Zoledronic acid and survival in breast cancer patients with bone metastases and elevated markers of osteoclast activity

Allan Lipton, Richard J. Cook, Pierre Major, Matthew R. Smith, Robert E. Coleman

Research output: Contribution to journalArticle

86 Citations (Scopus)

Abstract

Objective. Most breast cancer patients with bone metastases will receive bisphosphonate treatment. This post hoc analysis investigated whether early normalization of urinary N-telopeptide of type I collagen (NTX) levels during bisphosphonate therapy correlates with a long-term reduction in skeletal-related event (SRE) risk and mortality in patients with breast cancer. Methods. This was a retrospective subset analysis of a phase III randomized trial comparing i.v. zoledronic acid with pamidronate treatment in patients with bone metastases from breast cancer or multiple myeloma. Patients with breast cancer who had NTX assessments at baseline and at months 1 and 3 (n = 342) were classified as normal (NTX <64 nmol/mmol creatinine) or elevated (NTX ≥64 nmol/mmol creatinine). The relative risk for an SRE or death was estimated with Cox regression models. Results. Among the 328 evaluable patients treated with zoledronic acid, 196 patients (59.7%) had elevated baseline NTX, with 149 of those patients (76.0%) having normalized NTX levels and 31 patients (15.8%) having persistently elevated NTX levels at 3 months. The normalized NTX group had significantly lower risks for a first SRE, a first fracture or surgery to bone, or death than the group that had persistently elevated NTX levels. Conclusions. These results suggest that early normalization of elevated baseline NTX while receiving zoledronic acid is associated with longer event-free and overall survival times compared with persistently elevated NTX. Further analyses in cancer patients with elevated marker levels are warranted to confirm the implications of these findings.

Original languageEnglish (US)
Pages (from-to)1035-1043
Number of pages9
JournalOncologist
Volume12
Issue number9
DOIs
StatePublished - Sep 1 2007

Fingerprint

zoledronic acid
Osteoclasts
Breast Neoplasms
Neoplasm Metastasis
Bone and Bones
Survival
pamidronate
Diphosphonates
Creatinine

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Lipton, Allan ; Cook, Richard J. ; Major, Pierre ; Smith, Matthew R. ; Coleman, Robert E. / Zoledronic acid and survival in breast cancer patients with bone metastases and elevated markers of osteoclast activity. In: Oncologist. 2007 ; Vol. 12, No. 9. pp. 1035-1043.
@article{472ab47c9f17496286df5117e79f64ff,
title = "Zoledronic acid and survival in breast cancer patients with bone metastases and elevated markers of osteoclast activity",
abstract = "Objective. Most breast cancer patients with bone metastases will receive bisphosphonate treatment. This post hoc analysis investigated whether early normalization of urinary N-telopeptide of type I collagen (NTX) levels during bisphosphonate therapy correlates with a long-term reduction in skeletal-related event (SRE) risk and mortality in patients with breast cancer. Methods. This was a retrospective subset analysis of a phase III randomized trial comparing i.v. zoledronic acid with pamidronate treatment in patients with bone metastases from breast cancer or multiple myeloma. Patients with breast cancer who had NTX assessments at baseline and at months 1 and 3 (n = 342) were classified as normal (NTX <64 nmol/mmol creatinine) or elevated (NTX ≥64 nmol/mmol creatinine). The relative risk for an SRE or death was estimated with Cox regression models. Results. Among the 328 evaluable patients treated with zoledronic acid, 196 patients (59.7{\%}) had elevated baseline NTX, with 149 of those patients (76.0{\%}) having normalized NTX levels and 31 patients (15.8{\%}) having persistently elevated NTX levels at 3 months. The normalized NTX group had significantly lower risks for a first SRE, a first fracture or surgery to bone, or death than the group that had persistently elevated NTX levels. Conclusions. These results suggest that early normalization of elevated baseline NTX while receiving zoledronic acid is associated with longer event-free and overall survival times compared with persistently elevated NTX. Further analyses in cancer patients with elevated marker levels are warranted to confirm the implications of these findings.",
author = "Allan Lipton and Cook, {Richard J.} and Pierre Major and Smith, {Matthew R.} and Coleman, {Robert E.}",
year = "2007",
month = "9",
day = "1",
doi = "10.1634/theoncologist.12-9-1035",
language = "English (US)",
volume = "12",
pages = "1035--1043",
journal = "Oncologist",
issn = "1083-7159",
publisher = "AlphaMed Press",
number = "9",

}

Zoledronic acid and survival in breast cancer patients with bone metastases and elevated markers of osteoclast activity. / Lipton, Allan; Cook, Richard J.; Major, Pierre; Smith, Matthew R.; Coleman, Robert E.

In: Oncologist, Vol. 12, No. 9, 01.09.2007, p. 1035-1043.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Zoledronic acid and survival in breast cancer patients with bone metastases and elevated markers of osteoclast activity

AU - Lipton, Allan

AU - Cook, Richard J.

AU - Major, Pierre

AU - Smith, Matthew R.

AU - Coleman, Robert E.

PY - 2007/9/1

Y1 - 2007/9/1

N2 - Objective. Most breast cancer patients with bone metastases will receive bisphosphonate treatment. This post hoc analysis investigated whether early normalization of urinary N-telopeptide of type I collagen (NTX) levels during bisphosphonate therapy correlates with a long-term reduction in skeletal-related event (SRE) risk and mortality in patients with breast cancer. Methods. This was a retrospective subset analysis of a phase III randomized trial comparing i.v. zoledronic acid with pamidronate treatment in patients with bone metastases from breast cancer or multiple myeloma. Patients with breast cancer who had NTX assessments at baseline and at months 1 and 3 (n = 342) were classified as normal (NTX <64 nmol/mmol creatinine) or elevated (NTX ≥64 nmol/mmol creatinine). The relative risk for an SRE or death was estimated with Cox regression models. Results. Among the 328 evaluable patients treated with zoledronic acid, 196 patients (59.7%) had elevated baseline NTX, with 149 of those patients (76.0%) having normalized NTX levels and 31 patients (15.8%) having persistently elevated NTX levels at 3 months. The normalized NTX group had significantly lower risks for a first SRE, a first fracture or surgery to bone, or death than the group that had persistently elevated NTX levels. Conclusions. These results suggest that early normalization of elevated baseline NTX while receiving zoledronic acid is associated with longer event-free and overall survival times compared with persistently elevated NTX. Further analyses in cancer patients with elevated marker levels are warranted to confirm the implications of these findings.

AB - Objective. Most breast cancer patients with bone metastases will receive bisphosphonate treatment. This post hoc analysis investigated whether early normalization of urinary N-telopeptide of type I collagen (NTX) levels during bisphosphonate therapy correlates with a long-term reduction in skeletal-related event (SRE) risk and mortality in patients with breast cancer. Methods. This was a retrospective subset analysis of a phase III randomized trial comparing i.v. zoledronic acid with pamidronate treatment in patients with bone metastases from breast cancer or multiple myeloma. Patients with breast cancer who had NTX assessments at baseline and at months 1 and 3 (n = 342) were classified as normal (NTX <64 nmol/mmol creatinine) or elevated (NTX ≥64 nmol/mmol creatinine). The relative risk for an SRE or death was estimated with Cox regression models. Results. Among the 328 evaluable patients treated with zoledronic acid, 196 patients (59.7%) had elevated baseline NTX, with 149 of those patients (76.0%) having normalized NTX levels and 31 patients (15.8%) having persistently elevated NTX levels at 3 months. The normalized NTX group had significantly lower risks for a first SRE, a first fracture or surgery to bone, or death than the group that had persistently elevated NTX levels. Conclusions. These results suggest that early normalization of elevated baseline NTX while receiving zoledronic acid is associated with longer event-free and overall survival times compared with persistently elevated NTX. Further analyses in cancer patients with elevated marker levels are warranted to confirm the implications of these findings.

UR - http://www.scopus.com/inward/record.url?scp=35548960086&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=35548960086&partnerID=8YFLogxK

U2 - 10.1634/theoncologist.12-9-1035

DO - 10.1634/theoncologist.12-9-1035

M3 - Article

VL - 12

SP - 1035

EP - 1043

JO - Oncologist

JF - Oncologist

SN - 1083-7159

IS - 9

ER -