Topotecan-Vincristine-Doxorubicin in Stage 4 High-Risk Neuroblastoma Patients Failing to Achieve a Complete Metastatic Response to Rapid COJEC: A SIOPEN Study.
OBJECTIVE
Metastatic response to induction therapy for high-risk neuroblastoma is a prognostic factor. In the International Society of Paediatric Oncology Europe Neuroblastoma (SIOPEN) HR-NBL-1 protocol, only patients with metastatic complete response (CR) or partial response (PR) with ≤ three abnormal skeletal areas on iodine 123-metaiodobenzylguanidine ([123I]mIBG) scintigraphy and no bone marrow disease proceed to high dose therapy (HDT). In this study, topotecan-vincristine-doxorubicin (TVD) was evaluated in patients failing to achieve these criteria, with the aim of improving the metastatic response rate.


METHODS
Patients with metastatic high-risk neuroblastoma who had not achieved the SIOPEN criteria for HDT after induction received two courses of topotecan 1.5 mg/m2/day for 5 days, followed by a 48-hour infusion of vincristine, 2 mg/m2, and doxorubicin, 45 mg/m2.


RESULTS
Sixty-three patients were eligible and evaluable. Following two courses of TVD, four (6.4%) patients had an overall CR, while 28 (44.4%) had a PR with a combined response rate of 50.8% (95% confidence interval [CI], 37.9 to 63.6). Of these, 23 patients achieved a metastatic CR or a PR with ≤ 3 mIBG skeletal areas and no bone marrow disease (36.5%; 95% CI, 24.7 to 49.6) and were eligible to receive HDT. Toxicity was mostly haematological, affecting 106 of the 126 courses (84.1%; 95% CI, 76.5 to 90.0), and dose reduction was necessary in six patients. Stomatitis was the second most common nonhematological toxicity, occurring in 20 patients (31.7%).


CONCLUSIONS
TVD was effective in improving the response rate of high-risk neuroblastoma patients after induction with COJEC enabling them to proceed to HDT. However, the long-term benefits of TVD needs to be determined in randomized clinical trials.
Paediatric Oncology, Istituto Giannina Gaslini, Genova, Italy.
Loredana
L
Amoroso
Epidemiology and Biostatistics Unit, Istituto Giannina Gaslini, Genova, Italy.
Giovanni
G
Erminio
Institute of Cancer Sciences, Manchester Cancer Research Centre, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK.
Guy
G
Makin
Divisions of Cancer Therapeutics and Clinical Studies, Institute of Cancer Research and Children and Young People's Unit, The Royal Marsden NHS Foundation Trust, London, UK.
Andrew D J
ADJ
Pearson
Paediatric Oncology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
Penelope
P
Brock
Paediatric Oncology, Institute Gustave Roussy, Villejuif, France.
Dominique
D
Valteau-Couanet
Paediatric Oncology, Hospital Universitario La Fe, Valencia, Spain.
Victoria
V
Castel
Department of Hematology-Oncology Hopital des Enfants, Toulouse, France.
Marlène
M
Pasquet
Department of Paediatric Hematology, Oncology and Stem Cell Transplantation, Ghent University Hospital, Ghent, Belgium.
Genevieve
G
Laureys
Pediatric Intensive Care and Onco-Hematology Units, Nantes Hospital, Nantes, France.
Caroline
C
Thomas
Department of Paediatric Oncology, Istituto Nazionale Tumori, Milan, Italy.
Roberto
R
Luksch
Children's Cancer Research Institute, St. Anna Children's Hospital, Vienna, Austria.
Ruth
R
Ladenstein
Epidemiology and Biostatistics Unit, Istituto Giannina Gaslini, Genova, Italy.
Riccardo
R
Haupt
Paediatric Oncology, Istituto Giannina Gaslini, Genova, Italy.
Alberto
A
Garaventa
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000188:drug therapy* / Q000473:pathology; D012307:Risk Factors; D059004:Topoisomerase I Inhibitors / Q000008:administration & dosage; D019772:Topotecan / Q000008:administration & dosage; D014750:Vincristine / Q000008:administration & dosage
D059004:Topoisomerase I Inhibitors; D014750:Vincristine; D019772:Topotecan; D004317:Doxorubicin
Child; Neoplasm; Neuroblastoma; Phase 2 clinical trial; Recurrence; Second line drugs