Ifosfamide and etoposide in childhood osteosarcoma. A phase II study of the French Society of Paediatric Oncology.
The aim of this phase II study was to determine the efficacy of high-dose ifosfamide with moderate dose etoposide in childhood osteosarcoma. From January 1992 to January 1995, 27 children (15 male, 12 female) with relapsed or refractory evaluable osteosarcoma were included in a phase II study of two courses of ifosfamide 3g/m2/day and etoposide 75 mg/m2/day for 4 days. Median age was 14 years (7-19 years). All but one had received high-dose methotrexate and doxorubicin as first-line treatment. 22 patients had previously received ifosfamide. This regimen was given as first-line in 1 patient, second-line in 23 and third-line in 3. Evaluable disease was lung metastases in 21 patients, local relapse in 5 and adenopathy in 1. There were six complete responses, seven partial responses, three minor responses, six stable disease and five progressive disease (including one mixed response). Response rate was 48% (95% confidence interval, 29-67%). Duration of response was not available (10 responding patients had other treatments). Response rate was equivalent in the subgroup of 22 patients who had previously received ifosfamide (4 CR, 6 PR). Among 3 patients who received the phase II regimen as third-line chemotherapy, there was 1 PR. All but 4 patients had a well tolerated grade 4 neutropenia. Transient mild confusion or seizures were each observed once. 5 patients are alive 15-31 months after the beginning of chemotherapy. This combination of drugs at this dosage has tolerable toxicity, is efficient and deserves evaluation in phase III studies.
Gentet
J C
JC
Fédération d'Oncologie Pédiatrique, Children's Hospital, Marseille, France.
Brunat-Mentigny
M
M
Demaille
M C
MC
Pein
F
F
Avet-Loiseau
H
H
Berger
C
C
De Lumley
L
L
Pacquement
H
H
Schmitt
C
C
Sariban
E
E
Pillon
P
P
Bernard
J L
JL
Kalifa
C
C
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy*; D002648:Child; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D012516:Osteosarcoma / Q000188:drug therapy*; D015996:Survival Rate; D016896:Treatment Outcome
D005047:Etoposide; D007069:Ifosfamide