Oral etoposide for refractory and relapsed neuroblastoma

Purpose: To describe the efficacy of oral etoposide against resistant stage 4 neuroblastoma. Patients and Methods: Patients with refractory or recurrent stage 4 neurobl astoma were treated with etoposide 50 mg/m(2) taken orally each day, in two or three divided doses, for 21 consecutive days. Treatment could be repeat ed after a 1-week period. Extent-of-disease studies included imaging with 1 31-iodine-metaiodobenzylguanidine and extensive bone marrow (BM) sampling. Results: Oral etoposide was used in 20 children between the ages of 2 and 1 1 years (median, 6 years), Prior treatment included high doses of alkylatin g agents and a median of 4.5 cycles of etoposide-containing chemotherapy, w ith cumulative etoposide doses of 1,800 mg/m(2) to 3,935 mg/m(2) (median, 2 ,300 mg/m(2)). Oral etoposide produced antineuroblastoma effects in four of four children with disease refractory to intensive induction treatment; sa mpling variability could account for resolution (n = 3) or reduction (n = 1 ) of PM involvement, but improvement in other markers also occurred, Antine uroblastoma effects were also evident in five of five children with asympto matic relapses after a long chemotherapy-free interval: PM disease resolved and all other disease markers significantly improved in two patients, and disease markers improved or stabilized in three patients on treatment for m ore than 6 months, In these nine patients, extramedullary toxicity was abse nt, neutropenia did not occur, transfusional support was nat needed, and pr eliminary data suggested little immunosuppression (phytohemagglutinin respo nses). Oral etoposide was ineffective in all (11 of 11) patients with rapid ly growing tumor masses. Conclusion: Given the absence of toxicity to major organs, the minimal myel osuppression or immunosuppression, and the antineoplastic activity in patie nts with low tumor burdens after high-dose chemotherapy, limited use of low -dose oral etoposide should be considered for inclusion in postinduction co nsolidative treatment programs aimed at eradicating minimal residual diseas e. (C) 1999 by American Society of Clinical Oncology.