Use of amifostine in the therapy of osteosarcoma in children and adolescents.
Amifostine protects normal tissue from the cytotoxic damage induced by radiation and chemotherapy. In this study, 39 consecutive newly diagnosed children with osteosarcoma were assessed; 20 received amifostine and 19 did not. The chemotherapy regimen included an induction phase of three cycles of cisplatin (100 mg/m2), carboplatin (500 mg/m2), and doxorubicin (60 mg/m2), followed by surgery. Alternating cycles of cisplatin/ifosfamide (9 mg/m2), ifosfamide/doxorubicin, carboplatin/doxorubicin, and ifosfamide/carboplatin were administered every 3 weeks to complete 26 weeks of treatment. Amifostine was administered 15 minutes before the infusions of cisplatin and carboplatin in a total of 193 infusions. Side effects during infusions and renal, hearing, and bone marrow toxicities were evaluated and compared between the two groups. Hypotension was observed in 28 (14.5%) infusions. No patient required discontinuation of therapy. Fewer than two episodes of vomiting occurred in 130 (71%) infusions and two to five episodes occurred in 51 (28%) infusions, and no patient had grade 4 toxicity. There was no difference between the two groups regarding renal toxicity (creatinine clearance). Neutropenia and leukopenia were significantly less frequent in the amifostine group. No difference was observed in platelet and hearing toxicities. Amifostine was well tolerated in doses of 740 mg/m2 in children and adolescents, and myelotoxicity was less severe in the amifostine group. This was a pilot study for further evaluation in a larger randomized trial.
Petrilli
Antonio Sergio
AS
Pediatric Oncology Institute, Department of Pediatrics-Escola Paulista de Medicina, Universidade Federal de São Paulo, SP, Brazil. iopepm@dialdata.com.br
Oliveira
Delma Tostes
DT
Ginani
Valeria Cortez
VC
Kechichian
Rita
R
Dishtchekenian
Andrea
A
Filho
Werthon de Medeiros Roque
Wde M
Tanaka
Cristiana
C
Dias
Carlo Gonçalves
CG
Latorre
Maria do Rosário Dias de Oliveira
Mdo R
Brunetto
Algemir Lunardi
AL
Cardoso
Hedilene
H
Almeida
Maria Teresa
MT
de Camargo
Beatriz
B
D000293:Adolescent; D000328:Adult; D004999:Amifostine / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects; D007970:Leukopenia / Q000139:chemically induced; D008297:Male; D009503:Neutropenia / Q000139:chemically induced; D012516:Osteosarcoma / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D010865:Pilot Projects; D011837:Radiation-Protective Agents / Q000627:therapeutic use*; D016896:Treatment Outcome
D011837:Radiation-Protective Agents; D004317:Doxorubicin; D016190:Carboplatin; D004999:Amifostine; D002945:Cisplatin; D007069:Ifosfamide