High-Dose Hypofractionated Radiation Therapy for Noncompressive Vertebral Metastases in Combination With Zoledronate: A Phase 1 Study

Int J Radiat Oncol Biol Phys. 2016 Nov 15;96(4):840-847. doi: 10.1016/j.ijrobp.2016.07.027. Epub 2016 Jul 30.


Introduction: Hypofractionated stereotactic radiation therapy (HSRT) for vertebral metastases gives good results in terms of local control but increases the risk of fracture in the treated volume. Preclinical and clinical studies have shown that zoledronate not only reduces the risk of fracture and stimulates osteoclastic remodeling but also increases the immune response and radiosensitivity. This study aimed to evaluate the tolerability and effectiveness of zoledronate in association with radiation therapy.

Patients and methods: We conducted a multicenter phase 1 study that combined HSRT (3 × 9 Gy) and zoledronate in patients with vertebral metastasis (NCT01219790). The principal objective was the absence of spinal cord adverse reactions at 1 year. The secondary objectives were acute tolerability, the presentation of a bone event, local tumor control, pain control, progression-free survival, and overall survival.

Results: Thirty patients (25 male, 5 female), median age 66 years, who were followed up for a median period of 19.2 months, received treatment for 49 vertebral metastases. A grade 3 acute mucosal adverse event occurred in 1 patient during the treatment and in 2 more at 1 month. No late neurologic adverse events were reported at 1 year. The mean pain scores diminished significantly at 1 month (1.35; P=.0125) and 3 months (0.77; P<.0001) compared with pain scores at study entry (2.49). Vertebral collapse in the irradiated zone occurred in 1 (2%) treated vertebra. Control of local disease was achieved in 94% of irradiated patients (3 local recurrences).

Conclusion: The combination of zoledronate and HSRT in the treatment of vertebral metastasis is well tolerated and seems to reduce the rate of vertebral collapse, effectively relieve pain, and achieve good local tumor control with no late neurologic adverse effects.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study

MeSH terms

  • Aged
  • Bone Density Conservation Agents / administration & dosage
  • Bone Density Conservation Agents / adverse effects*
  • Combined Modality Therapy
  • Diphosphonates / administration & dosage
  • Diphosphonates / adverse effects*
  • Disease-Free Survival
  • Female
  • Humans
  • Imidazoles / administration & dosage
  • Imidazoles / adverse effects*
  • Kaplan-Meier Estimate
  • Male
  • Pain Measurement
  • Radiation Dose Hypofractionation*
  • Radiosurgery / methods*
  • Spinal Cord / radiation effects
  • Spinal Neoplasms / mortality
  • Spinal Neoplasms / radiotherapy*
  • Spinal Neoplasms / secondary*
  • Zoledronic Acid


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