A phase II study of topotecan with vincristine and doxorubicin in children with recurrent/refractory neuroblastoma
- 17 November 2003
- Vol. 98 (11), 2488-2494
- https://doi.org/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/m2 (the dose was 0.75 mg/m2 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/m2 vincristine and 45 mg/m2 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. Cancer 2003. © 2003 American Cancer Society.Keywords
This publication has 27 references indexed in Scilit:
- Disseminated Neuroblastoma in Children Older Than One Year at Diagnosis: Comparable Results With Three Consecutive High-Dose Protocols Adopted by the Italian Co-Operative Group for NeuroblastomaJournal of Clinical Oncology, 2003
- Pilot study of topotecan and high-dose cyclophosphamide for resistant pediatric solid tumorsMedical and Pediatric Oncology, 2000
- Treatment of High-Risk Neuroblastoma with Intensive Chemotherapy, Radiotherapy, Autologous Bone Marrow Transplantation, and 13-cis-Retinoic AcidNew England Journal of Medicine, 1999
- Topotecan – A Novel Topoisomerase I Inhibitor: Pharmacology and Clinical ExperienceOncology, 1999
- Relationship Between Topotecan Systemic Exposure and Tumor Response in Human Neuroblastoma XenograftsJNCI Journal of the National Cancer Institute, 1998
- Chemotherapy for Patients with Recurrent or Refractory Neuroblastoma: A POG Phase II StudyJournal of Pediatric Hematology/Oncology, 1997
- Phase I Trial and Pharmacokinetic (PK) and Pharmacodynamics (PD) Study of Topotecan Using a Five-Day Course in Children with Refractory Solid TumorsJournal of Pediatric Hematology/Oncology, 1996
- Cyclophosphamide/doxorubicin vs. Cisplatin/teniposide in the treatment of children older than 12 months of age with disseminated neuroblastoma: A pediatric oncology group randomized phase II studyMedical and Pediatric Oncology, 1995
- Experimental studies on biochemical modulation targeting topoisomerase I and II in human tumor xenografts in nude miceInternational Journal of Cancer, 1992