Topotecan, cyclophosphamide, and etoposide (TCE) in the treatment of high-risk neuroblastoma. Results of a phase-II trial.
OBJECTIVE
Relapsed high-risk neuroblastoma patients still have a poor prognosis. This phase-II trial assessed a new topotecan containing chemotherapy approach in patients with active disease.


METHODS
Chemotherapy consisted of topotecan (1.0 mg/m(2)/day 168-h continuous infusion), cyclophosphamide (100 mg/m(2)/day 1-h-infusion days 1-7 starting 6 h prior to topotecan), and etoposide (100 mg/m(2)/day 1-h-infusion days 8-10). Patients with relapsed neuroblastoma were scheduled for six cycles, untreated patients for two cycles followed by standard high-risk treatment.


RESULTS
Main toxicity observed during 153 cycles were grade 3-4 leukopenia (97% of cycles), thrombocytopenia (92%), neutropenic fever (52%), and mucositis (10%). No treatment related fatal toxicity occurred. Complete or partial response was achieved in 19 of 31 (61%) evaluable relapsed patients and 8 of 11 (72%) untreated patients.


CONCLUSIONS
The combination of topotecan, cyclophosphamide, and etoposide is tolerable and effective in relapsed and untreated neuroblastoma. Myelotoxicity is the main side effect but seems justified in view of the encouraging response rates. A randomized phase-III trial in primary disease has been commenced.
Simon
Thorsten
T
Children's Hospital, Department of Pediatric Oncology and Hematology, University of Cologne, Kerpener Strasse 62, 50924 Cologne, Germany. thorsten.simon@uk-koeln.de
Längler
Alfred
A
Harnischmacher
Urs
U
Frühwald
Michael C
MC
Jorch
Norbert
N
Claviez
Alexander
A
Berthold
Frank
F
Hero
Barbara
B
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D009447:Neuroblastoma / Q000188:drug therapy* / Q000401:mortality; D019772:Topotecan / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
D005047:Etoposide; D019772:Topotecan; D003520:Cyclophosphamide