Results of a phase II upfront window of pharmacokinetically guided topotecan in high-risk medulloblastoma and supratentorial primitive neuroectodermal tumor

Clinton F. Stewart, Lisa C. Iacono, Murali Chintagumpala, Stewart J. Kellie, David Ashley, W. C. Zamboni, M. N. Kirstein, Maryam Fouladi, Louis G. Seele, Dana Wallace, Peter J. Houghton, Amar Gajjar

Producción científica: Articlerevisión exhaustiva

60 Citas (Scopus)

Resumen

Purpose: To assess the antitumor efficacy of pharmacokinetically guided topotecan dosing in previously untreated patients with medulloblastoma and supratentorial primitive neuroectodermal tumors, and to evaluate plasma and CSF disposition of topotecan in these patients. Patients and Methods: After maximal surgical resection, 44 children with previously untreated high-risk medulloblastoma were enrolled, of which 36 were assessable for response. The topotecan window consisted of two cycles, administered initially as a 30-minute infusion daily for 5 days, lasting 6 weeks. Pharmacokinetic studies were conducted on day 1 to attain a topotecan lactone area under the plasma concentration-time curve (AUC) of 120 to 160 ng/mL·h. After 10 patients were enrolled, the infusion was modified to 4 hours, with dosage individualization. Results: Of 36 assessable patients, four patients (11.1%) had a complete response and six (16.6%) showed a partial response, and disease was stable in 17 patients (47.2%). Toxicity was mostly hematologic, with only one patient experiencing treatment delay. The target plasma AUC was achieved in 24 of 32 studies (75%) in the 30-minute infusion group, and in 58 of 93 studies (62%) in the 4-hour infusion group. The desired CSF topotecan exposure was achieved in seven of eight pharmacokinetic studies when the topotecan plasma AUC was within target range. Conclusion: Topotecan is an effective agent against pediatric medulloblastoma in patients who have received no therapy other than surgery. Pharmacokinetically guided dosing achieved the target plasma AUC in the majority of patients. This drug warrants testing as part of standard postradiation chemotherapeutic regimens. Furthermore, these results emphasize the importance of translational research in drug development, which in this case identified an effective drug.

Idioma originalEnglish (US)
Páginas (desde-hasta)3357-3365
Número de páginas9
PublicaciónJournal of Clinical Oncology
Volumen22
N.º16
DOI
EstadoPublished - 2004
Publicado de forma externa

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Huella

Profundice en los temas de investigación de 'Results of a phase II upfront window of pharmacokinetically guided topotecan in high-risk medulloblastoma and supratentorial primitive neuroectodermal tumor'. En conjunto forman una huella única.

Citar esto