Combination of zoledronic Acid and targeted therapy is active but may induce osteonecrosis of the jaw in patients with metastatic renal cell carcinoma

J Oral Maxillofac Surg. 2013 Sep;71(9):1532-40. doi: 10.1016/j.joms.2013.03.019. Epub 2013 May 1.

Abstract

Purpose: To investigate the efficacy and safety of zoledronic acid (ZA) combined with targeted therapy (TT).

Materials and methods: A retrospective study was performed in patients with metastatic renal cell carcinoma treated with ZA and TT.

Results: Twenty-one patients received ZA and TT to prevent skeletal-related events and no pretherapy oral and maxillofacial (OM) examination (cohort A). Six patients (29%) developed osteonecrosis of the jaw (ONJ), which was observed only in patients receiving sunitinib and ZA. Sixteen patients received TT and ZA for hypercalcemia and no pretherapy OM examination (cohort B). In these patients, no ONJ was observed. Nine patients received ZA and TT and pretherapy OM examination (cohort C). One patient (11%) developed ONJ during sunitinib and ZA treatment. Mean skeletal morbidity rates were 0.8 for cohort A and 1.2 for cohort C. In the combined cohort (A plus C; n = 30), 47% developed skeletal-related events, 7% pathologic fracture, 7% medullary compression, and 37% progression of bone metastases. Patients who developed ONJ had a significantly improved median survival of 31.6 months compared with 14.5 months in patients without ONJ (P = .039).

Conclusion: The combination of ZA and TT resulted in high, clinically meaningful activity. ONJ may be exacerbated by concomitant ZA and sunitinib. Regular OM examinations before and during treatment are recommended.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Angiogenesis Inhibitors / therapeutic use
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antineoplastic Agents / therapeutic use*
  • Bevacizumab
  • Bisphosphonate-Associated Osteonecrosis of the Jaw / etiology*
  • Bone Density Conservation Agents / adverse effects
  • Bone Density Conservation Agents / therapeutic use*
  • Bone Neoplasms / drug therapy
  • Bone Neoplasms / secondary*
  • Carcinoma, Renal Cell / drug therapy
  • Carcinoma, Renal Cell / secondary*
  • Cohort Studies
  • Diphosphonates / adverse effects
  • Diphosphonates / therapeutic use*
  • Everolimus
  • Female
  • Follow-Up Studies
  • Fractures, Spontaneous / etiology
  • Humans
  • Imidazoles / adverse effects
  • Imidazoles / therapeutic use*
  • Indazoles
  • Indoles / therapeutic use
  • Interleukin-2 / therapeutic use
  • Kidney Neoplasms / pathology
  • Male
  • Middle Aged
  • Molecular Targeted Therapy / methods*
  • Niacinamide / analogs & derivatives
  • Niacinamide / therapeutic use
  • Phenylurea Compounds / therapeutic use
  • Pyrimidines / therapeutic use
  • Pyrroles / therapeutic use
  • Radiography, Panoramic
  • Retrospective Studies
  • Sirolimus / analogs & derivatives
  • Sirolimus / therapeutic use
  • Sorafenib
  • Spinal Cord Compression / etiology
  • Sulfonamides / therapeutic use
  • Sunitinib
  • Survival Rate
  • Zoledronic Acid

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Bone Density Conservation Agents
  • Diphosphonates
  • Imidazoles
  • Indazoles
  • Indoles
  • Interleukin-2
  • Phenylurea Compounds
  • Pyrimidines
  • Pyrroles
  • Sulfonamides
  • Niacinamide
  • Bevacizumab
  • temsirolimus
  • Zoledronic Acid
  • pazopanib
  • Everolimus
  • Sorafenib
  • Sunitinib
  • Sirolimus