Osteonecrosis of the jaw and oral health-related quality of life after adjuvant zoledronic acid: an adjuvant zoledronic acid to reduce recurrence trial subprotocol (BIG01/04).

Abstract

PURPOSE:

In patients with early breast cancer, adjuvant zoledronic acid (zoledronate) may reduce recurrence and improve survival. However, zoledronate is associated with the occasional development of osteonecrosis of the jaw (ONJ). We report on the frequency of ONJ and investigate oral health-related quality of life (Oral-QoL) in a large randomized trial (Adjuvant Zoledronic Acid to Reduce Recurrence [AZURE]).

PATIENTS AND METHODS:

Three thousand three hundred sixty women with stage II or III breast cancer were randomly assigned to receive standard adjuvant systemic therapy alone or with zoledronate administered at a dose of 4 mg for 19 doses over 5 years. All potential occurrences of ONJ were reported as serious adverse events and centrally reviewed. Additionally, we invited 486 study participants to complete the Oral Health Impact Profile-14 (OHIP-14) to assess Oral-QoL around the time the patients completed 5 years on study. Multivariable linear regression was used to calculate mean scores and 95% CIs in addition to identifying independent prognostic factors.

RESULTS:

With a median follow-up time of 73.9 months (interquartile range, 60.7 to 84.2 months), 33 possible cases of ONJ were reported, all in the zoledronate-treated patients. Twenty-six cases were confirmed as being consistent with a diagnosis of ONJ, representing a cumulative incidence of 2.1% (95% CI, 0.9% to 3.3%) in the zoledronate arm. Three hundred sixty-two patients (74%) returned the OHIP-14 questionnaire. Neither the prevalence nor severity of impacts on Oral-QoL differed significantly between zoledronate patients and control patients.

CONCLUSION:

Adjuvant zoledronate used in the intensive schedule studied in the AZURE trial is associated with a low incidence of ONJ but does not seem to adversely affect Oral-QoL.

• Authors: Emma J Rathbone, Janet E Brown, Helen C Marshall, Michelle Collinson, Victoria Liversedge, Geraldine A Murden, David Cameron, Richard Bell, Saiqa Spensley, Rajiv Agrawal, Rema Jyothirmayi, Prabir Chakraborti, Frances Yuille, Robert E Coleman
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 31 Issue 21 Pg. 2685-91 (Jul 20 2013) ISSN: 1527-7755 [Electronic] United States
• PMID: 23796998 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Bone Density Conservation Agents
• Diphosphonates
• Imidazoles
• Zoledronic Acid

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Bone Density Conservation Agents (administration & dosage, adverse effects)
• Breast Neoplasms (drug therapy, pathology)
• Chemotherapy, Adjuvant
• Diphosphonates (administration & dosage, adverse effects)
• Female
• Humans
• Imidazoles (administration & dosage, adverse effects)
• Jaw Diseases (chemically induced, drug therapy)
• Middle Aged
• Oral Health
• Osteonecrosis (chemically induced, drug therapy)
• Quality of Life
• Zoledronic Acid