Allan Lipton is on the speaker's bureau for Norvartis. He also has served as a consultant for and given testimony on behalf of Novartis. Richard Cook receives honoraria from and has a consultant's agreement with Novartis. Fred Saad has served on advisory boards of and receives honoraria and research funds from Novartis. Pierre Major has no financial interests in Novartis. Patrick Garnero has received consultant fees from Novartis. Evangelos Terpos has received an honorarium for participation in an advisory board from Novartis. Janet Brown has participated in an advisory board for Novartis. Robert Coleman receives honoraria, consultancy payments, and research funds from Novartis. He has also given expert testimony on behalf of Novartis.
Normalization of bone markers is associated with improved survival in patients with bone metastases from solid tumors and elevated bone resorption receiving zoledronic acid
Version of Record online: 5 MAY 2008
Copyright © 2008 American Cancer Society
Volume 113, Issue 1, pages 193–201, 1 July 2008
How to Cite
Lipton, A., Cook, R., Saad, F., Major, P., Garnero, P., Terpos, E., Brown, J. E. and Coleman, R. E. (2008), Normalization of bone markers is associated with improved survival in patients with bone metastases from solid tumors and elevated bone resorption receiving zoledronic acid. Cancer, 113: 193–201. doi: 10.1002/cncr.23529
- Issue online: 20 JUN 2008
- Version of Record online: 5 MAY 2008
- Manuscript Accepted: 15 FEB 2008
- Manuscript Revised: 5 FEB 2008
- Manuscript Received: 29 NOV 2007
- Novartis Pharmaceuticals
- neoplasm metastasis;
- NTX telopeptide;
For patients with bone metastases, high N-telopeptide of type I collagen (NTX) levels correlate with increased risks of skeletal-related events and death. However, the relation between NTX decreases and clinical benefits is unclear.
Correlations between NTX normalization during treatment and clinical outcome were retrospectively analyzed in 3 large, phase 3 trials. Urinary NTX levels were measured at baseline and at Month 3 in patients with bone metastases from breast cancer (BC; n = 578), hormone-refractory prostate cancer (HRPC; n = 472), or nonsmall-cell lung cancer and other solid tumors (NSCLC/OST; n = 291) who received zoledronic acid or control (pamidronate for BC; placebo for HRPC and NSCLC/OST) for up to 24 months. NTX levels were characterized as normal (N; <64 nmol/mmol creatinine) or elevated (E; ≥64 nmol/mmol creatinine).
After 3 months of zoledronic acid, most N-group patients maintained normal levels; however, most E-group patients normalized their NTX levels (BC, 81%; HRPC, 70%; NSCLC/OST, 81%). In contrast, NTX levels normalized with pamidronate in 65% of BC, with placebo in 8% of HRPC, and in 17% of NSCLC/OST E-group patients. Normalized NTX correlated with improved overall survival versus persistently elevated NTX (significant for zoledronic acid-treated patients; trend for placebo-treated patients). Moreover, percentage reductions from baseline NTX levels correlated with benefits regardless of whether patients transitioned from E to N.
Zoledronic acid normalizes or maintains normal NTX levels in most patients with bone metastases. Normalized NTX within 3 months of treatment, versus persistently elevated NTX, was associated with reduced risks of skeletal complications and death. Cancer 2008. © 2008 American Cancer Society.