PMID- 11313680
OWN - NLM
STAT- MEDLINE
DCOM- 20010830
LR  - 20131121
IS  - 0268-3369 (Print)
IS  - 0268-3369 (Linking)
VI  - 27
IP  - 5
DP  - 2001 Mar
TI  - Pharmacodynamics of tandem high-dose melphalan with peripheral blood stem cell 
      transplantation in children with neuroblastoma and medulloblastoma.
PG  - 471-7
AB  - Repeated high-dose (HD) chemotherapy with peripheral blood stem cell (PBSC) 
      transplantation is a new modality aimed at increasing both the dose and its 
      intensity in the treatment of chemosensitive tumours. The aim of this study was 
      to evaluate the tolerance, pharmacokinetics (PK) and pharmacodynamics (PD) of HD 
      single-agent melphalan administered over two consecutive courses (C1 and C2) in 
      children. Twenty-one patients (10 girls) with a median age of 4.1 years (range 8 
      months-14 years) were entered into this study. Five had metastatic neuroblastoma 
      (NB) and 16 a cerebral primitive neuroectodermal tumour (PNET). Melphalan was 
      given at a dose of 100 mg/m(2) every 21 days. PBSCs were infused at a median 
      number of 2.98 x 10(6) CD34(+) cells/kg. Forty courses, ie 21 C1 and 19 C2, were 
      administered. Both courses were well tolerated. The median duration of ANC < 
      500/microl was 7 and 6 days after C1 and C2, respectively. Platelet recovery (not 
      mandatory to continue the HD strategy) was achieved in 52% of courses. GI 
      toxicity was mild to moderate. The melphalan AUC ranged from 177 to 475 microg 
      small middle dotmin/ml (no difference between C1 and C2). Prolonged neutropenia 
      was associated with a young age (P < 0.001) and a low amount of CFU-GM (P = 
      0.002). A long time to platelet recovery was associated with a high AUC (P = 
      0.004) and a young age (P = 0.02). Grade 1 or 2 GI toxicity was associated with a 
      high AUC (P = 0.015). Partial remission was observed in 11/14 patients with 
      measurable cerebral PNET. In conclusion, tandem HD melphalan is feasible and safe 
      in children, and achieved a high response rate in cerebral PNET. The observed 
      PK-PD relationships may help us design PK-guided outpatient treatment.
FAU - Vassal, G
AU  - Vassal G
AD  - Department of Paediatric Oncology, Institut Gustave-Roussy, Villejuif, France.
FAU - Tranchand, B
AU  - Tranchand B
FAU - Valteau-Couanet, D
AU  - Valteau-Couanet D
FAU - Mahe, C
AU  - Mahe C
FAU - Couanet, D
AU  - Couanet D
FAU - Schoeppfer, C
AU  - Schoeppfer C
FAU - Grill, J
AU  - Grill J
FAU - Kalifa, C
AU  - Kalifa C
FAU - Hill, C
AU  - Hill C
FAU - Ardiet, C
AU  - Ardiet C
FAU - Hartmann, O
AU  - Hartmann O
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PL  - England
TA  - Bone Marrow Transplant
JT  - Bone marrow transplantation
JID - 8702459
RN  - 0 (Antineoplastic Agents, Alkylating)
RN  - Q41OR9510P (Melphalan)
SB  - IM
MH  - Adolescent
MH  - Antineoplastic Agents, Alkylating/*administration & dosage/pharmacology/toxicity
MH  - Area Under Curve
MH  - Cerebellar Neoplasms/*therapy
MH  - Child
MH  - Child, Preschool
MH  - Dose-Response Relationship, Drug
MH  - Drug Administration Schedule
MH  - Female
MH  - Hematopoietic Stem Cell Transplantation/*methods/standards
MH  - Humans
MH  - Infant
MH  - Male
MH  - Medulloblastoma/*therapy
MH  - Melphalan/*administration & dosage/*pharmacology/toxicity
MH  - Metabolic Clearance Rate
MH  - Neuroblastoma/*therapy
MH  - *Transplantation Conditioning/methods/standards
EDAT- 2001/04/21 10:00
MHDA- 2001/08/31 10:01
CRDT- 2001/04/21 10:00
PHST- 2000/08/03 00:00 [received]
PHST- 2000/11/14 00:00 [accepted]
PHST- 2001/04/21 10:00 [pubmed]
PHST- 2001/08/31 10:01 [medline]
PHST- 2001/04/21 10:00 [entrez]
AID - 10.1038/sj.bmt.1702806 [doi]
PST - ppublish
SO  - Bone Marrow Transplant. 2001 Mar;27(5):471-7. doi: 10.1038/sj.bmt.1702806.