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Titolo:
PRECLINICAL DEVELOPMENT OF CAMPTOTHECIN DERIVATIVES AND CLINICAL-TRIALS IN PEDIATRIC ONCOLOGY
Autore:
VASSAL G; PONDARRE C; BOLAND I; CAPPELLI C; SANTOS A; THOMAS C; LUCCHI E; IMADALOU K; PEIN F; MORIZET J; GOUYETTE A;
Indirizzi:
INST GUSTAVE ROUSSY,LAB PHARMACOTOXICOL & PHARMACOGENET,CNRS,URA 147,RUE CAMILLE DESMOULINS F-94805 VILLEJUIF FRANCE INST GUSTAVE ROUSSY,DEPT PEDIAT ONCOL F-94805 VILLEJUIF FRANCE
Titolo Testata:
Biochimie
fascicolo: 3, volume: 80, anno: 1998,
pagine: 271 - 280
SICI:
0300-9084(1998)80:3<271:PDOCDA>2.0.ZU;2-I
Fonte:
ISI
Lingua:
ENG
Soggetto:
DNA-TOPOISOMERASE-I; CONTINUOUS-INFUSION TOPOTECAN; HUMAN TUMOR XENOGRAFTS; PHASE-I; ANTITUMOR-ACTIVITY; IRINOTECAN CPT-11; SOLID TUMORS; SYSTEMIC EXPOSURE; NONHUMAN-PRIMATES; CYTO-TOXICITY;
Keywords:
IRINOTECAN; TOPOTECAN; TOPOISOMERASE I; CHILDREN; XENOGRAFTS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
66
Recensione:
Indirizzi per estratti:
Citazione:
G. Vassal et al., "PRECLINICAL DEVELOPMENT OF CAMPTOTHECIN DERIVATIVES AND CLINICAL-TRIALS IN PEDIATRIC ONCOLOGY", Biochimie, 80(3), 1998, pp. 271-280

Abstract

Although the prognosis of childhood cancers ha; dramatically improvedover 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 1 inhibitors, ie 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 wasdose-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 disseminateddisease) and in metastatic rhabdomyosarcoma (40% in untreated patients). Topotecan-containing drug combinations are currently investigated. Irinotecan displayed a broad spectrum of activity in paediatric solidtumour xenografts, including rhabdomyosarcoma, 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 inadults. 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 camntothecins in the treatment of paediatric malignant tumours is discussed. ((C) Society francaise de biochimie et biologie moleculaire / Elsevier, Paris).

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/11/20 alle ore 04:31:45