Response to paclitaxel, topotecan, and topotecan-cyclophosphamide in children with untreated disseminated neuroblastoma treated in an upfront phase II investigational window: a pediatric oncology group study.
OBJECTIVE
Most children older than 1 year of age with metastatic neuroblastoma (NB) die despite intensive chemotherapy and bone marrow transplantation. The Pediatric Oncology Group conducted a study of paclitaxel, topotecan, and topotecan-cyclophosphamide (topo-cyclo) in newly diagnosed children with stage IV NB.


METHODS
There were 102 patients enrolled between September 1993 and October 1995; two of them were later shown to be ineligible. Of the remaining 100 patients, the first cohort of 33 patients received paclitaxel 350 mg/m(2) intravenously (IV) over 24 hours every 14 to 21 days; the next 33 patients received topotecan 2 mg/m(2)/d for 5 days IV every 21 days; a third cohort of 34 patients were treated with IV cyclophosphamide 250 mg/m(2) followed by topotecan 0.75 mg/m(2) each day for 5 days every 21 days. Patients were re-evaluated after two courses and then treated with intensive induction therapy and bone marrow transplantation.


RESULTS
Objective responses (complete response + partial response + mixed response) were documented in 67% of children who received topotecan, 76% after topo-cyclo, and 25% after paclitaxel. Four patients had grade 3 to 4 allergic reactions to paclitaxel; most patients developed grade 3 to 4 marrow suppression after topotecan or topo-cyclo. Neither disease-free survival nor overall survival differed significantly between children who received a phase II agent and those who did not. The 6-year disease-free survival and overall survival rates for all 100 children were 18% +/- 5% and 26% +/- 5%, respectively.


CONCLUSIONS
Topotecan and topo-cyclo are active in children with NB, are well tolerated, and should be evaluated further in combination regimens.
Kretschmar
Cynthia S
CS
Boston Floating Hospital for Infants and Children, Department of Pediatrics, Division of Pediatric Oncology, 750 Washington St, Box 14, Boston, MA 02111, USA. ckretschmar@tufts-nemc.org
Kletzel
Morris
M
Murray
Kevin
K
Thorner
Paul
P
Joshi
Vijay
V
Marcus
Robert
R
Smith
E Ide
EI
London
Wendy B
WB
Castleberry
Robert
R
D000293:Adolescent; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009447:Neuroblastoma / Q000188:drug therapy*; D017239:Paclitaxel / Q000009:adverse effects / Q000627:therapeutic use*; D015996:Survival Rate; D019772:Topotecan / Q000009:adverse effects / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D019772:Topotecan; D003520:Cyclophosphamide; D017239:Paclitaxel