Short topotecan-based induction regimen in newly diagnosed high-risk neuroblastoma.
OBJECTIVE
Topotecan is an active drug in relapsed neuroblastoma. We investigated the efficacy and toxicity of a topotecan-based induction regimen in newly diagnosed neuroblastoma.


METHODS
Patients older than 1 year with either metastatic or localised stage 2-3 MYCN-amplified neuroblastoma received 2 courses of high-dose topotecan (HD-TPT) 6mg/m(2) and high-dose cyclophosphamide (HD-CPM) 140 mg/kg, followed by 2 courses of ifosfamide, carboplatin and etoposide (ICE) every 28 days. After surgery on primary tumour, a fifth course with vincristine, doxorubicin and CPM was given, followed by high-dose chemotherapy with stem cell support. Response was assessed in accordance with the International Neuroblastoma Response Criteria.


RESULTS
Of 35 consecutive patients, 33 had metastatic disease. The median length of induction phase was 133 days (range 91-207) and time to high-dose chemotherapy was 208 days (range 156-285). The median tumour volume reduction was 55% after two HD-TPT/HD-CPM courses and 80% after four courses. Radical surgery was performed in 16/27 patients after chemotherapy. After the fifth course, 29/34 patients (85%) had achieved a partial remission (12) or a CR/very good partial remission (17). CR of metastases was achieved in 13/32 (41%) and bone marrow was in complete remission in 16/24 patients (67%). Grade 4 neutropenia and/or thrombocytopenia occurred in 100% of HD-TPT/HD-CPM and in 95% of ICE courses, while non-haematological toxicities were manageable.


CONCLUSIONS
These data indicate that our induction regimen is feasible and well tolerated. A major response rate of 85% with 41% complete metastatic response confirms this regimen as effective induction in high-risk neuroblastoma.
Department of Paediatric Oncology-Hematology, Ospedale Pediatrico Bambino Gesù IRCCS, Rome, Italy. deioris@opbg.net
Maria Antonietta
MA
De Ioris
Aurora
A
Castellano
Ilaria
I
Ilari
Maria Carmen
MC
Garganese
Gianluigi
G
Natali
Alessandro
A
Inserra
Rita
R
De Vito
Lucilla
L
Ravà
Maria Debora
MD
De Pasquale
Franco
F
Locatelli
Alberto
A
Donfrancesco
Alessandro
A
Jenkner
D000008:Abdominal Neoplasms / Q000188:drug therapy*; D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects; D007223:Infant; D053208:Kaplan-Meier Estimate; D008130:Lomustine / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008558:Melphalan / Q000008:administration & dosage / Q000009:adverse effects; D015080:Mesna / Q000008:administration & dosage / Q000009:adverse effects; D009447:Neuroblastoma / Q000188:drug therapy* / Q000556:secondary; D010865:Pilot Projects; D012307:Risk Factors; D013899:Thoracic Neoplasms / Q000188:drug therapy*; D019772:Topotecan / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
D005047:Etoposide; D008130:Lomustine; D019772:Topotecan; D016190:Carboplatin; D015080:Mesna; D008558:Melphalan; D007069:Ifosfamide