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

Abstract

BACKGROUNDA 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.METHODSChildren 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.RESULTSTwenty‐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.CONCLUSIONSThe topotecan‐vincristine‐doxorubicin combination was active and well tolerated in previously treated patients with advanced neuroblastoma. Cancer 2003. © 2003 American Cancer Society.

Busulfan–melphalan in high-risk neuroblastoma: the 30-year experience of a single institution

“…1,[34][35][36] It is noteworthy that the criteria required to receive HDC differed from those applied in the HR-NBL1/SIOPEN trial. We included patients with a CR or PR of metastases after several lines of chemotherapy ('poor response'), whereas in the SIOPEN study eligibility criteria after Rapid COJEC induction (±2 courses of topotecan with vincristine and doxorubicin) 13,37 were a CR of BM and a PR on MIBG scan with ⩽ 3 residual positive spots.…”

N-(4-Hydroxyphenyl)retinamide-induced apoptosis triggered by reactive oxygen species is mediated by activation of MAPKs in head and neck squamous carcinoma cells

“…Specifically, treatment of the 22B cells with 5 mM 4HPR resulted in caspase-3 activation and PARP cleavage after 24 h. Some apoptosis could also be detected in cells treated with 1 mM 4HPR, albeit after 48 h. Therefore, we decided to use 24 h treatment with 5 mM 4HPR for evaluation of apoptosis in subsequent experiments. It is noteworthy that 12.9 mM concentration can be achieved pharmacologically in pediatric neuroblastoma patients receiving oral 4HPR (Garaventa et al, 2003).…”

Hitherto unseen survival in an ALK‐positive‐patient with advanced stage adult ganglioneuroblastoma treated with personalized medicine

“…For relapsed disease, topotecan and temozolomide have shown effect 8, 9. Over the last decade, tyrosine kinase inhibitors (TKIs) have been developed to target specific pathways associated with tumor growth.…”