DOSE-INTENSIFICATION OF PROCARBAZINE, CCNU (LOMUSTINE), VINCRISTINE (PCV) WITH PERIPHERAL-BLOOD STEM-CELL SUPPORT IN YOUNG-PATIENTS WITH GLIOMAS

Background. The regimen of procarbazine, CCNU, and vincristine is acti ve against gliomas. Previous attempts at dose-intensification have bee n unsuccesful because of delayed and cumulative myelosuppression. We s ought to determine whether peripheral blood stem cell (PBSC) infusions would allow dose-escalation and time compression. Procedure. Eleven p atients, age 2.8-35.9 years, with newly diagnosed (n = 10) or recurren t (n = 1) gliomas underwent PBSC harvesting after mobilization with C- CSF. Chemotherapy consisted of CCNU 130 mg/m(2) on day 0, vincristine 1.5 mg/m(2) on days 0 and 7, and procarbazine 150 mg/m2 on days 1-7. P BSCs were reinfused on day 9 of each course. Four courses of chemother apy were administered 28 days apart or when counts recovered. Involved field radiation was administered to newly diagnosed high-grade glioma patients following recovery from chemotherapy. Results. Compared to t he standard PCV regimen given every 6 weeks, dose intensity received w as 1.7- and 1.8-fold greater for CCNU and procarbazine. Chemotherapy w as delivered on lime in 33/41 (80.5%) courses. Four courses (9.8%) wer e complicated by absolute neutrophil counts <200/mu L; platelet nadirs < 50,000/mu L occurred in two courses (4.9%). Fever with neutropenia complicated three courses. Eight of 9 patients with measurable disease had an objective decrease in tumor size and/or decreased enhancement. Median survival for patients with high-grade gliomas (n = 6)was 13 mo nths. Conclusions. Dose-intensification of PCV is possible using PBSCs . (C) 1998 Wiley-Liss, Inc.