Children affected by advanced neuroblastoma have a discouraging prognosis, but intensive induction chemotherapy may increase the complete response rate. The combination of ifosfamide, carboplatin and etoposide (ICE) was used for the first time as front‐line regimen in patients with stage 4 neuroblastoma over the age of 1 y. Similarly, second‐line treatment for children with relapsed neuroblastoma, particularly after high‐dose chemotherapy, has been unsatisfactory. The combination of topotecan and cyclophosphamide was studied in resistant or relapsed solid tumors. Furthermore, there is a need for effective palliative treatment in patients failing therapy. Temozolomide, a new dacarbazine analog with optimal oral bioavailability, is being used in an ongoing phase II study as an alternative to oral etoposide. Seventeen patients with stage 4 neuroblastoma have entered the ICE study; 15/16 (94%) major responses after induction were observed and 6/16 (37%) evaluable patients are disease free after a median of 51 mo. Twenty‐one patients with relapsed/refractory disease (of whom 13 neuroblastomas) entered the topotecan/cyclophosphamide study: 7/21 (33%) patients responded. Forty‐one patients entered the temozolomide study (of whom 16 had neuroblastomas): stable disease and symptom relief were obtained in 15/30 (50%) evaluable patients. Intensive induction with ICE resulted in a faster response with high response rate; a larger study with longer follow‐up is needed to confirm a survival advantage. Second‐line treatment was effective in obtaining remissions, some of them long lasting. Third‐line treatment did not elicit measurable responses in neuroblastoma, but achieved prolonged freedom from disease progression and excellent palliation in several patients.
This retrospective review confirms a curable strategy based on local treatment and conventional plus high-dose chemotherapy. Patients with CNS involvement remain incurable.
We report the toxicity of high-dose chemotherapy (HDC) based on etoposide, thiotepa and CY (ETC) in children with poor-prognosis Ewing's sarcoma family tumors (ESFTs). A total of 26 patients with high-risk ESFT (metastasis or axis localization or tumor volume 4200 ml or necrosis o95%) were reviewed. The conditioning was based on etoposide (600 mg/m 2 ), thiotepa (750 mg/m 2 ) and CY (120 mg/kg) followed by autologous BM or PBSC rescue. The conditioning regimen was well tolerated, without any toxic deaths. The median time from transplant to a neutrophil count of 40.5 Â 10 9 /l was 10 days (range 6-27) and 22.5 days (range 9-114) for a plt count of 450 Â 10 9 /l. Oral mucositis was recorded in 20 patients, grade 1/2 in 19 and grade 3 in the last patient. Diarrhea grade 1/2 was recorded in four patients and grade 1/2 liver toxicity in four patients. Sepsis was documented in four cases and skin toxicity in three. Lung and tubular toxicity, respectively, were reported in one patient each. We conclude that the ETC regimen presented a limited and manageable toxicity. Further studies would confirm the role of ETC in high-risk ESFT.
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