Nonmetastatic Ewing family tumors: high-dose chemotherapy with stem cell rescue in poor responder patients. Results of the Italian Sarcoma Group/Scandinavian Sarcoma Group III protocol.
BACKGROUND
High-dose chemotherapy (HDT) was added to conventional chemotherapy in Ewing sarcoma family tumor (EFT) patients, poor responders (PRs) to induction chemotherapy in order to improve their survival.


METHODS
Patients aged ≤40 years with nonmetastatic Ewing sarcoma (ES) received vincristine (V), doxorubicin (A), cyclofosfamide (C), actinomycin (Ac), ifosfamide (I) and etoposide (E) (VACAc-IE regimen) as induction chemotherapy. As maintenance treatment, good responders (GR) received nine cycles of VACAc-IE regimen. PRs received three cycles of VAC-IE, mobilizing cycle with CE and HDT with Busulfan and Melphalan with stem cell support.


RESULTS
Three hundred patients [median age 15 years (3-40 years)] entered the study. One patient refused local treatment, 242 (81%) underwent surgery [with radiotherapy (RT) in 80] and 57 (19%) RT alone. No toxic deaths were recorded. Overall GR were 146 (49%). Twenty-eight PR did not receive HDT. At a median follow-up of 64 months (21-116 months), 5-year overall and event-free survival (EFS) were 75% and 69%, respectively. Five-year EFS was 75% for GR, 72% for PR treated with HDT and 33% for PR who did not receive HDT.


CONCLUSIONS
High-dose therapy added to the VACA-IE regimen in PR patients is feasible and effective. Selected groups of patients with ES can benefit from HDT.
Department of Chemotherapy, Istituto Ortopedico Rizzoli, Bologna, Italy. Electronic address: stefano.ferrari@ior.it.
S
S
Ferrari
Oncology Department, The Norwegian Radium Hospital, Oslo, Norway.
K
K
Sundby Hall
Pediatric Oncology Division, Istituto Nazionale Tumori, Milan.
R
R
Luksch
Department of Medical Oncology, S.Maria delle Croci Hospital, Ravenna, Italy.
A
A
Tienghi
Department of Cancer Epidemiology, and Paediatric Oncology, Lund University Hospital, Lund, Sweden.
T
T
Wiebe
Department of Pediatric Oncology, Ospedale Regina Margherita, Torino.
F
F
Fagioli
Department of Cancer Epidemiology, and Paediatric Oncology, Lund University Hospital, Lund, Sweden.
T A
TA
Alvegard
Department of Pediatric Oncology, Ospedale Regina Margherita, Torino.
A
A
Brach Del Prever
Pediatric Oncology Division, Meyer Hospital, Firenze.
A
A
Tamburini
Department of Pathology, Istituto Ortopedico Rizzoli, Bologna.
M
M
Alberghini
Radiotherapy Unit, Istituto Nazionale Tumori, Milano.
L
L
Gandola
Department of Surgery, Istituto Ortopedico Rizzoli, Bologna.
M
M
Mercuri
Oncologic/Orthopaedic Surgery Division, Centro Traumatologico Ortopedico, Firenze.
R
R
Capanna
Oncologic/Orthopaedic Surgery, Istituto Gaetano Pini, Milan.
S
S
Mapelli
Department of Pediatric Oncology, University Hospital, Bologna.
A
A
Prete
Department of Pediatric Oncology, University Hospital, Padova.
M
M
Carli
Experimental Oncology Divisions, Department of Musculoskeletal Oncology, Istituto Ortopedico Rizzoli, Bologna.
P
P
Picci
Radiotherapy Division, University Hospital, Bologna, Italy.
E
E
Barbieri
Department of Chemotherapy, Istituto Ortopedico Rizzoli, Bologna, Italy.
G
G
Bacci
Oncology Department, The Norwegian Radium Hospital, Oslo, Norway.
S
S
Smeland
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000401:mortality / Q000628:therapy*; D002066:Busulfan / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000627:therapeutic use; D003609:Dactinomycin / Q000627:therapeutic use; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000627:therapeutic use; D005047:Etoposide / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000627:therapeutic use; D053208:Kaplan-Meier Estimate; D008297:Male; D008558:Melphalan / Q000627:therapeutic use; D019653:Myeloablative Agonists / Q000627:therapeutic use; D036102:Peripheral Blood Stem Cell Transplantation; D012512:Sarcoma, Ewing / Q000401:mortality / Q000628:therapy*; D014750:Vincristine / Q000627:therapeutic use; D055815:Young Adult
D019653:Myeloablative Agonists; D003609:Dactinomycin; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D002066:Busulfan; D008558:Melphalan; D007069:Ifosfamide