Zoledronic acid (Zometa)

==General information==
Class/mechanism: Bisphosphonate, inhibits osteoclast activity and bone resorption/turnover, induces osteoclast apoptosis, and inhibits skeletal calcium release by tumor stimulatory factors.Zoledronic acid (Zometa) package insert Zoledronic acid (Zometa) package insert (locally hosted backup)Zometa manufacturer's site
Route: IV
Extravasation: no information
For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as Micromedex, Lexicomp, or the prescribing information. 
==Disease-specific information==
For now this will be a gathering point for RCTs examining the use of this agent, which does not have clear antineoplastic properties; in the future this information may be moved to separate page(s).
*Amgen 20050244: Henry DH, Costa L, Goldwasser F, Hirsh V, Hungria V, Prausova J, Scagliotti GV, Sleeboom H, Spencer A, Vadhan-Raj S, von Moos R, Willenbacher W, Woll PJ, Wang J, Jiang Q, Jun S, Dansey R, Yeh H. Randomized, double-blind study of denosumab versus zoledronic acid in the treatment of bone metastases in patients with advanced cancer (excluding breast and prostate cancer) or multiple myeloma. J Clin Oncol. 2011 Mar 20;29(9):1125-32. Epub 2011 Feb 22. link to original article EuroPMC NCT00330759
*RTOG 0517: Seider MJ, Pugh SL, Langer C, Wyatt G, Demas W, Rashtian A, Clausen CL, Derdel JD, Cleary SF, Peters CA, Ramalingam A, Clarkson JE, Tomblyn M, Rabinovitch RA, Kachnic LA, Berk LB; NRG Oncology. Randomized phase III trial to evaluate radiopharmaceuticals and zoledronic acid in the palliation of osteoblastic metastases from lung, breast, and prostate cancer: report of the NRG Oncology RTOG 0517 trial. Ann Nucl Med. 2018 Oct;32(8):553-560. Epub 2018 Aug 9. link to original article link to PMC article EuroPMC NCT00365105
===Breast cancer===
*Amgen 20050136: Stopeck AT, Lipton A, Body JJ, Steger GG, Tonkin K, de Boer RH, Lichinitser M, Fujiwara Y, Yardley DA, Viniegra M, Fan M, Jiang Q, Dansey R, Jun S, Braun A. Denosumab compared with zoledronic acid for the treatment of bone metastases in patients with advanced breast cancer: a randomized, double-blind study. J Clin Oncol. 2010 Dec 10;28(35):5132-9. Epub 2010 Nov 8. link to original article EuroPMC NCT00321464
*CALGB 70604: Himelstein AL, Foster JC, Khatcheressian JL, Roberts JD, Seisler DK, Novotny PJ, Qin R, Go RS, Grubbs SS, O'Connor T, Velasco MR Jr, Weckstein D, O'Mara A, Loprinzi CL, Shapiro CL. Effect of Longer-Interval vs Standard Dosing of Zoledronic Acid on Skeletal Events in Patients With Bone Metastases: A Randomized Clinical Trial. JAMA. 2017 Jan 3;317(1):48-58. link to original article link to PMC article EuroPMC NCT00869206
*OPTIMIZE-2: Hortobagyi GN, Van Poznak C, Harker WG, Gradishar WJ, Chew H, Dakhil SR, Haley BB, Sauter N, Mohanlal R, Zheng M, Lipton A. Continued Treatment Effect of Zoledronic Acid Dosing Every 12 vs 4 Weeks in Women With Breast Cancer Metastatic to Bone: The OPTIMIZE-2 Randomized Clinical Trial. JAMA Oncol. 2017 Jul 1;3(7):906-912. link to original article link to PMC article EuroPMC NCT00320710
===Multiple myeloma===
* MRC Myeloma IX: Morgan GJ, Davies FE, Gregory WM, Cocks K, Bell SE, Szubert AJ, Navarro-Coy N, Drayson MT, Owen RG, Feyler S, Ashcroft AJ, Ross F, Byrne J, Roddie H, Rudin C, Cook G, Jackson GH, Child JA; National Cancer Research Institute Haematological Oncology Clinical Study Group. First-line treatment with zoledronic acid as compared with clodronic acid in multiple myeloma (MRC Myeloma IX): a randomised controlled trial. Lancet. 2010 Dec 11;376(9757):1989-99. Epub 2010 Dec 3. link to original article link to PMC article EuroPMC
*CALGB 70604: Himelstein AL, Foster JC, Khatcheressian JL, Roberts JD, Seisler DK, Novotny PJ, Qin R, Go RS, Grubbs SS, O'Connor T, Velasco MR Jr, Weckstein D, O'Mara A, Loprinzi CL, Shapiro CL. Effect of Longer-Interval vs Standard Dosing of Zoledronic Acid on Skeletal Events in Patients With Bone Metastases: A Randomized Clinical Trial. JAMA. 2017 Jan 3;317(1):48-58. link to original article link to PMC article EuroPMC NCT00869206
*Amgen 20090482: Raje N, Terpos E, Willenbacher W, Shimizu K, García-Sanz R, Durie B, Legieć W, Krejčí M, Laribi K, Zhu L, Cheng P, Warner D, Roodman GD. Denosumab versus zoledronic acid in bone disease treatment of newly diagnosed multiple myeloma: an international, double-blind, double-dummy, randomised, controlled, phase 3 study. Lancet Oncol. 2018 Mar;19(3):370-381. Epub 2018 Feb 9. link to original article EuroPMC NCT01345019
===Prostate cancer===
*Amgen 20050103: Fizazi K, Carducci M, Smith M, Damião R, Brown J, Karsh L, Milecki P, Shore N, Rader M, Wang H, Jiang Q, Tadros S, Dansey R, Goessl C. Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study. Lancet. 2011 Mar 5;377(9768):813-22. Epub 2011 Feb 25. link to original article link to PMC article EuroPMC NCT00321620
*CALGB 70604: Himelstein AL, Foster JC, Khatcheressian JL, Roberts JD, Seisler DK, Novotny PJ, Qin R, Go RS, Grubbs SS, O'Connor T, Velasco MR Jr, Weckstein D, O'Mara A, Loprinzi CL, Shapiro CL. Effect of Longer-Interval vs Standard Dosing of Zoledronic Acid on Skeletal Events in Patients With Bone Metastases: A Randomized Clinical Trial. JAMA. 2017 Jan 3;317(1):48-58. link to original article link to PMC article EuroPMC NCT00869206
==Dosing==
*CALGB 70604 results, published as abstract only, demonstrate non-inferiority of 3-month dosing vs. monthly dosing.Himelstein, Andrew Louis, Qin, Rui, Novotny, Paul J., Seisler, Drew K., Khatcheressian, James L., Roberts, John D., Grubbs, Stephen S., O'Connor, Tracey, Weckstein, Douglas, Loprinzi, Charles L., Shapiro, Charles L. CALGB 70604 (Alliance): A randomized phase III study of standard dosing vs. longer interval dosing of zoledronic acid in metastatic cancer. J Clin Oncol (Meeting Abstracts) 2015 33: 9501
*OPTIMIZE-2 demonstrated non-inferiority between every 4 week and every 12 week dosing in metastatic breast cancer.Hortobagyi GN, Van Poznak C, Harker WG, Gradishar WJ, Chew H, Dakhil SR, Haley BB, Sauter N, Mohanlal R, Zheng M, Lipton A. Continued Treatment Effect of Zoledronic Acid Dosing Every 12 vs 4 Weeks in Women With Breast Cancer Metastatic to Bone: The OPTIMIZE-2 Randomized Clinical Trial. JAMA Oncol. 2017 Jul 1;3(7):906-912. link to original article link to PMC article EuroPMC
==Patient drug information==
*Zoledronic acid (Zometa) patient drug information (Chemocare)Zoledronic acid (Zometa) patient drug information (Chemocare)
*Brief patient counseling information can be found in the Zoledronic acid (Zometa) package insert
*Zoledronic acid (Zometa) patient drug information (UpToDate)Zoledronic acid (Zometa) patient drug information (UpToDate)
==Management checklist==
*Basic metabolic panel (BMP) including creatinine and calcium, albumin (to calculate corrected calcium), phosphorus, vitamin D 25, bone density, calcium & vitamin D supplementation, dental exam/dental health
==Also known as==
*Generic names: acido zoledronico, zoledronate
*Brand names: Aclasta, Blaztere, Cytozol, Reclast, Servycal, Zobone, Zoldonat, Zomera, Zometa, Zyfoss
==References==
Category:Drugs
Category:Intravenous medications
Category:Bisphosphonates
Category:FDA approved in 2001
Category:PMDA approved in 2004
Category:WHO Essential Cancer Medicine