ABSTRACT
BACKGROUND: The objective of this study is to explore the off-label use of targeted therapies (TTs) for patients with osteosarcoma registered within the French Sarcoma Group--Bone Tumor Study Group (GSF-GETO) national registry. METHODS: All patients with an osteosarcoma, registered between January 1, 2009 and July 15, 2013 were analyzed. RESULTS: Twenty-nine patients with refractory relapsed osteosarcomas received 33 treatment lines of TTs. The median age at the beginning of treatment was 19 years (range 9-72). The median number of previous lines of chemotherapy was 3 (range 1-8). Before inclusion, 3 patients were in second complete remission, 26 were in progression for metastatic relapse. Twenty-three patients received sirolimus (in combination with cyclophosphamide for 18); 5, sunitinib; 4, sorafenib; and one, pazopanib. Stable disease was observed for 45.5% of patients (95% Confidence Interval (CI) [20-52.8]). The median Progression-Free Survival (PFS) was 3 months (95% CI [2-5.4]) for patients treated by sirolimus and 1.8 months (95% CI [1.3-2.8]) for patients receiving multi-targeted tyrosine kinase inhibitors; 6-month PFS 15%. The median Overall Survival (OS) was 6.8 months (95% CI [4.7-12.1]), and one-year OS was 24%. In a multivariate analysis, PFS was superior for patients receiving sirolimus compared to other TTs (Hazard Ratio (HR) = 2.7, 95% CI [1.05-7.1]). No toxic death was reported. Grade 3 and 4 toxicities were observed in 27 and 6% of cases respectively. CONCLUSION: Off-label TTs, especially sirolimus, reported benefit in the treatment of refractory osteosarcomas with an acceptable toxicity profile, including in pediatric population.
Subject(s)
Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Molecular Targeted Therapy , Off-Label Use , Osteosarcoma/drug therapy , Adolescent , Adult , Aged , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Child , Female , Follow-Up Studies , France , Humans , Male , Middle Aged , Molecular Targeted Therapy/methods , Neoplasm Grading , Neoplasm Recurrence, Local , Neoplasm Staging , Osteosarcoma/mortality , Osteosarcoma/pathology , Registries , Retreatment , Treatment Outcome , Young AdultABSTRACT
Thirty years ago, osteosarcoma of a limb meant amputation and death. Two years after diagnosis, 80% of the patients died from pulmonary metastases, despite early amputation. In 2002, more than 70% of these patients can be cured. Successful cure requires adequate and early management centered on en-bloc resection by a specialized surgeon, followed by a long, expensive, and adapted chemotherapy. The cornerstone is high-dose methotrexate. We present data accumulated over the last 30 years on the treatment of osteosarcoma and point out the fundamental steps of this success story.
