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

Publication ,  Journal Article
Stewart, CF; Iacono, LC; Chintagumpala, M; Kellie, SJ; Ashley, D; Zamboni, WC; Kirstein, MN; Fouladi, M; Seele, LG; Wallace, D; Houghton, PJ ...
Published in: J Clin Oncol
August 15, 2004

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.

Duke Scholars

Published In

J Clin Oncol

DOI

ISSN

0732-183X

Publication Date

August 15, 2004

Volume

22

Issue

16

Start / End Page

3357 / 3365

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Topotecan
  • Risk Factors
  • Oncology & Carcinogenesis
  • Neuroectodermal Tumors, Primitive
  • Medulloblastoma
  • Male
  • Infusions, Intravenous
  • Humans
  • Female
 

Citation

APA
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ICMJE
MLA
NLM
Stewart, C. F., Iacono, L. C., Chintagumpala, M., Kellie, S. J., Ashley, D., Zamboni, W. C., … Gajjar, A. (2004). Results of a phase II upfront window of pharmacokinetically guided topotecan in high-risk medulloblastoma and supratentorial primitive neuroectodermal tumor. J Clin Oncol, 22(16), 3357–3365. https://doi.org/10.1200/JCO.2004.10.103
Stewart, Clinton F., Lisa C. Iacono, Murali Chintagumpala, Stewart J. Kellie, David Ashley, W. C. Zamboni, M. N. Kirstein, et al. “Results of a phase II upfront window of pharmacokinetically guided topotecan in high-risk medulloblastoma and supratentorial primitive neuroectodermal tumor.J Clin Oncol 22, no. 16 (August 15, 2004): 3357–65. https://doi.org/10.1200/JCO.2004.10.103.
Stewart CF, Iacono LC, Chintagumpala M, Kellie SJ, Ashley D, Zamboni WC, et al. Results of a phase II upfront window of pharmacokinetically guided topotecan in high-risk medulloblastoma and supratentorial primitive neuroectodermal tumor. J Clin Oncol. 2004 Aug 15;22(16):3357–65.
Stewart, Clinton F., et al. “Results of a phase II upfront window of pharmacokinetically guided topotecan in high-risk medulloblastoma and supratentorial primitive neuroectodermal tumor.J Clin Oncol, vol. 22, no. 16, Aug. 2004, pp. 3357–65. Pubmed, doi:10.1200/JCO.2004.10.103.
Stewart CF, Iacono LC, Chintagumpala M, Kellie SJ, Ashley D, Zamboni WC, Kirstein MN, Fouladi M, Seele LG, Wallace D, Houghton PJ, Gajjar A. Results of a phase II upfront window of pharmacokinetically guided topotecan in high-risk medulloblastoma and supratentorial primitive neuroectodermal tumor. J Clin Oncol. 2004 Aug 15;22(16):3357–3365.

Published In

J Clin Oncol

DOI

ISSN

0732-183X

Publication Date

August 15, 2004

Volume

22

Issue

16

Start / End Page

3357 / 3365

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Topotecan
  • Risk Factors
  • Oncology & Carcinogenesis
  • Neuroectodermal Tumors, Primitive
  • Medulloblastoma
  • Male
  • Infusions, Intravenous
  • Humans
  • Female