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DOI: 10.1055/s-2005-836518
© Georg Thieme Verlag Stuttgart · New York
Infants with Stage 4 Neuroblastoma: The Impact of the Chimeric Anti-GD2-Antibody ch14.18 Consolidation Therapy
Säuglinge mit Neuroblastom Stadium 4: Konsolidierungsbehandlung mit chimärem anti-GD2-Antikörper ch14.18Publication History
Publication Date:
27 April 2005 (online)
Abstract
Background: Antibody treatment is considered tolerable and potentially effective in the therapy of neuroblastoma. We have analyzed the clinical data of infants < 1 year with stage 4 neuroblastoma with regard to the consolidation treatment. Patients and Methods: Infants < 1 year with stage 4 neuroblastoma who completed initial treatment (6-8 chemotherapy cycles followed either by 4 cycles low dose oral chemotherapy or high dose chemotherapy with stem cell transplantation) without event were eligible for this trial. Consolidation therapy consisted of 6 cycles of antibody ch14.18 (20 mg/m² × d ch14.18 for 5 days every 2 months) or 12 months oral maintenance chemotherapy (MT). Results: Of 59 evaluable patients, 31 received a total of 159 ch14.18 cycles, 16 received MT instead, and 12 had no further treatment. Fever (47 % of cycles), abnormal CRP without infection (25 %), rash (23 %), cough (16 %), and pain (8 %) were the main side effects. Univariate analysis found no difference in event free survival (3-year-EFS 80.5 ± 7.1 %, 87.5 ± 8.3 %, and 75.0 ± 12.5 % for patients treated with antibody ch14.18, MT, and no further therapy, p = 0.433) and overall survival (3-year-OS 90.1 ± 5.4 %, 93.8 ± 6.0 %, and 91.7 ± 8.0 % for patients treated with antibody ch14.18, MT, and no further therapy, p = 0.931). Multivariate analysis failed to demonstrate an advantage of antibody treatment. Conclusion: The outcome of infants with stage 4 neuroblastoma is good. Consolidation treatment with ch14.18 was tolerable but associated with fever, elevated CRP, rash, cough, and pain as side effects. Compared to oral maintenance chemotherapy and no consolidation treatment, ch14.18 treatment had no impact on the patients' outcome which confirms the results found in children > 1 year.
Zusammenfassung
Hintergrund: Die Therapie mit chimärem anti-GD2-Antikörper ch14.18 ist möglicherweise eine tolerable und wirkungsvolle Ergänzung der Behandlung des metastasierten Neuroblastoms. Wir haben deshalb die klinischen Daten von Säuglingen mit Neuroblastom Stadium 4 unter Berücksichtigung der Konsolidierungsbehandlung analysiert. Patienten und Methode: Alle Säuglinge < 1 Jahr mit Neuroblastom Stadium 4, welche die initiale Behandlung (6-8 Blöcke Chemotherapie gefolgt von einer oralen Erhaltungschemotherapie oder Megatherapie mit Stammzelltransplantation) vollständig erhalten hatten, wurden in die Analyse eingeschlossen. Zur Konsolidierung erhielten die Patienten entweder Antikörper ch14.18 (20 mg/m² × d an 5 Tagen im Abstand von 2 Monaten) oder eine 12-monatige orale Dauertherapie (DT). Ergebnisse: 59 Patienten wurden eingeschlossen. 31 von ihnen erhielten 159 Antikörperzyklen, 16 Patienten eine DT, weitere 12 erhielten keine Konsolidierung. Wesentliche Nebenwirkungen der Antikörperbehandlung waren: Fieber (47 % aller ch14.18-Zyklen), CRP-Erhöhung ohne Infektion (25 %), Ausschlag (23 %), Husten (16 %) und Schmerzen (8 %). In der univariaten Analyse fand sich kein Unterschied zwischen den Gruppen hinsichtlich des ereignisfreien Überlebens (3-Jahres-EFS 80,5 ± 7,1 % nach Antikörpertherapie, 87,5 ± 8,3 % nach ET und 75,0 ± 12,5 % ohne Konsolidierung, p = 0,433) und des Gesamtüberlebens (3-Jahres-OS 90,1 ± 5,4 % nach ch14.18, 93,8 ± 6,0 % nach ET und 91,7 ± 8,0 % ohne Konsolidierung, p = 0,931). Auch in der multivariaten Analyse konnte kein Vorteil für die Behandlung mit ch14.18 gezeigt werden. Schlussfolgerung: Säuglinge mit Neuroblastom Stadium 4 haben eine exzellente Prognose. Eine Konsolidierung mit anti-GD2-Antikörper ch14.18 ist tolerabel. Wesentliche Nebenwirkungen waren Fieber, CRP-Erhöhung, Ausschlag, Husten und Schmerzen. Verglichen mit einer oralen Erhaltungstherapie oder keiner anschließenden Konsolidierung fand sich kein eindeutiger Vorteil der Antikörpertherapie. Das bestätigte die bei Kindern > 1 Jahr gewonnen Erfahrungen.
Key words
clinical trial - neuroblastoma - immunotherapy - anti-GD2 monoclonal antibody - ch14.18 - side effects - infants
Schlüsselwörter
klinische Studie - Neuroblastom - Immuntherapie - anti-GD2-Antikörper - ch14.18 - Nebenwirkungen - Säuglinge
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Thorsten SimonM. D.
Children's Hospital · Department of Pediatric Oncology and Hematology · University of Cologne
Kerpener Strasse 62
50924 Köln
Germany
Phone: +49/2 21/4 78 43 80
Fax: +49/2 21/4 78 68 01
Email: thorsten.simon@uk-koeln.de