Topotecan by 21-day continuous infusion in children with relapsed or refractory solid tumors: a Children's Oncology Group study.
OBJECTIVE
The Children's Oncology Group conducted a phase II trial of 21-day continuous infusion topotecan to determine the response rate in pediatric patients with recurrent or refractory malignant solid tumors.


METHODS
Patients with Ewing sarcoma family of tumors (ESFT), osteosarcoma (OS), soft tissue sarcomas (STS), medulloblastoma (MB)/primitive neuroectodermal tumor (PNET), astrocytoma, or neuroblastoma (NB) recurrent or refractory to conventional therapy, measurable disease, and adequate organ function were treated with topotecan 0.3 mg/m2/day by continuous intravenous infusion for 21 consecutive days, followed by 7 days without therapy prior to response assessment.


RESULTS
Fifty-five patients were enrolled; two were ineligible, two were removed from protocol therapy prior to evaluation for response, and one was inevaluable for response, leaving 53 and 50 patients evaluable for toxicity and response, respectively. Objective responses were seen in 2/20 patients with ESFT (both partial responses, 4 and 19 courses), 0/10 OS patients, and 0/12 STS patients. There were insufficient patients enrolled to determine the response rate for the MB/PNET, astrocytoma, and NB strata. The most common Grade 3 or 4 toxicities during the first course of therapy were thrombocytopenia (12/53), neutropenia (8/53), and fatigue (7/53).


CONCLUSIONS
Intravenous topotecan by 21-day continuous infusion is tolerable in pediatric patients with recurrent or refractory solid tumors. Limited activity was seen in ESFT and further development of this topotecan schedule as a single agent is not warranted.
Hawkins
Douglas S
DS
Children's Hospital and Regional Medical Center, Seattle, WA, USA. Douglas.Hawkins@seattlechildrens.org
Bradfield
Scott
S
Whitlock
James A
JA
Krailo
Mark
M
Franklin
Janet
J
Blaney
Susan M
SM
Adamson
Peter C
PC
Reaman
Gregory
G
D000293:Adolescent; D000328:Adult; D001254:Astrocytoma / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D020714:Maximum Tolerated Dose; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D009447:Neuroblastoma / Q000188:drug therapy*; D018242:Neuroectodermal Tumors, Primitive / Q000188:drug therapy*; D009503:Neutropenia / Q000139:chemically induced; D012008:Recurrence; D012509:Sarcoma / Q000188:drug therapy*; D015996:Survival Rate; D013921:Thrombocytopenia / Q000139:chemically induced; D013997:Time Factors; D019772:Topotecan / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
D019772:Topotecan