Improved response in high-risk neuroblastoma with protracted topotecan administration using a pharmacokinetically guided dosing approach

Victor M. Santana, Wayne L. Furman, Catherine A. Billups, Fredric Hoffer, Andrew M. Davidoff, Peter J. Houghton, Clinton F. Stewart

Research output: Contribution to journalArticle

64 Scopus citations

Abstract

Purpose: To estimate the response rate and toxicity associated with intravenous topotecan when it is administered on a protracted schedule according to a pharmacokinetically guided dosing approach to treat childhood high-risk neuroblastoma. Patients and Methods: In this prospective phase II trial, topotecan was administered intravenously daily for 5 days for each of 2 consecutive weeks for two cycles. On the basis of topotecan systemic clearance, doses were individualized to attain a single-day topotecan lactone area under the plasma concentration-time curve (AUC) of 80 to 120 ng/mL · h. Patients subsequently received standard treatment. Results: Both cycles were administered to 28 (93%) of the 30 enrolled patients (median age, 3.1 years). Target topotecan AUCs were achieved in 92 (72%) of the 127 measurements conducted after pharmacokinetically guided adjustment; the median dosage required to achieve target AUCs was 2.7 mg/m2 (range, 0.95 to 3.8 mg/m2). The response rate was 60% (95% CI, 41 % to 77%); there were one complete and 17 partial responses. No patient experienced disease progression during initial topotecan therapy. Primary tumor volumes decreased (median decrease, -58.2%; range, -95.1% to -4.9%) in the 26 patients with available size data. Homovanillic acid levels in 16 (89%) of 18 patients and vanillylmandelic acid levels in 14 (78%) of 18 patients were lower (P = .002 and P = .018, respectively) after topotecan therapy. Reversible grade 4 myelosuppression occurred in all patients, but no deaths occurred as a result of infection or toxicity. Conclusion: Topotecan is active against neuroblastoma when it is administered on a protracted schedule and targeted systemic exposure is achieved.

Original languageEnglish (US)
Pages (from-to)4039-4047
Number of pages9
JournalJournal of Clinical Oncology
Volume23
Issue number18
DOIs
StatePublished - 2005
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Improved response in high-risk neuroblastoma with protracted topotecan administration using a pharmacokinetically guided dosing approach'. Together they form a unique fingerprint.

  • Cite this