A phase II study of topotecan with vincristine and doxorubicin in children with recurrent/refractory neuroblastoma

Cancer. 2003 Dec 1;98(11):2488-94. doi: 10.1002/cncr.11797.

Abstract

Background: A Phase II trial in children with advanced neuroblastoma was carried out in five Italian institutions to evaluate the antitumor activity and tolerability of topotecan followed by vincristine and doxorubicin.

Methods: Children older than age 1 year with Stage III or Stage IV neuroblastoma, all of whom had been treated previously with chemotherapy and were diagnosed with either refractory or recurrent disease, were treated with topotecan at an intravenous dose of 1.5 mg/m(2) (the dose was 0.75 mg/m(2) for patients who were treated within 1 year of previous megatherapy) per day for 5 days followed by 48-hour intravenous infusions of 2 mg/m(2) vincristine and 45 mg/m(2) doxorubicin. Cycles of therapy were repeated every 3 weeks.

Results: Twenty-five patients (2 with Stage III disease and 23 with Stage IV disease; 19 with refractory disease and 6 with recurrent disease) were treated with a total of 115 cycles. Four patients had complete responses, 12 patients had partial responses, 4 patients had minor responses or stable disease, and 5 patients had tumor progression. The overall response rate (including complete and partial responses) was 64% (95% confidence interval, 43-82%). Fifteen patients were alive at the time of the current report and were progression free at 4-16 months (median, 9 months) after the first course of this treatment. Toxicity generally was limited to the hematopoietic system. Dose-limiting toxicity was observed in only 1 patient (Grade 4 liver toxicity). There were no deaths due to infectious or toxic causes.

Conclusions: The topotecan-vincristine-doxorubicin combination was active and well tolerated in previously treated patients with advanced neuroblastoma.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Child
  • Child, Preschool
  • Disease Progression
  • Doxorubicin / administration & dosage
  • Female
  • Humans
  • Infant
  • Male
  • Neuroblastoma / drug therapy*
  • Neuroblastoma / pathology
  • Survival Analysis
  • Topotecan / administration & dosage
  • Treatment Outcome
  • Vincristine / administration & dosage

Substances

  • Vincristine
  • Topotecan
  • Doxorubicin