Targeted Therapeutics in Treatment of Children and Young Adults with Solid Tumors: an Expert Survey and Review of the Literature

Abstract

Background:

Although prognosis of children with solid tumors is steadily improving, long-term survival is not achievable in all patients, especially in patients with recurrent or refractory disease. Despite the increasing number of targeted therapeutics (TT), only very few TT have been introduced into clinical protocols. Accordingly, clinical experience concerning the efficacy and safety of these drugs is limited. This may possibly discourage oncologists from administering TT to children.

Methods:

We performed a comprehensive review of the literature to identify TT that may be considered for treatment of children and young adults with solid tumors. Moreover, we interviewed an expert panel of the Society for Pediatric Oncology and Hematology (GPOH) using questionnaires in a modified Delphi process in order to describe the experts’ experiences in the use of these TT.

Results:

Among 30 TT identified to be possibly useful in children and young adults, imatinib, bevacizumab and rapamycin were most widely used. These drugs were reported as having mostly little to no severe adverse events and seem to induce at least partial responses in a subset of patients. In addition, our study confirms and expands the present knowledge about adverse events and the potential efficacy of 5 other commonly used TT in this population.

Conclusions:

This information may be useful for oncologists when administering these TT to children and young adults with solid tumors. Controlled clinical trials are urgently needed to test their safety and efficacy.

Zusammenfassung

Hintergrund:

Obwohl sich die Prognose für Kinder mit soliden Tumoren stetig verbessert, ist ein Langzeitüberleben nicht bei allen Patienten zu erzielen. Bei refraktärer oder rezidivierter Tumorerkrankung ist eine Heilung nur in Ausnahmefällen möglich. Trotz der wachsenden Zahl an sogenannten targeted therapeutics (TT) finden nur wenige davon routinemäßig klinische Verwendung. Daher ist die klinische Erfahrung mit diesen Medikamenten bezüglich ihrer Wirksamkeit und Verträglichkeit noch sehr begrenzt, was pädiatrische Onkologen möglicherweise davon abhält, sie bei Kindern einzusetzen.

Methoden:

Wir führten eine umfangreiche Literaturrecherche durch, um jene TT zu identifizieren, die für die Behandlung von Kindern und jungen Erwachsenen mit soliden Tumoren geeignet sein könnten. Zusätzlich befragten wir eine Gruppe von Experten der Gesellschaft für Pädiatrische Onkologie und Hämatologie (GPOH) im Rahmen einer modifizierten Delphi-Studie mithilfe von Fragebögen, um deren Erfahrungen mit diesen TT zu dokumentieren.

Ergebnisse:

Unter 30 TT, die für den Einsatz bei Kindern geeignet erschienen, waren Imatinib, Bevacizumab und Rapamycin diejenigen, die am häufigsten angewendet wurden. Deren Einsatz führte nur sehr selten zu schweren unerwünschten Wirkungen. Bei einem Teil der Patienten wurde über eine partielle Tumorregression berichtet. Darüber hinaus bestätigt und erweitert unsere Studie den derzeitigen Kenntnisstand über unerwünschte und erwünschte Wirkungen von 5 weiteren bei der Behandlung von Kindern mit soliden Tumoren häufig eingesetzten TT.

Schlussfolgerung:

Diese Informationen könnten für pädiatrische Onkologen bei der Verabreichung dieser TT an Kinder mit soliden Tumoren hilfreich sein. Die Wirksamkeit und Verträglichkeit dieser Medikamente muss rasch in kontrollierten klinischen Studien überprüft werden.

Key words

targeted therapeutics - solid tumor - children - Delphi survey - biologicals

Schlüsselwörter

zielgerichtete Arzneimittel - solider Tumor - Kinder - Delphi-Umfrage - biologische medizinische Produkte

^* These authors equally contributed to this work.

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