Front-line topotecan and high-dose cyclophosphamide followed by ICE in high-risk neuroblastoma

Abstract

8536 Background: Treatment options for advanced neuroblastoma are still limited, but new agents have recently shown promising activity. A pilot study with front-line topotecan was started in April 2001. Methods: Two courses of topotecan 6 mg/m2 with cyclophosphamide 4.2 g/m2 (140 mg/kg) were followed by two courses of ICE (ifosfamide 9 g/m2, carboplatin 800 mg/m2 and etoposide 500 mg/m2), PBSC harvest, surgery, one course of CAV (cyclophosphamide 3 g/m2, doxorubicin 75 mg/m2 and vincristine 1.5 mg/m2), high-dose therapy with ETC (etoposide 600 mg/m2, thiotepa 750 mg/m2 and cyclophosphamide 120 mg/kg) and PBSC rescue (immunoselection), hyperfractionated local radiotherapy (21 Gy over 7 days) and CRA (160 mg/m2 for 12 months). 10 consecutive pts with high-risk neuroblastoma over one year of age have been accrued, male/female 6/4, median age 27 mos (range 13–66). 1 stage 2 (MYCNA, 1pdel), 1 stage 3 (MYCNA, 1pdel), 8 stage 4 (2 MYCNA, one 1 pdel). 3 further pts have not yet completed 2 courses. Results: Toxicity was predictable and mainly hematological. Median interval between topo-cyclo courses was 29 days (range 23–34), observed responses were 1 CR, 4 PR and 5 MR (RR 50%). Median interval between ICE courses was 31 days (range 23–39), observed responses at end of induction were 1 CR, 6 PR and 3 MR (RR 70%). 9/10 pts have performed successful PBSC harvests. After surgery we recorded 5 CR, 4 PR, while 1 pt is TETE. Median interval between PBSCT and RT was 45 days (range 31–62). After a median follow-up of 12.5 months (range 4–23), among the 7 pts who have already completed RT, we recorded 1 DOD (stage 3 MYCNA, 1pdel) 12 months after diagnosis; 3 CR (stage 4) at +23, +21 and +18 months; 1 VGPR (stage 4) at +9 months; 2 SD (stage 4) at +23 and +13 months. Conclusions: Evaluation of the first 10 pts revealed a 100% RR after induction and surgery, no toxic deaths nor PD during induction, with the potential for adequate PBSC harvests. The combination topo-cyclo and ICE was active and well tolerated with promising results in this high-risk population. The simple scheme and predictable pattern of toxicity lend themselves to the incorporation of biological response modifiers and other innovative therapies. No significant financial relationships to disclose.