title: Tandem high-dose chemotherapy strategy as first-line treatment of primary disseminated multifocal Ewing sarcomas in children, adolescents and young adults.
abstract: The prognosis of primary disseminated multifocal metastatic Ewing's sarcoma (PDMES) is poor even if a slight improvement has been achieved with high-dose alkylating agent-containing chemotherapy. To enhance treatment efficacy, we assessed the feasibility, safety and efficacy of a tandem high-dose chemotherapy (HDC) regimen. In a single institution, patients with PDMES received six courses of vincristine/ifosfamide/doxorubicin/etoposide induction therapy, followed by high-dose thiotepa, and then melphalan-busulfan, 8 weeks apart. Surgical resection of primary tumour was carried out between the two HDC regimens and 70 days after the last HDC regimen for post-operative radiotherapy or irradiation alone. From October 2002 to 2009, 13 of the 18 consecutive patients with PDMES (72%) received the full treatment programme. The other five patients experienced early progression and died. Among the 13 patients, 11 relapsed after the end of the treatment programme within 6 months (2.2-11.9) from end of therapy. Only two patients are still alive in first complete remission after 9 years. The 3-year event-free survival (EFS) and overall survival (OS) rates were 11 and 22%, respectively. The median EFS and OS duration from the diagnosis were 13.4 and 17.3 months, respectively. Neither major complications nor treatment-related death occurred. The tandem-HDC regimen was feasible, with expected side effects, but it did not improve the outcome of patients with PDMES.
authors.affiliation: Département de cancérologie de l'enfant et de l'adolescent, Gustave Roussy, Villejuif, France.
authors.forename: S
authors.initials: S
authors.lastname: Loschi
authors.affiliation: Département de cancérologie de l'enfant et de l'adolescent, Gustave Roussy, Villejuif, France.
authors.forename: C
authors.initials: C
authors.lastname: Dufour
authors.affiliation: Département de cancérologie de l'enfant et de l'adolescent, Gustave Roussy, Villejuif, France.
authors.forename: O
authors.initials: O
authors.lastname: Oberlin
authors.affiliation: Département de biostatistiques, Gustave Roussy, Villejuif, France.
authors.forename: G
authors.initials: G
authors.lastname: Goma
authors.affiliation: Département de cancérologie de l'enfant et de l'adolescent, Gustave Roussy, Villejuif, France.
authors.forename: D
authors.initials: D
authors.lastname: Valteau-Couanet
authors.affiliation: Département de cancérologie de l'enfant et de l'adolescent, Gustave Roussy, Villejuif, France.
authors.forename: N
authors.initials: N
authors.lastname: Gaspar
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D059248:Chemoradiotherapy / Q000379:methods*; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008297:Male; D012512:Sarcoma, Ewing / Q000401:mortality* / Q000628:therapy*; D015996:Survival Rate; D013852:Thiotepa / Q000008:administration & dosage; D014750:Vincristine / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D013852:Thiotepa; D007069:Ifosfamide