Although the prognosis of childhood
cancers has dramatically improved over the last three decades, new active drugs are needed. Camptothecins represent a very attractive new class of anticancer drugs to develop in paediatric oncology. The preclinical and clinical development of two of these
DNA-topoisomerase I inhibitors, i.e.
topotecan and
irinotecan, is ongoing in paediatric
malignancies. Here we review the currently available results of this evaluation.
Topotecan proved to be active against several paediatric tumour xenografts. In paediatric phase I studies exploring several administration schedules, myelosuppression was dose-limiting. The preliminary results of
topotecan evaluation in phase II study showed antitumour activity in
neuroblastoma (response rate: 15% at relapse and 37% in newly diagnosed patients with disseminated disease) and in metastatic
rhabdomyosarcoma (40% in untreated patients).
Topotecan-containing
drug combinations are currently investigated.
Irinotecan displayed a broad spectrum of activity in paediatric solid tumour xenografts, including rhabdo-
myosarcoma,
neuroblastoma, peripheral primitive neuroectodermal tumour,
medulloblastoma,
ependymoma,
malignant glioma and juvenile
colon cancer. For several of these histology types, tumour-free survivors have been observed among animals bearing an advanced-stage tumour at time of treatment. The clinical evaluation of
irinotecan in children is ongoing.
Irinotecan undergoes a complex in vivo biotransformation involving several
enzyme systems, such as
carboxylesterase, UDPGT and
cytochrome P450, in children as well as in adults. Preclinical studies of both drugs have shown that their activity was schedule-dependent. The optimal schedule of administration is an issue that needs to be addressed in children. In conclusion, the preliminary results of the paediatric evaluation of
camptothecin derivatives show very encouraging results in childhood
malignancies. The potential place of camptothecins in the treatment of paediatric malignant tumours is discussed.