Feasibility of sequential high-dose chemotherapy and peripheral blood stem cell support for pediatric central nervous system malignancies

Abstract

Background The outlook for many brain tumors remains poor. Increased dose intensity has been correlated with response rate and survival in many solid tumors. Patients and Methods Ten children with recurrent or newly diagnosed brain tumors were treated with four sequential courses of high‐dose single agent chemotherapy with peripheral blood stem cell (PBSC) support. PBSC harvesting was undertaken prior to chemotherapy and following the first course of chemotherapy (3.6 g/m2 etoposide). Each course of chemotherapy consisted of a single drug followed 48 hours later by PBSC reinfusion. Three patients were treated on Regimen A: etoposide, carboplatinum 1.95 g/m2, cyclophosphamide 5 g/m2, and thiotepa 300 mg/m2; three patients were treated on Regimen A′ with carmustine 600 mg/m2 replacing cyclophosphamide; four patients received Regimen B: etoposide, carboplatinum 1.95g/m2, cyclophosphamide 7 g/m2, and thiotepa 900 mg/m2. Results No course of chemotherapy was complicated by >14 days of neutropenia. Platelet recovery was more prolonged, particularly in patients who had previously received craniospinal irradiation. Non‐hematologic toxicity was severe with three toxic deaths including two patients who developed hemolytic‐uremic syndrome and respiratory failure. Two of three patients with primitive neuroectodermal tumors had a partial response; no responses were observed in patients with high‐grade gliomas. Conclusions Administration of multiple courses of high‐dose chemotherapy with PBSC support is feasible in this patient population and successfully mitigates hematologic toxicity. Non‐hematologic toxicity becomes prohibitive as chemotherapy doses are escalated. Med. Pediatr. Oncol. 29:553–559, 1997. © 1997 Wiley‐Liss, Inc.

Autologous hematopoietic stem cell transplantation for high-risk brain tumors in children

“…The fact that they had higher tumor load with macroscopic residual disease also made them less likely to be cured by a single course of megatherapy and AHSCT. Other investigators have therefore tried to optimize the response by applying multiple sequential courses of megatherapy followed by repeated AHSCT [28][29][30]. Whether this intensive approach can result in better long-term survival without much added toxicity remains to be answered in future prospective longterm studies.…”

Sequential chemotherapy, high-dose thiotepa, circulating progenitor cell rescue, and radiotherapy for childhood high-grade glioma

“…Multiple cycles of high-dose chemotherapy followed by PBPC support can be effi cacious in reducing tumor burden. The use of single drugs, while maintaining effi cacy, could reduce transplant-related complications (Finlay et al, 1997;Jakacki et al, 1997). No transplant-related death occurred, even under our intense conditioning regimen.…”

Adaptive dosing and platinum–DNA adduct formation in children receiving high-dose carboplatin for the treatment of solid tumours

“…Although an evaluation of clinical response data was not included in this study, owing to the potential influence of concomitant chemotherapy, it is encouraging that no treatment-related deaths were observed in any of the patients on the current study. This is particularly the case in light of the high incidence of treatment-related deaths previously reported with the use of high-dose carboplatin in paediatric patients (Santana et al, 1992;Jakacki et al, 1997;Dunkel et al, 1998).…”