High Dose Chemotherapy with Autologous Stem Cell Transplantation in Hepatoblastoma does not Improve Outcome. Results of the GPOH Study HB99

Abstract

Introduction The purpose of the German HB99 trial (1999–2008) for hepatoblastoma (HB), was primarily to analyse the effect of high dose (HD) chemotherapy with carboplatin/etoposide (CE) in high risk (HR) patients with extended tumors, vessel involvement, extrahepatic tumor or distant metastases. In standard risk (SR) patients the effect of treatment reduction was analysed.

Methods HR patients received 2 cycles CE at conventional dose, followed by 2 at HD with subsequent autologous stem cell transplantation before delayed surgery. SR patients received 3–4 cycles of ifosfamide, cisplatin and doxorubicin (IPA) and delayed surgery. Analysis was on an intention to treat basis including resection rate, AFP decline, event free survival (EFS) and overall survival (OS). The patients with HD therapy were additionally analysed on an “as treated” basis. The results were compared to historical/published data.

Results Of the 142 patients, the 5-y OS was 58% for the 57 HR patients and 94% for the 85 SR patients. The AFP decline after 2 cycles CE was ≥ 50% in > 90% of the patients. 12/18 (67%) patients treated with HD therapy showed an AFP decline after the first cycle (as treated). Tumor resection was possible in 89% of the patients. The median FU was 7.4 years. Late deaths occurred in 4 patients.

Conclusion Use of HD chemotherapy for HB did not improve patient outcomes, compared to contemporaneous and more recent trials (SIOPEL 4 trial). Reduction of therapy in SR patients was possible without worsening of results compared to previous trials. The tumor response to CE was good. CE can therefore be considered for relapse patients.

Zusammenfassung

Hintergrund Die deutsche Studie HB99 für Hepatoblastome (HB) hatte das primäre Ziel den Effekt der Hochdosis (HD) Chemotherapie mit Carboplatin/Etoposid (CE) bei Hochrisiko (HR) Patienten mit ausgedehnten Tumoren, Gefäßbeteiligung, extrahepatischem Tumor oder Fernmetastasen zu analysieren. Zusätzlich wurde eine Therapiereduktion bei Standardrisiko (SR) Patienten analysiert.

Methoden HR Patienten erhielten 2 Blöcke CE in konventioneller Dosis gefolgt von 2 mit HD mit anschließender Stammzelltransplantation und Resektion. SR Patienten erhielten 3–4 Blöcke Ifosfamid, Cisplatin und Doxorubicin (IPA) mit verzögerter Resektion. Die Analyse nach „intention to treat“ beinhaltete Resektionsrate, AFP Abfall, ereignisfreies Überleben (EFS) und Gesamtüberleben (OS). Die mit HD Therapie behandelten Patienten wurden zusätzlich nach „as treated“ ausgewertet. Die Ergebnisse wurden mit historischen/publizierten Daten verglichen.

Ergebnisse Von 142 Patienten war das 5-J OS der 57 HR Patienten 58% das 5-J OS der 85 SR Patienten 94%. Ein AFP Abfall ≥ 50% war nach 2 Blöcken CE bei > 90% der Patienten erreicht worden. 12/18 (67%) der mit HD behandelten Patienten zeigten eine AFP Abfall nach dem ersten Block (as treated). Eine Tumorresektion konnte in 89% der Patienten durchgeführt werden. Die mittlere Nachbeobachtung war 7,4 Jahre. Späte Todesfälle traten bei 4 Patienten auf.

Schlussfolgerung Mit der HD Chemotherapie konnte das Gesamtüberleben der Patienten mit HB nicht verbessert werden, verglichen mit zeitgleichen oder neueren Studien (SIOPEL 4). Die Therapie für SR Patienten konnte reduziert werden ohne die guten Ergebnisse früherer Studien zu verändern. Das Ansprechen des Tumors auf CE war gut, daher kann CE für Rezidivpatienten erwogen werden.

Key words

hepatoblastoma - high dose chemotherapy - childhood liver tumor - trial HB99

Schlüsselwörter

Hepatoblastom - Hochdosischemotherapie - kindlicher Lebertumor - Lebertumorstudie HB99

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