Preclinical and clinical aspects on the use of amifostine as chemoprotector in neuroblastoma patients.
BACKGROUND
In several studies in adults, amifostine (WR-2721) and its active metabolite WR-1065 have shown protection against myelo- and nephrotoxicity of chemotherapeutic agents without compromising cytotoxic efficacy to the tumor.


METHODS
In the present study, the effect of amifostine and WR-1065 on neuroblastoma tumor growth and its protective potential for hematotoxicity were investigated. Neither amifostine nor WR-1065 reduced the cytotoxic effect of six drugs commonly used for this tumor when tested on neuroblastoma cells in vitro.


RESULTS
In mice carrying human xeno-transplanted neuroblastoma, tumor growth and antitumor activity of chemotherapy were unaffected by amifostine. In addition, hematotoxicity of alkylators was relieved in some cases. In patients with neuroblastoma, amifostine only slightly reduced bone marrow toxicity and was highly emetogenic.


CONCLUSIONS
Therefore, amifostine warrants further investigation before its widespread clinical use in the treatment of children with neuroblastoma.
Fulda
S
S
Children's Hospital, University of Cologne, Germany.
Fichtner
I
I
Hero
B
B
Berthold
F
F
D000293:Adolescent; D004999:Amifostine / Q000009:adverse effects / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use / Q000633:toxicity; D001855:Bone Marrow Diseases / Q000139:chemically induced / Q000517:prevention & control*; D016190:Carboplatin / Q000009:adverse effects* / Q000627:therapeutic use; D002455:Cell Division / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D002945:Cisplatin / Q000627:therapeutic use / Q000633:toxicity; D018592:Cross-Over Studies; D003520:Cyclophosphamide / Q000627:therapeutic use / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000627:therapeutic use / Q000633:toxicity; D004347:Drug Interactions; D005047:Etoposide / Q000627:therapeutic use / Q000633:toxicity; D006801:Humans; D007069:Ifosfamide / Q000627:therapeutic use / Q000633:toxicity; D008624:Mercaptoethylamines / Q000009:adverse effects / Q000627:therapeutic use*; D051379:Mice; D008819:Mice, Nude; D009447:Neuroblastoma / Q000188:drug therapy* / Q000473:pathology; D009503:Neutropenia / Q000139:chemically induced / Q000517:prevention & control; D011355:Prodrugs / Q000009:adverse effects / Q000627:therapeutic use*; D012449:Safety; D013921:Thrombocytopenia / Q000139:chemically induced / Q000517:prevention & control; D017211:Treatment Failure; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014750:Vincristine / Q000627:therapeutic use / Q000633:toxicity; D014839:Vomiting / Q000139:chemically induced; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D008624:Mercaptoethylamines; D011355:Prodrugs; C020174:N-(2-mercaptoethyl)-1,3-diaminopropane; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D016190:Carboplatin; D004999:Amifostine; D002945:Cisplatin; D007069:Ifosfamide