Background: The aim of this phase I study was to define the maximum tolerated dose (MTD) of thiotepa (TT), administered with busulfan (BU) 480 mg/m(2) and etoposide 2,400 mg/m(2), followed by autologous bone marrow transplantation (ABMT) or peripheral blood stem cell transplantation (APBSCT) support in children with solid tumors either disseminated at diagnosis or after relapse. Procedure: Nineteen patients, between 2 and 16 years of age, received a high-dose chemotherapy regimen including escalating doses of TT starting from 150 mg/m(2). Subsequent dose escalation was determined by a modified Fibonacci scheme. Whenever one patient at one dosage level showed a grade III or grade IV reversible toxicity, additional patients were admitted (one by one) up to a maximum number of 6. Upon observing grade III or IV reversible toxicity in two or more systems, in 3 of the 6 patients, no further escalation was performed, and the corresponding dosage was taken as the MTD. WHO criteria were adopted to assess grade of toxicity. Results: All patients had hematological recovery; and neutrophils and platelet engraftment were observed after median times of 12 and 29 days from stem cell infusion, respectively. The MTD of TT was determined to be 750 mg/ m(2). At this level, 3 of 6 patients experienced grade III mucositis and/or grade III gastrointestinal toxicity. No patient died of treatment-related toxicity. Conclusions: A dose of 750 mg/m(2) TT is the MTD when it is associated with BU 480 mg/m(2) and etoposide 2, 400 mg/m(2). This ablative regimen represents a feasible and tolerable combination for high-dose chemotherapy followed by hematopoietic stem cell rescue (HSCR). Phase II studies in children with poor-prognosis solid tumors are required to evaluate the effectiveness of this treatment.
Pession, A., Prete, A., Locatelli, F., Bella, S., Melchionda, F., Garaventa, A., Burnelli, R., Paolucci, G., Phase I study of high-dose thiotepa with busulfan, etoposide, and autologous stem cell support in children with disseminated solid tumors, <<MEDICAL AND PEDIATRIC ONCOLOGY>>, 1999; 33 (5): 450-454. [doi:10.1002/(sici)1096-911x(199911)33:5<450::aid-mpo3>3.0.co;2-l] [https://hdl.handle.net/10807/263697]
Phase I study of high-dose thiotepa with busulfan, etoposide, and autologous stem cell support in children with disseminated solid tumors
Locatelli, Franco;
1999
Abstract
Background: The aim of this phase I study was to define the maximum tolerated dose (MTD) of thiotepa (TT), administered with busulfan (BU) 480 mg/m(2) and etoposide 2,400 mg/m(2), followed by autologous bone marrow transplantation (ABMT) or peripheral blood stem cell transplantation (APBSCT) support in children with solid tumors either disseminated at diagnosis or after relapse. Procedure: Nineteen patients, between 2 and 16 years of age, received a high-dose chemotherapy regimen including escalating doses of TT starting from 150 mg/m(2). Subsequent dose escalation was determined by a modified Fibonacci scheme. Whenever one patient at one dosage level showed a grade III or grade IV reversible toxicity, additional patients were admitted (one by one) up to a maximum number of 6. Upon observing grade III or IV reversible toxicity in two or more systems, in 3 of the 6 patients, no further escalation was performed, and the corresponding dosage was taken as the MTD. WHO criteria were adopted to assess grade of toxicity. Results: All patients had hematological recovery; and neutrophils and platelet engraftment were observed after median times of 12 and 29 days from stem cell infusion, respectively. The MTD of TT was determined to be 750 mg/ m(2). At this level, 3 of 6 patients experienced grade III mucositis and/or grade III gastrointestinal toxicity. No patient died of treatment-related toxicity. Conclusions: A dose of 750 mg/m(2) TT is the MTD when it is associated with BU 480 mg/m(2) and etoposide 2, 400 mg/m(2). This ablative regimen represents a feasible and tolerable combination for high-dose chemotherapy followed by hematopoietic stem cell rescue (HSCR). Phase II studies in children with poor-prognosis solid tumors are required to evaluate the effectiveness of this treatment.
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