A pilot study of addition of amifostine to melphalan, carboplatin, etoposide, and cyclophosphamide with autologous hematopoietic stem cell transplantation in pediatric solid tumors-A pediatric blood and marrow transplant consortium study.
Limited information is available regarding the use of amifostine in pediatric hematopoietic stem cell transplant (HSCT) patients. Melphalan, carboplatin, etoposide +/- cyclophosphamide is a commonly used preparatory regimen in pediatric solid tumor HSCT. Therefore, we decided to determine the feasibility of the addition of amifostine (750 mg/m b.i.d. x 4 d) to melphalan (200 mg/m), carboplatin (1200 mg/m), and etoposide (800 mg/m) (level 1) and escalating doses of cyclophosphamide (3000 mg/m and 3800 mg/m, levels 2 and 3, respectively) followed by autologous HSCT. Thirty-two patients with a variety of pediatric solid tumors were studied. Seventeen patients were accrued at level 1, 9 at level 2, and 6 at level 3. Major toxicities during the administration of the preparatory regimen were hypocalcemia, emesis, and hypotension. Hypocalcemia required aggressive calcium supplementation during the conditioning phase. No dose limiting toxicities were encountered at level 3. Amifostine at 750 mg/m b.i.d. for 4 days can be administered with a double alkylator regimen consisting of melphalan (200 mg/m), cyclophosphamide (up to 3800 mg/m), carboplatin (1200 mg/m), and etoposide (800 mg/m) with manageable toxicities.
Ozkaynak
M Fevzi
MF
Department of Pediatrics, Section of Hematology/Oncology, New York Medical College, Valhalla, NY 10595, USA. mehmet_ozkaynak@nymc.edu
Sahdev
Indira
I
Gross
Thomas G
TG
Levine
John E
JE
Cheerva
Alexandra C
AC
Richards
Michael K
MK
Rozans
Marta K
MK
Shaw
Peter J
PJ
Kadota
Richard P
RP
D000293:Adolescent; D000328:Adult; D004999:Amifostine / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation; D001859:Bone Neoplasms / Q000175:diagnosis / Q000628:therapy; D016190:Carboplatin / Q000008:administration & dosage; D016543:Central Nervous System Neoplasms / Q000175:diagnosis / Q000628:therapy; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D064420:Drug-Related Side Effects and Adverse Reactions; D005047:Etoposide / Q000008:administration & dosage; D005240:Feasibility Studies; D018380:Hematopoietic Stem Cell Transplantation; D006689:Hodgkin Disease / Q000175:diagnosis / Q000628:therapy; D006801:Humans; D006996:Hypocalcemia / Q000139:chemically induced / Q000473:pathology; D007680:Kidney Neoplasms / Q000175:diagnosis / Q000628:therapy; D008558:Melphalan / Q000008:administration & dosage; D009369:Neoplasms / Q000175:diagnosis / Q000628:therapy*; D009447:Neuroblastoma / Q000175:diagnosis / Q000628:therapy; D010865:Pilot Projects; D012008:Recurrence; D012307:Risk Factors; D012509:Sarcoma / Q000175:diagnosis / Q000628:therapy; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D009396:Wilms Tumor / Q000175:diagnosis / Q000628:therapy
D005047:Etoposide; D003520:Cyclophosphamide; D016190:Carboplatin; D004999:Amifostine; D008558:Melphalan