Effect of amifostine on neuroblastoma during high dose chemotherapy: in vivo and in vitro investigations.
Amifostine (Ethyol, WR-2721) has been clinically used in combination with high dose therapy of neuroblastoma stage 4 with melphalan, carboplatin and VP-16 in 14 patients. The amifostine group was compared to a historical control group of 24 comparably-treated patients. There were no significant differences regarding the time of hematological recovery, the duration of hospitalization, the duration of antibiotic treatment and the extent of renal toxicity. However, in contrast to four patients of the control group, no patient in the amifostine group developed such severe mucositis that artificial ventilation became necessary. Pretreatment of neuroblastoma cell lines for 30 minutes with amifostine and the free thiol(WR-1065) did not reduce the cytotoxic effects of melphalan, carboplatin and VP-16. Evidence was obtained that the uptake of the activated thiol could be achieved by a polyamine transporter. Taken together, the data do not support the use of amifostine in high dose chemotherapy of neuroblastoma prior to autologous stem cell transplantation. However, amifostine may be more effective in conventional neuroblastoma therapy where protection of bone marrow stem cells is necessary.
Renner
S
S
Department of Hematology and Oncology, University Children Hospital, Hoppe-Seyler-Str. 1, D-72076 Tübingen, Germany.
Krümpelmann
S
S
Bruchelt
G
G
Wiesinger
H
H
Niethammer
D
D
Klingebiel
T
T
D004999:Amifostine / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001663:Bilirubin / Q000097:blood; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D016022:Case-Control Studies; D002648:Child; D003404:Creatinine / Q000378:metabolism; D004347:Drug Interactions; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007249:Inflammation / Q000139:chemically induced; D008558:Melphalan / Q000008:administration & dosage / Q000009:adverse effects; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D020545:Respiratory Mucosa / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D014839:Vomiting / Q000139:chemically induced
D005047:Etoposide; D003404:Creatinine; D016190:Carboplatin; D004999:Amifostine; D008558:Melphalan; D001663:Bilirubin