Cancer Treatment Today

Until very recently. zoledronic acid in the adjuvant setting was only thought to be med. appropiate biannually in women on aromatase inhibitors. Recent data is beginning to change this standard.

Zoledronic Acid (Zometa) study presented at the ASCO 2008 Annual Meeting, demonstrated improved outcomes for pre-menopausal breast cancer patients receiving adjuvant endocrine therapy (some on tamoxifen), increasing disease-free survival by 36% and relapse-free survival by 35% for premenopausal patients who received adjuvant endocrine therapy for early breast cancer (Abstract LBA4). These researchers stated: “There is in fact an indication that zoledronic acid exerts its benefit through a variety of mechanisms, altogether obviously creating a tumor-hostile environment that helps kill micrometastases.”

However, the issue is not fully setted. A recent Cochrane guidelien disagrees. It underlines the fact that overall survival was not increased and that only 3 years followup was provided. It concludes:

• The routine use of either a GnRH analogue with tamoxifen or a GnRH analogue with anastrozole would not be considered standard of care in this setting ….
• The total duration of systemic therapy in this study was only three years, which would be considered suboptimal in most global settings.
• In this special advice report, we specifically define adjuvant endocrine therapy as the systemic therapy given after local therapy (i.e., surgery/radiotherapy) to help decrease the risk of the cancer recurring. This risk of recurrence is reflected through overall survival (OS), disease-free survival (time from randomization to local recurrence, contralateral carcinoma, distant metastasis, secondary carcinoma, and/or death), and or recurrence-free survival (time from randomization to local relapse, contralateral carcinoma, distant metastasis, and/or secondary carcinoma).

It also says the following. Care has been taken in the preparation of the information contained in this report. Nonetheless, any person seeking to apply or consult the report is expected to use independent medical judgment in the context of individual clinical circumstances or seek out the supervision of a qualified clinician. Cancer Care Ontario makes no representation or guarantees of any kind whatsoever regarding the report content or use or application and disclaims any responsibility for its application or use in any way.

A 2012 review(Huang et al) concluded: “Treatment with zoledronic acid had a clear effect on fracture events, and it might contribute an important role for overall survival.

Huang W-W, Huang C, Liu J, Zheng H-Y, Lin L (2012) Zoledronic Acid as an Adjuvant Therapy in Patients with Breast Cancer: A Systematic Review and Meta-Analysis. PLoS ONE 7(7): e40783. doi:10.1371/journal.pone.0040783

Clemons M, Amir E, Haynes AE, Eisen A, Trudeau M. Zoledronic acid as adjuvant therapy in combination with adjuvant endocrine therapy for premenopausal women with early-stage hormone receptor positive breast cancer. Toronto (ON): Cancer Care Ontario (CCO); 2010 Jan 25. 18 p. (CED-CCO special advice report; no. 16).  [8 references]

Gnant, M. et al. Efficacy of Zoledronic acid in premenopausal women with breast cancer receiving adjuvant endocrine therapy – the ABCSG-12 trial. Presented at: the 44th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago, Ill., 31 May – 2 June, 2008; Abstract LBA4.
subsequently published in hte NEJM Volume 360:679-691 February 12, 2009 Number 7

Beat Thuerlimann et al, Guidelines for the adjuvant treatment of postmenopausal women with endocrine-responsive breast cancer: Past, present and future recommendations European Journal of Cancer Volume 43, Issue 1, January 2007, Pages 46-52

Christian Seitz, Advances in the Medical Treatment of Prostate Cancer, Bladder Cancer, Renal Cell Cancer, and Benign Prostatic HyperplasiaRev Urol. 2003 Spring; 5(2): 90–110.
Highlights from the XVIIth Congress of the European Association of Urology, Birmingham, UK, February 23–26, 2002

Presribing information 2012