High-dose carmustine, thiotepa and etoposide followed by autologous bone marrow rescue for the treatment of high risk central nervous system tumors

Forty-two patients (29 newly diagnosed) with high grade gliomas (II = 37), medulloblastoma (n = 2) or non-biopsied tumors (n=3) with supratentorial (n =24), brain stem (n = 11), posterior fossa (n=5) or spinal (n=2) location m ere eligible for this study with adequate organ function and no bone marrow tumor infiltration. Median patient age was 12.2 years (range, 0.7-46.8), A total of 600 mg/m(2) BCNU, 900 mg/m(2) thiotepa and 1500 or 750 mg/m(2) et oposide (VP-16) was administered followed by autologous bone marrow reinfus ion (ABMR). Twenty-one newly diagnosed patients received local irradiation (RT) post ABMR. Nine early deaths were observed (21%), as well as one secon dary graft failure. Half of the patients aged 18 years or older experienced toxic deaths, whereas only 15% of patients younger than 18 years experienc ed toxic death (P = 0.05), Of 25 evaluable newly diagnosed patients, 20% ac hieved complete remission (CR) and 4% partial remission (PR), while 28% rem ained in continuing complete remission (CCR) and 44% remained with stable d isease prior to RT, Of eight evaluable patients with recurrent disease, one achieved CR and two PR, while one remained in CCR and four with stable dis ease for 1 to 110.2 months. Overall survival was 36%, 24% and 17% at 1, 2 a nd 3 years following ABMR, with three newly diagnosed patients and one pati ent treated for recurrent disease being alive, without disease progression 64.4, 67.0, 86.3 and 110.2 months after ABMR, respectively. The combination of high-dose BCNU/thiotepa/VP-16 has substantial toxicity but definite act ivity for high risk CNS tumors. Similar protocols with lower toxicity merit further evaluation in both newly diagnosed and recurrent CNS tumors.