Efficacy and Tolerance Adjuvant High-Dose Thiotepa With Peripheral Stem Cell Rescue Associated With Conventional Chemotherapy in Children and Adults With Relapsed Osteosarcoma
Despite the absence of tumor registry, approximately 150 new cases of osteosarcoma are
reported each year in France (100 cases per year in children and 50 cases in adults), of
which 15 to 20% are metastatic. The standardized impact rate in the world population is
estimated at 3 per million inhabitants per year.
Further to the initial standard care, about 45% of the patients relapse within a median
interval of 20 months (range 3 months - 10 years).
Results of the OS94 study and of the investigation performed within the CRLCC indicate that
25 to 30 patients (children and adults) experience an osteosarcoma relapse each year in
Results of the five major published series indicate that the 5-year overall survival rate of
patients in first relapse is between 23 and 28%, with a median post-relapse survival of 10
to 17 months. Multiple relapse cases are also reported in the COSS study, with a median time
to second relapse of 0.8 year.
At present, there is no reference treatment for the standard care of osteosarcoma relapse in
Some recommendations have been given in the OS94 protocol, but they are generally not
followed or they are implemented in a heterogeneous manner.
Thiotepa (N N' N'' triethylenethiophosphoramide), an alkylating agent of the chemical family
of ethylene-imines, is known for its antitumor effect in a number of malignant tumors.
Its efficacy in osteosarcoma has been reported in the literature. A retrospective study of
the SFCE (French Society for Childhood Cancer, results not yet published) in 45 patients
presenting with refractory osteosarcoma or relapse has shown a radiological reaction rate of
Moreover, a preliminary investigation performed by the CLB in 2007 within the framework of
the SFCE study explored all relapse cases diagnosed between the beginning of 2004 and the
end of 2006. Results showed that about 35% of the patients with osteosarcoma relapses are
treated with high-dose thiotepa while the efficacy and tolerance of this therapeutic
strategy have never been assessed.
Altogether, these results led the SFCE osteosarcoma group to propose the evaluation of the
efficacy and tolerance of this high-dose thiotepa chemotherapy within a clinical trial and
to include the drug in the standard care of osteosarcoma in relapse.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Estimate the overall survival rate
Perrine MAREC-BÉRARD, Dr
Institut d'Hématologie et d'Oncologie Pédiatrique (IHOP) - CLB
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)