title: A phase II trial of rebeccamycin analogue (NSC #655649) in children with solid tumors: a Children's Oncology Group study.
abstract: BACKGROUND
  Rebeccamycin Analogue (NSC #655649), a chemically synthesized glycosyl-dichloro-indolocarbazole derivative of rebeccamycin with topoisomerase inhibiting activity, has in vitro activity against pediatric tumor cell lines and tumor specimens including rhabdomyosarcoma, neuroblastoma, Ewing's sarcoma and medulloblastoma.
  
  
  METHODS
  The primary objective of this trial was to determine the response rate to Rebeccamycin analogue NSC #655649 in children with refractory solid and CNS tumors. Secondary objectives included further evaluation of the toxicity and pharmacokinetic profile of Rebeccamycin analogue in children with relapsed and refractory cancer. A two-stage design was used for this Phase II trial. Rebeccamycin analogue, 650 mg/m(2), was administered every 21 days, and could be escalated to 780 mg/m(2) in subsequent cycles to achieve a maximum plasma drug concentration >5 microg/ml.
  
  
  RESULTS
  From July 2000 to October 2004, 72 male and 61 female eligible patients were enrolled. Of 126 evaluable patients for response, only 4 patients had an objective response: 3 patients with rhabdomyosarcoma (1 CR and 2 PR) and 1 patient with neuroblastoma (1 PR). Grade 3 or 4 myelosuppression occurred in 81% (215/265) of patient courses and hepatotoxicity in 14% (37/265) of patient courses. Transient pancreatitis and/or elevation of amylase and lipase occurred in 6 patients.
  
  
  CONCLUSIONS
  The 15% response rate to Rebeccamycin analogue observed in patients with rhabdomyosarcoma, while of interest, is associated with significant myelosuppression. With a global response rate of 3% observed in children with relapsed CNS and non-CNS solid tumors, further development of Rebeccamycin analogue in pediatric solid tumors is not recommended.
authors.affiliation: University of Texas Health Science Center, San Antonio, Texas, USA. Langevin@UTHSCSA.edu
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Langevin
authors.forename: Mark
authors.initials: M
authors.lastname: Bernstein
authors.forename: John G
authors.initials: JG
authors.lastname: Kuhn
authors.forename: Susan M
authors.initials: SM
authors.lastname: Blaney
authors.forename: Percy
authors.initials: P
authors.lastname: Ivy
authors.forename: Junfeng
authors.initials: J
authors.lastname: Sun
authors.forename: Zhengjia
authors.initials: Z
authors.lastname: Chen
authors.forename: Peter C
authors.initials: PC
authors.lastname: Adamson
mesh_terms: D000293:Adolescent; D000328:Adult; D000617:Aminoglycosides / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001855:Bone Marrow Diseases / Q000139:chemically induced; D002227:Carbazoles; D016543:Central Nervous System Neoplasms / Q000188:drug therapy; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology; D002648:Child; D002675:Child, Preschool; D005260:Female; D005960:Glucosides; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007262:Infusions, Intravenous; D008297:Male; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors; D009369:Neoplasms / Q000188:drug therapy*; D010195:Pancreatitis / Q000139:chemically induced; D012208:Rhabdomyosarcoma / Q000188:drug therapy; D016879:Salvage Therapy; D059005:Topoisomerase II Inhibitors
chemical_list: D000617:Aminoglycosides; D000903:Antibiotics, Antineoplastic; D002227:Carbazoles; D005960:Glucosides; D009363:Neoplasm Proteins; D059005:Topoisomerase II Inhibitors; C093269:becatecarin