Localised and unresectable neuroblastoma in infants: excellent outcome with low-dose primary chemotherapy

Abstract

The purpose of this study was to evaluate the efficacy of low-dose chemotherapy in infants with localised and unresectable neuroblastoma (NB). All consecutive infants with localised NB and no N-myc amplification were eligible in the SFOP-NBL 94 study. Primary tumour was deemed as unresectable according to imaging data showing any risk of immediate resection. Diagnostic procedures and staging were conducted according to INSS recommendations. For children, provided that they had no threatening symptom (i.e. vital risk or dumb-bell NB with neurologic deficit), chemotherapy consisted in low-dose cyclophosphamide (5 mg À1 kg day À1 Â 5 days) and vincristine (0.05 mg kg À1 at day 1) -CV and repeated one to three times every 2 weeks until surgical excision can be safely performed. No postoperative treatment was given. Between January 1995 and December 1999, 134 consecutive infants with localised NB were registered in the study, of whom 39 had an unresectable NB without N-myc amplification. Among them 28 had no threatening symptom and received CV according to the protocol. Objective response was observed in 14 (50%) and the other 14 were given second-line chemotherapy because of no response. Surgery was attempted in 38 patients including 14 after CV alone, leading to complete resection in 23. Relapses occurred in four patients all local. Survival and event-free survival were 100 and 9075% with a median follow-up of 55 months (range 33 -93). In conclusion primary low-dose chemotherapy without anthracyclines is efficient in about half of the infants presenting with an unresectable NB and no N-myc amplification, allowing excellent survival rates without jeopardising their long-term outcome even for nonresponding patients who received standard regimen.

Neuroblastoma

“…Although a portion of these patients will have disease progression after surgery, they can be salvaged with surgery or chemotherapy, or both, and achieve overall survival rates comparable to those of similar patients whose disease did not progress. [30][31][32][33][34][35][36][37][38][39][40] Observation, with serial ultrasound scans every three to six weeks, is a reasonable alternative in the following patient groups:…”

Laparostomy closure in stage 4S neuroblastoma

“…In general this has a good prognosis as spontaneous [8], or chemotherapy [9] resolution may occur. However, in the short-term stage, massive hepatomegaly may cause abdominal compartment syndrome, and an urgent decompressive laparotomy may be required [2,3].…”

Immunomodulatory effects of low dose chemotherapy and perspectives of its combination with immunotherapy

“…53 Examples of the clinical use of LDM CTX include the combination of weekly vincristine and low-dose daily CTX that was shown to be effective against neuroblastoma. 54 Combination of LDM CTX with celecoxib in heavily pretreated patients contributed to an impressive duration of stable disease with no toxicity, 45 whereas this combination is also effective in treating refractory high-grade lymphoma. 55 The combination of CTX plus weekly vinblastine and rofecoxib is effective for a subset of Hodgkin's disease patients.…”