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Klin Padiatr 2012; 224(06): 366-371
DOI: 10.1055/s-0032-1327579
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Systemic Treatment of Adrenocortical Carcinoma in Children: Data from the German GPOH-MET 97 Trial

Systemische Therapie von Nebennierenrindenkarzinomen im Kindesalter: Ergebnisse des GPOH-MET-97-Protokolls
A. Redlich
1   Pediatric Oncology, Otto-von-Guericke-University, Magdeburg, Germany
,
N. Boxberger
1   Pediatric Oncology, Otto-von-Guericke-University, Magdeburg, Germany
,
D. Strugala
1   Pediatric Oncology, Otto-von-Guericke-University, Magdeburg, Germany
,
M. C. Frühwald
2   Pediatric Oncology, University Childrens Hospital Münster, Münster, ­Germany
,
I. Leuschner
3   Institut für Pathologie der Universität Kiel, Kiel, Germany
,
S. Kropf
4   Institute of Biometry and Medical Informatics, Otto-von-Guericke-­University, Magdeburg, Germany
,
P. Bucsky
5   Pediatric Oncology, University of Lübeck, Lübeck, Germany
,
P. Vorwerk
1   Pediatric Oncology, Otto-von-Guericke-University, Magdeburg, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
09 November 2012 (online)

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Abstract

Background:

Adrenocortical cancer (ACC) in childhood is a rare disease with poor prognosis. Complete surgical resection, systemic chemotherapy, and mitotane therapy are important curative treatment options for patients with advanced-stage tumors. Since 1997, pediatric ACC patients in Germany have been treated according to the non-randomized, single arm study GPOH-MET-97.

Patients and methods:

Data regarding disease course, treatment, and survival rates of 60 patients (age 0.24–17.8 years) with ACC treated according to the GPOH-MET-97 protocol were collected and analyzed to determine outcome, with a focus on examining the effectiveness of mitotane therapy.

Results:

Among all patients, event-free survival and overall survival were found to be 43.3% and 64.8%, respectively. Chemotherapy with VCR, IFO, ADR, CARBO, and VP16 had been provided to 34 patients (56.6%) in different settings (neoadjuvant, adjuvant, and salvage) and mitotane therapy to 32 patients (53.3%). Duration of mitotane treatment longer than 6 months and mitotane levels greater than 14 mg/l were found to be associated with significantly better survival. Local relapse was found to be associated with a worse prognosis compared to distant metastasis only.

Conclusions:

Systemic chemotherapy and mitotane therapy are important therapeutic options in the treatment of advanced pediatric ACC patients. Neoadjuvant therapy should be considered for patients with primarily incomplete resectable or inoperable tumors, and tumor spillage is an indication for adjuvant chemo- and mitotane therapy. All pediatric ACC patients should be treated in pediatric oncological centers according to a consistent protocol in a highly interdisciplinary setting.

Zusammenfassung

Hintergrund:

Nebennierenrindenkarzinome (ACC) sind bei Kindern seltene Tumoren, die eine hohe Letalität besitzen. Neben der kompletten chirurgischen Resektion des Tumors sind die systemische Chemo- und Mitotanetherapie wichtige Optionen für einen kurativen Ansatz. Seit 1997 werden Kinder mit ACC in Deutschland nach der einarmigen, nicht-randomisierten GPOH-MET-97 Studie behandelt.

Patienten und Methoden:

60 Patienten mit ACC im Alter zwischen 2 Monaten und 18 Jahren wurden nach dem GPOH-MET-97-Protokoll behandelt. Erkrankungsverlauf, Therapie und Ergebnisse wurden unter besonderer Berücksichtigung der Mitotanetherapie analysiert.

Ergebnisse:

Das ereignisfreie Überleben von allen Patienten betrug 43.3%, das Gesamtüberleben 64.8%. Die Chemotherapie bestehend aus VCR, IFO, ADR, CARBO und VP16 erhielten 34 Patienten (56.6%) in unterschiedlichen Settings (neoadjuvant, adjuvent, salvage). Mit Mitotane wurden insgesamt 32 Patienten behandelt (53.3%). Mitotanebehandlung länger als 6 Monate und Mitotanespiegel >14 mg/l waren mit einem signifikant besseren Überleben assoziiert. Patienten mit lokalem Rezidiv hatten eine schlechtere Prognose als Patienten mit Fernmetastasen.

Schlussfolgerung:

Die Behandlung von Patienten mit ACC mit Chemotherapie und Mitotane ist eine wichtige Option bei Kindern mit fortgeschrittenem ACC. Eine neo­adjuvente Therapie sollte bei Patienten mit primär inkomplett rese­zierbar oder inoperablen Tumoren in Be­tracht gezogen werden. Tumor Spillage ist eine Indi­kation für systemische Chemo- und Mito­tanetherapie. Alle Kinder mit ACC sollten in ­pädiatrisch-onkologischen Zentren in enger interdisziplinärer Zusammenarbeit nach einheitlichen Therapieprotokollen betreut werden.

Key words

adrenocortical carcinoma - GPOH-MET-97 protocol - mitotane - neoadjuvant therapy - pediatric oncology

Schlüsselwörter

Nebennierenrindenkarzinom - GPOH-MET-97 Protokoll - Mitotane - neoadjuvante Chemo­therapie - Kinderonkologie
 

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