Excellent Outcome With Reduced Treatment in Infants With Nonmetastatic and Unresectable Neuroblastoma Without MYCN Amplification: Results of the Prospective INES 99.1

PurposeTo evaluate the efficacy of low-dose chemotherapy in infants with nonmetastatic and unresectableneuroblastoma (NB) without MYCN amplification.Patients and MethodsInfants with localized NB and no MYCN amplification were eligible in the SIOPEN InfantNeuroblastoma European Study 99.1 study. Primary tumor was deemed unresectable according toimaging defined risk factors. Diagnostic procedures and staging were carried out according toInternational Staging System recommendations. Children without threatening symptoms receivedlow-dose cyclophosphamide (5 mg/kg/d 5 days) and vincristine (0.05 mg/kg at day 1; CyV),repeated once to three times every 2 weeks until surgical excision could be safely performed.Children with either one threatening symptom or insufficient response to CyV were givencarboplatin and etoposide (CaE), sometimes followed by vincristine, cyclophosphamide, anddoxorubicin. No postoperative treatment was to be administered.ResultsBetween December 1999 and April 2004, 120 infants were included in the study. Eighty-eight hadno threatening symptoms and 79 received CyV. CaE was given to 49 of them because ofinsufficient response. Thirty-two children had threatening symptoms, 30 of whom received CaE.Anthracyclines were given to 46 children. Surgery was attempted in 102 patients, leading to grosssurgical excision in 93. Relapse occurred in 12 patients (nine local and three metastatic). Five-yearoverall and event-free survivals were 99% 1% and 90% 3%, respectively, with a medianfollow-up of 6.1 years (range, 1.6 to 9.1).ConclusionLow-dose chemotherapy without anthracyclines is effective in 62% of infants with an unresectableNB and no MYCN amplification, allowing excellent survival rates without jeopardizing theirlong-term outcome.