International Journal of
Radiation Oncology biology
physics
www.redjournal.org
Clinical Investigation
High-Dose Hypofractionated Radiation Therapy for Noncompressive Vertebral Metastases in Combination With Zoledronate: A Phase 1 Study Baptiste Pichon, MD,* Loı¨c Campion, MD,y Gre´gory Delpon, PhD,z,x Franc¸ois Thillays, MD, MSc,* Christian Carrie, MD,k Patrice Cellier, MD,{ Pascal Pommier, MD, PhD,k Ce´cile Laude, MD,k Augustin Mervoyer, MD,* Hadji Hamidou, MD,{ Marc-Andre´ Mahe´, MD, PhD,* and Ste´phane Supiot, MD, PhD*,x Departments of *Radiation Oncology, yBiostatistics, and zMedical Physics, ICO Cancer Center, SaintHerblain; xCRCNA, Inserm U892, CNRS UMR 6299, Nantes; kDepartment of Radiation Oncology, Le´on Be´rard Center, Lyon; and {Department of Radiation Oncology, ICO Cancer Center, Angers, France Received Mar 14, 2016, and in revised form Jul 12, 2016. Accepted for publication Jul 25, 2016.
Summary This study aimed to evaluate the tolerability of zoledronate in association with hypofractionated stereotactic radiation therapy (HSRT) for vertebral metastases. 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.
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; PZ.0125)
Reprint requests to: Ste´phane Supiot, MD, PhD, Department of Radiation Oncology, ICO Cancer Center, Saint-Herblain, France. Tel: (þ33) 240679900; E-mail:
[email protected] Presented at the 57th Annual Meeting of the American Society for Radiation Oncology, San Antonio, TX, Oct 18-21, 2015.
Int J Radiation Oncol Biol Phys, Vol. 96, No. 4, pp. 840e847, 2016 0360-3016/$ - see front matter Ó 2016 Published by Elsevier Inc. http://dx.doi.org/10.1016/j.ijrobp.2016.07.027
Supported by bourse Novartis du Groupe Europe´en d’Etudes des Me´tastases Osseuses, Ligue contre le cancer (10/210: Plate-Forme de Recherche Clinique du Cance´ropoˆle Grand-Ouest). Conflict of interest: none. Supplementary material for this article can be found at www.redjournal.org.
Volume 96 Number 4 2016
Phase 1 study of SBRT and zoledronate
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