol. 20, No. 11, 11.2012, p. 2661-2668.

Research output: Contribution to journalArticle

Vahdat, LT, Thomas, ES, Roché, HH, Hortobagyi, GN, Sparano, JA, Yelle, L, Fornier, MN, Martín, M, Bunnell, CA, Mukhopadhyay, P, Peck, RA & Perez, EA 2012, 'Ixabepilone-associated peripheral neuropathy: Data from across the phase II and III clinical trials', Supportive Care in Cancer, vol. 20, no. 11, pp. 2661-2668. https://doi.org/10.1007/s00520-012-1384-0
Vahdat, Linda T. ; Thomas, Eva S. ; Roché, Henri H. ; Hortobagyi, Gabriel N. ; Sparano, Joseph A. ; Yelle, Louise ; Fornier, Monica N. ; Martín, Miguel ; Bunnell, Craig A. ; Mukhopadhyay, Pralay ; Peck, Ronald A. ; Perez, Edith A. / Ixabepilone-associated peripheral neuropathy : Data from across the phase II and III clinical trials. In: Supportive Care in Cancer. 2012 ; Vol. 20, No. 11. pp. 2661-2668.
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abstract = "Purpose Dose-limiting neuropathy is a major adverse event associated with most of the microtubule-stabilizing agentbased chemotherapy regimens. Ixabepilone, a semisynthetic analogue of the natural epothilone B, has activity against a wide range of tumor types. Peripheral neuropathy (PN), associated with ixabepilone treatment, is usually mild to moderate, predominantly sensory and cumulative. Preclinical studies demonstrate that ixabepilone and taxanes produce a similar neurotoxicity profile. Methods We searched databases of phase II/III clinical trials involving patients receiving ixabepilone as a monotherapy or in combination with capecitabine for incidences of neuropathy. Potential risk factors for grade 3/4 PN were identified by a Cox regression analysis on a dataset of 1,540 patients with different tumor types across multiple studies. Results Rates for incidence of ixabepilone-induced severe PN (Common Terminology Criteria for Adverse Events grade 3/4) ranged from 1{\%} in early untreated breast cancer up to 24{\%} in heavily pretreated metastatic breast cancer; grade 4 PN was rare (≤1{\%}). Common symptoms included numbness, paresthesias, and sometimes dysesthesias. Cox regression analysis identified only preexisting neuropathy as a risk factor for increased ixabepilone-associated PN. The management of PN has been primarily through dose adjustments (dose delays and/or dose reduction). Patients had resolution of their neuropathy within a median time of 5 to 6 weeks. Conclusions PN is a dose-limiting toxicity associated with ixabepilone treatment, is reversible in most patients, and can be managed with dose reduction and delays.",
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T1 - Ixabepilone-associated peripheral neuropathy

T2 - Data from across the phase II and III clinical trials

AU - Vahdat, Linda T.

AU - Thomas, Eva S.

AU - Roché, Henri H.

AU - Hortobagyi, Gabriel N.

AU - Sparano, Joseph A.

AU - Yelle, Louise

AU - Fornier, Monica N.

AU - Martín, Miguel

AU - Bunnell, Craig A.

AU - Mukhopadhyay, Pralay

AU - Peck, Ronald A.

AU - Perez, Edith A.

PY - 2012/11

Y1 - 2012/11

N2 - Purpose Dose-limiting neuropathy is a major adverse event associated with most of the microtubule-stabilizing agentbased chemotherapy regimens. Ixabepilone, a semisynthetic analogue of the natural epothilone B, has activity against a wide range of tumor types. Peripheral neuropathy (PN), associated with ixabepilone treatment, is usually mild to moderate, predominantly sensory and cumulative. Preclinical studies demonstrate that ixabepilone and taxanes produce a similar neurotoxicity profile. Methods We searched databases of phase II/III clinical trials involving patients receiving ixabepilone as a monotherapy or in combination with capecitabine for incidences of neuropathy. Potential risk factors for grade 3/4 PN were identified by a Cox regression analysis on a dataset of 1,540 patients with different tumor types across multiple studies. Results Rates for incidence of ixabepilone-induced severe PN (Common Terminology Criteria for Adverse Events grade 3/4) ranged from 1% in early untreated breast cancer up to 24% in heavily pretreated metastatic breast cancer; grade 4 PN was rare (≤1%). Common symptoms included numbness, paresthesias, and sometimes dysesthesias. Cox regression analysis identified only preexisting neuropathy as a risk factor for increased ixabepilone-associated PN. The management of PN has been primarily through dose adjustments (dose delays and/or dose reduction). Patients had resolution of their neuropathy within a median time of 5 to 6 weeks. Conclusions PN is a dose-limiting toxicity associated with ixabepilone treatment, is reversible in most patients, and can be managed with dose reduction and delays.

AB - Purpose Dose-limiting neuropathy is a major adverse event associated with most of the microtubule-stabilizing agentbased chemotherapy regimens. Ixabepilone, a semisynthetic analogue of the natural epothilone B, has activity against a wide range of tumor types. Peripheral neuropathy (PN), associated with ixabepilone treatment, is usually mild to moderate, predominantly sensory and cumulative. Preclinical studies demonstrate that ixabepilone and taxanes produce a similar neurotoxicity profile. Methods We searched databases of phase II/III clinical trials involving patients receiving ixabepilone as a monotherapy or in combination with capecitabine for incidences of neuropathy. Potential risk factors for grade 3/4 PN were identified by a Cox regression analysis on a dataset of 1,540 patients with different tumor types across multiple studies. Results Rates for incidence of ixabepilone-induced severe PN (Common Terminology Criteria for Adverse Events grade 3/4) ranged from 1% in early untreated breast cancer up to 24% in heavily pretreated metastatic breast cancer; grade 4 PN was rare (≤1%). Common symptoms included numbness, paresthesias, and sometimes dysesthesias. Cox regression analysis identified only preexisting neuropathy as a risk factor for increased ixabepilone-associated PN. The management of PN has been primarily through dose adjustments (dose delays and/or dose reduction). Patients had resolution of their neuropathy within a median time of 5 to 6 weeks. Conclusions PN is a dose-limiting toxicity associated with ixabepilone treatment, is reversible in most patients, and can be managed with dose reduction and delays.

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KW - Ixabepilone

KW - Microtubules

KW - Neuropathy

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