A phase II trial of rebeccamycin analogue (NSC #655649) in children with solid tumors: a Children's Oncology Group study.

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. PROCEDURE: 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. (c) 2007 Wiley-Liss, Inc.