title: Two-stage phase II study of imatinib mesylate in subjects with refractory or relapsing neuroblastoma.
abstract: BACKGROUND
  Cure rate for subjects with refractory or relapsing metastatic neuroblastoma is <5%. In the search for a novel therapy, continuous daily oral administration of imatinib mesylate was evaluated.
  
  
  METHODS
  Twenty-four subjects were enrolled in a two-stage study. Imatinib was administered for the first 4 weeks (cycle) at 170 mg/sqm b.i.d. If no major toxicity occurred, the dose was escalated to 300 mg/sqm b.i.d. for a maximum of 12 cycles. Clinical response and toxicity were evaluated according to international criteria. Pharmacokinetics (PK) profiles and tyrosine hydroxylase (TH) mRNA expression were also determined in a subset of subjects.
  
  
  RESULTS
  Five (21%) complete responses, with one subject still alive at 68 months, and 2 (8%) partial responses lasting up to 29 months were obtained. No grade 4 toxicity was observed. At steady-state, PK exposure (69.7 µg h/ml) was similar to that of adults receiving 1000 mg/die. Responses appear to correlate with the absence or presence of metastasis in the bone marrow (BM) alone, with low TH expression levels at study entry and low imatinib exposure.
  
  
  CONCLUSIONS
  Imatinib mesylate was well-tolerated and effective in the subset of subjects with low BM infiltration as only site of metastasis. Study identifier EudraCT: 2005-005778-63.
authors: Department of Hematology-Oncology, Istituto Giannina Gaslini, Genoa.
authors: L
authors: L
authors: Calafiore
authors: L
authors: L
authors: Amoroso
authors: O
authors: O
authors: Della Casa Alberighi
authors: R
authors: R
authors: Luksch
authors: G
authors: G
authors: Zanazzo
authors: A
authors: A
authors: Castellano
authors: M
authors: M
authors: Podda
authors: C
authors: C
authors: Dominici
authors: R
authors: R
authors: Haupt
authors: M V
authors: MV
authors: Corrias
authors: A
authors: A
authors: Garaventa
mesh_terms: D000293:Adolescent; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001549:Benzamides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019046:Bone Marrow Neoplasms / Q000556:secondary*; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D008137:Longitudinal Studies; D008297:Male; D009364:Neoplasm Recurrence, Local; D009447:Neuroblastoma / Q000188:drug therapy* / Q000556:secondary; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D012333:RNA, Messenger; D000068877:Imatinib Mesylate; D014446:Tyrosine 3-Monooxygenase