Details of the Drug Combinations

General Information of This Drug (ID: DMIXC7G)

• Drug Name: Zoledronate (DMIXC7G)
• Synonyms: Aclasta; Reclast; ZOL; Zometa; Novartis brand of zoledronic acid; Zoledronic acid; Zometa Concentrate; Bisphosphonate 3; CGP 42446; CGP 42446A; Aclasta (TN); CGP 42'446; CGP-42446; KS-1132; Reclast (TN); Zoledronic acid (INN); Zoledronic acid [USAN:INN]; Zomera (TN); Zometa (Novartis); Zometa (TN); CGP-42'446; Zometa, Zomera, Aclasta and Reclast, Zoledronic Acid; [1-hydroxy-2-(1H-imidazol-1-yl)ethane-1,1-diyl]bis(phosphonic acid); (1-Hydroxy-2-imidazol-1-ylethylidene)diphosphonic acid; (1-hydroxy-2-(1H-imidazol-1-yl)ethylidene)bisphosphonic acid; (1-hydroxy-2-imidazol-1-yl-1-phosphonoethyl)phosphonic acid; (1-hydroxy-2-imidazol-1-yl-phosphonoethyl)phosphonic acid monohydrate; 2-(imidazol-1-yl)-1-hydroxyethane-1,1-diphosphonic acid; 2-(imidazol-1-yl)-1-hydroxyethylidene-1,1-bisphosphonic acid

Indication

Adenocarcinoma; ICD 11: 2D40; Status: Approved [1]; Bone giant cell tumor; ICD 11: N.A.; Status: Approved [2]; Bone Paget disease; ICD 11: N.A.; Status: Approved [3]; Hypercalcaemia; ICD 11: 5B91.0; Status: Approved [4]; Multiple sclerosis; ICD 11: 8A40; Status: Approved [5]; Osteoporosis; ICD 11: FB83.0; Status: Approved [6]

• Therapeutic Class: Bone Density Conservation Agents
• Drug Type: Small molecular drug

List of Combinatorial Drugs (CBD) Containing This Drug

13 Investigative Drug Combination(s) Consisting of This drug

Normalized Drug Combination Synergy Score

Synergy scores were normalized using Min-Max Scaling to facilitate visual comparisons.

DrugCom Name	DrugCom ID	Component Drug	Indication	REF
MK-5108 + Zoledronate	DCXFU95	MK-5108	Ewing sarcoma (Cell Line: TC-71)	[7]
MK-5108 + Zoledronate	DCJ6CUY	MK-5108	Ewing sarcoma (Cell Line: EW-8)	[7]
MK-5108 + Zoledronate	DCUBBX3	MK-5108	Embryonal rhabdomyosarcoma (Cell Line: Rh36)	[8]
MK-5108 + Zoledronate	DCVHUDQ	MK-5108	Hodgkin lymphoma (Cell Line: U-HO1)	[8]
Zoledronate + MK-1775	DCG1XF8	MK-1775	Ewing sarcoma (Cell Line: TC-71)	[7]
Zoledronate + Olaparib	DCPG2ZB	Olaparib	Ewing sarcoma (Cell Line: TC-71)	[7]
Zoledronate + Olaparib	DCHFG29	Olaparib	Ewing sarcoma (Cell Line: EW-8)	[7]
Zoledronate + Ruxolitinib	DC5OO7T	Ruxolitinib	Hodgkin lymphoma (Cell Line: HDLM-2)	[8]
Zoledronate + Ruxolitinib	DC6J1BT	Ruxolitinib	Hodgkin lymphoma (Cell Line: L-428)	[8]
Zoledronate + Ruxolitinib	DCKE48P	Ruxolitinib	Hodgkin lymphoma (Cell Line: L-1236)	[8]
Zoledronate + MK-1775	DCWZBEB	MK-1775	Embryonal rhabdomyosarcoma (Cell Line: Rh36)	[8]
Zoledronate + MK-1775	DCSL34J	MK-1775	Hodgkin lymphoma (Cell Line: U-HO1)	[8]
Zoledronate + Olaparib	DC89QRF	Olaparib	Hodgkin lymphoma (Cell Line: U-HO1)	[8]

14 Clinical Trial Drug Combination(s) Consisting of This drug

DrugCom Name	DrugCom ID	Component Drug	Indication	REF
Atorvastatin + Zoledronate	DCBINCJ	Atorvastatin	Kidney Cancer	[9]
Ifosfamide + Zoledronate	DC9WUO6	Ifosfamide	Osteosarcoma	[10]
Letrozole + Zoledronate	DCIMZA7	Letrozole	Breast Cancer	[11]
Letrozole + Zoledronate	DC61NWM	Letrozole	Breast Neoplasms	[12]
Letrozole + Zoledronate	DCVIW9B	Letrozole	Breast Cancer	[13]
Leuprolide + Zoledronate	DCF8M22	Leuprolide	Prostate Cancer	[14]
Pamidronate + Zoledronate	DCBVMXD	Pamidronate	Multiple Myeloma and Plasma Cell Neoplasm	[15]
Zoledronate + Teriparatide	DC2G1YP	Teriparatide	Osteoporosis	[16]
Zoledronate + Anastrozole	DCFSGGI	Anastrozole	Breast Cancer	[17]
Zoledronate + Tamoxifen	DCR04IN	Tamoxifen	Breast Cancer	[17]
Zoledronate + Dasatinib	DCTIUK9	Dasatinib	Breast Cancer	[18]
Dexamethasone + Zoledronate	DCRMF2D	Dexamethasone	Multiple Myeloma	[19]
Docetaxel + Zoledronate	DCI3EHU	Docetaxel	Hormone-Refractory Prostate Cancer	[20]
Enzalutamide + Zoledronate	DC756M4	Enzalutamide	Prostate Cancer	[21]

References

• [1] In vitro cytotoxicity of zoledronate (nitrogen-containing bisphosphonate: NBP) and/or etidronate (non-NBP) in tumour cells and periodontal cells. Arch Oral Biol. 2013 Jun;58(6):628-37.
• [2] Giant Cell Tumor of Bone: Review of Current Literature, Evaluation, and Treatment Options. J Knee Surg. 2019 Apr;32(4):331-336.
• [3] Paget's Disease of Bone: Diagnosis and Treatment. Am J Med. 2018 Nov;131(11):1298-1303.
• [4] Current and future treatments of bone metastases. Expert Opin Emerg Drugs. 2008 Dec;13(4):609-27.
• [5] Clinical, radiographic, and biochemical characterization of multiple myeloma patients with osteonecrosis of the jaw. Clin Cancer Res. 2008 Apr 15;14(8):2387-95.
• [6] AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS/AMERICAN COLLEGE OF ENDOCRINOLOGY CLINICAL PRACTICE GUIDELINES FOR THE DIAGNOSIS AND TREATMENT OF POSTMENOPAUSAL OSTEOPOROSIS-2020 UPDATE. Endocr Pract. 2020 May;26(Suppl 1):1-46.
• [7] Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
• [8] Loss of function mutations in VARS encoding cytoplasmic valyl-tRNA synthetase cause microcephaly, seizures, and progressive cerebral atrophy.Hum Genet. 2018 Apr;137(4):293-303. doi: 10.1007/s00439-018-1882-3. Epub 2018 Apr 24.
• [9] ClinicalTrials.gov (NCT00490698) Zoledronate With Atorvastatin in Renal Cell Carcinoma
• [10] ClinicalTrials.gov (NCT00691236) Evaluation of Zoledronic Acid as a Single Agent or as an Adjuvant to Chemotherapy in High Grade Osteosarcoma
• [11] ClinicalTrials.gov (NCT00412022) HOBOE: A Phase 3 Study of Adjuvant Triptorelin and Tamoxifen, Letrozole, or Letrozole and Zoledronic Acid in Premenopausal Patients With Breast Cancer.
• [12] ClinicalTrials.gov (NCT00050011) Zoledronic Acid - Letrozole Adjuvant Synergy Trial (ZFAST) - Cancer Treatment Related Bone Loss in Postmenopausal Women With Estrogen Receptor Positive and/or Progesterone Receptor Positive Breast Cancer Receiving Adjuvant Hormonal Therapy
• [13] ClinicalTrials.gov (NCT00107263) Zoledronate in Preventing Bone Loss in Postmenopausal Women Who Are Receiving Letrozole for Stage I, Stage II, or Stage IIIA Breast Cancer
• [14] ClinicalTrials.gov (NCT00193856) RADAR Trial - Randomised Androgen Deprivation and Radiotherapy
• [15] ClinicalTrials.gov (NCT00482378) Samarium Sm 153 Lexidronam Pentasodium Combined With Zoledronic Acid or Pamidronate in Treating Patients With Relapsed or Refractory Multiple Myeloma and Bone Pain
• [16] ClinicalTrials.gov (NCT00439244) Efficacy Study of Zoledronic Acid and Teriparatide Combination Therapy in Women With Osteoporosis
• [17] ClinicalTrials.gov (NCT00295646) Tamoxifen Versus Anastrozole, Alone or in Combination With Zoledronic Acid
• [18] ClinicalTrials.gov (NCT00566618) Dasatinib in Combination With Zoledronic Acid for the Treatment of Breast Cancer With Bone Metastasis
• [19] ClinicalTrials.gov (NCT00972959) Effect of Combination of Bortezomib/Dexamethasone/Zoledronic Acid on Bone Disease in Patients With Multiple Myeloma Relapsed After 1-3 Prior Lines of Therapy
• [20] ClinicalTrials.gov (NCT00151073) Estramustine, Docetaxel and Zoledronate Treatment in Hormone-Refractory Adenocarcinoma of the Prostate
• [21] ClinicalTrials.gov (NCT03336983) Luteinizing Hormone-releasing Hormone Analogue and Enzalutamide +/- Zoledronic Acid in Prostate Cancer Patients