Toxicity of high-dose chemotherapy with etoposide, thiotepa and CY in treating poor-prognosis Ewing's sarcoma family tumors: the experience of the Bambino Gesù Children's Hospital

Abstract

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.

High-dose Thiotepa as Consolidation Therapy With Autologous Hematopoietic Stem Cell Transplantation for High-risk Ewing Family Tumors

“…19 This high total dose (900 mg/m 2 ) combined with carboplatin and etoposide yielded in the present study a comparable low toxicity, but slightly better 10-year OS (73%) compared with a lower total dose (750 mg/m 2 ) combined with etoposide and cyclophosphamide as reported in one earlier study (7-y OS 64%). 22 Importantly, both studies support the fact that RT to axial sites can be given safely in combination to HDTx.…”

“…This compares favorably to the 5-year OS of 44% for first remission Ewing sarcomas reported by European Organization of Blood and Marrow Transplantation 7 and the 7-year OS of 64% for Ewing sarcomas treated with thiotepa-based HDTx. 22 In the cohort of 24 patients, 4 patients relapsed. Three of them were transplanted after relapse, and one of these became a long-term survivor (currently 12 y) after a single thiotepabased HDTx.…”

“…25,26 There is also encouraging experience of HD-thiotepa in various pediatric solid tumors. [20][21][22]27 Published studies point out its remarkable safety with very low nonhematological toxicity in heavily pretreated patients or inpatients who are at high risk of treatment-related toxicity. Nonhematological side effects are mainly observed in the gastrointestinal system and the extramedullary toxicity of HD-thiotepa is acceptable or mild even in repeat doses or when combined with, for example, etoposide and carboplatin.…”

“…Nonhematological side effects are mainly observed in the gastrointestinal system and the extramedullary toxicity of HD-thiotepa is acceptable or mild even in repeat doses or when combined with, for example, etoposide and carboplatin. 22 The highest dosage for combination therapy has been 900 mg/m 2 . 19 This high total dose (900 mg/m 2 ) combined with carboplatin and etoposide yielded in the present study a comparable low toxicity, but slightly better 10-year OS (73%) compared with a lower total dose (750 mg/m 2 ) combined with etoposide and cyclophosphamide as reported in one earlier study (7-y OS 64%).…”

“…20,21 There are, however, only few studies concerning the effect of thiotepa in high-risk Ewing tumors. 22 In the present report, we describe our singleinstitution experience of single and tandem HDTx in pediatric Ewing family tumors, with special emphasis on high-dose (HD) thiotepa (900 mg/m 2 ) as the backbone of our HD-regimen.…”