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Denosumab in advanced/unresectable giant-cell tumour of bone (GCTB): For how long?
- Source :
- European Journal of Cancer. 76:118-124
- Publication Year :
- 2017
- Publisher :
- Elsevier BV, 2017.
-
Abstract
- Background Giant-cell tumours of bone (GCTB) are RANK/RANK-ligand (RANKL) positive, aggressive and progressive osteolytic tumours. Denosumab, a RANKL inhibitor, was FDA-approved for adults and skeletally mature adolescents with unresectable GCTB or when surgical resection is likely to result in severe morbidity. Data on long-term toxicity and activity of denosumab monthly ‘GCTB-schedule’ (120 mg per 12/year, 1440 mg total dose/year) are lacking. Methods Patients with GCTB receiving denosumab, 120 mg on days 1, 8, 15, 29 and every 4 weeks thereafter, from 2006 to 2015 treated in two centres were included. Long-term toxicity was evaluated. Results Ninety-seven patients were identified. 43 patients underwent resection of the tumour with a median time on denosumab treatment of 12 months (range 6–45 months). Fifty-four patients had unresectable GCTB's (male/female 23/31, median age 35 years [range: 13–76 years], 26% presented with lung metastases, 31% had primary tumor located to the spine, 63% were relapsed after previous surgery) with a median time on denosumab of 54 months (9–115 months). In the unresectable GCTB group, tumour control and clinical benefits were observed in all patients undergoing denosumab, whereas 40% of patients discontinuing denosumab had tumour progression after a median of 8 months (range 7–15 months). Adverse events Overall, six (6%) patients developed osteonecrosis of jaw (ONJ): 1/43 (2%) in the resectable group, 5/54 (9%) in the unresectable group, with a 5-year ONJ-free survival of 92% (95% CI 84–100). Only patients with prolonged treatment experienced mild peripheral neuropathy (6/54, 11%), skin rash (5/54, 9%), hypophosphataemia (2/54, 4%) and atypical femoral fracture (2/54, 4%). Conclusions Prolonged treatment with denosumab has sustained activity in GCTB, with a mild toxicity profile. The dose-dependent toxicity observed recommends a careful and strict monitoring of patients who need prolonged treatment. Decreased dose-intensity schedules should be further explored in unresectable GCTB.
- Subjects :
- Male
Cancer Research
Lung Neoplasms
Time Factors
Receptor activator of nuclear factor κB ligand
Cohort Studies
0302 clinical medicine
GCTB
Giant Cell Tumor of Bone
Bone Density Conservation Agents
Femoral Neoplasms
Middle Aged
Primary tumor
Rash
Radius
medicine.anatomical_structure
Denosumab
Oncology
030220 oncology & carcinogenesis
Toxicity
Disease Progression
Bisphosphonate-Associated Osteonecrosis of the Jaw
Female
medicine.symptom
medicine.drug
Adult
Sacrum
medicine.medical_specialty
Adolescent
ONJ
Skull Neoplasms
Bone Neoplasms
Young Adult
03 medical and health sciences
Ischium
medicine
Giant-cell tumour of the bone
Humans
Adverse effect
Aged
Retrospective Studies
Spinal Neoplasms
Lung
Dose-Response Relationship, Drug
Tibia
business.industry
medicine.disease
Surgery
Peripheral neuropathy
Giant cell
business
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 09598049
- Volume :
- 76
- Database :
- OpenAIRE
- Journal :
- European Journal of Cancer
- Accession number :
- edsair.doi.dedup.....24eff198fbe263c96faf179303ba4e51