Melphalan combined with a carboplatin dose based on glomerular filtration rate followed by autologous stem cell rescue for children with solid tumours.
Carboplatin and melphalan are two drugs whose toxicity profile makes them suitable for use in high doses followed by stem cell rescue. We report the use of high-dose carboplatin, with the dose based on glomerular filtration rate (GFR), combined with melphalan followed by autologous stem cell rescue in children with advanced stage or chemoresistant solid tumours. Thirty children were treated. After multiagent induction chemotherapy before BMT, 13 were in CR, five in VGPR, 11 in PR and one had progressive disease. They received melphalan, 180 mg/m2 and carboplatin, followed by autologous stem cell rescue. The dose of carboplatin was varied by GFR rather than fixed by surface area. The dose given ranged from 0.7 to 2.6 g/m2. Haematological and gastrointestinal toxicities were severe. Life-threatening or fatal toxicity was attributable to opportunistic infection in two cases and regimen-related in two cases. Of the 30 patients, 15 are alive and 13 disease-free at 4-36 months post-BMT. This simple two-drug combination has been used as consolidation of initial remission for patients with high-risk tumours. The toxicity is severe but tolerable. Use of a carboplatin dose based on GFR should optimise effectiveness in patients with good renal function and avoid excessive toxicity where renal function is impaired.
Shaw
P J
PJ
Department of Oncology, Royal Alexandra Hospital for Children, Westmead, Sydney, Australia.
Pinkerton
C R
CR
Yaniv
I
I
D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001855:Bone Marrow Diseases / Q000139:chemically induced / Q000628:therapy; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D007239:Infections / Q000209:etiology / Q000401:mortality; D007674:Kidney Diseases / Q000139:chemically induced; D008297:Male; D008558:Melphalan / Q000008:administration & dosage / Q000009:adverse effects; D009369:Neoplasms / Q000188:drug therapy* / Q000401:mortality; D009447:Neuroblastoma / Q000188:drug therapy / Q000401:mortality; D016896:Treatment Outcome
D016190:Carboplatin; D008558:Melphalan