title: Dose-intensification of procarbazine, CCNU (lomustine), vincristine (PCV) with peripheral blood stem cell support in young patients with gliomas.
abstract: BACKGROUND
  The regimen of procarbazine, CCNU, and vincristine is active against gliomas. Previous attempts at dose-intensification have been unsuccessful because of delayed and cumulative myelosuppression. We sought to determine whether peripheral blood stem cell (PBSC) infusions would allow dose-escalation and time compression.
  
  
  METHODS
  Eleven patients, age 2.8-35.9 years, with newly diagnosed (n = 10) or recurrent (n = 1) gliomas underwent PBSC harvesting after mobilization with G-CSF. Chemotherapy consisted of CCNU 130 mg/m2 on day 0, vincristine 1.5 mg/m2 on days 0 and 7, and procarbazine 150 mg/m2 on days 1-7. PBSCs were reinfused on day 9 of each course. Four courses of chemotherapy 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 the standard PCV regimen given every 6 weeks, dose intensity received was 1.7- and 1.8-fold greater for CCNU and procarbazine. Chemotherapy was delivered on time in 33/41 (80.5%) courses. Four courses (9.8%) were complicated by absolute neutrophil counts < 200/microL; platelet nadirs < 50,000/microL 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 months.
  
  
  CONCLUSIONS
  Dose-intensification of PCV is possible using PBSCs.
authors.affiliation: Department of Pediatrics, James Whitcomb Riley Hospital for Children, Indianapolis, Indiana 46202-5225, USA. rjakacki@iupui.edu
authors.forename: R I
authors.initials: RI
authors.lastname: Jakacki
authors.forename: C
authors.initials: C
authors.lastname: Jamison
authors.forename: V P
authors.initials: VP
authors.lastname: Mathews
authors.forename: D K
authors.initials: DK
authors.lastname: Heilman
authors.forename: E
authors.initials: E
authors.lastname: Dropcho
authors.forename: K
authors.initials: K
authors.lastname: Cornetta
authors.forename: D R
authors.initials: DR
authors.lastname: Macdonald
authors.forename: D A
authors.initials: DA
authors.lastname: Williams
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D005260:Female; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D008130:Lomustine / Q000008:administration & dosage; D008297:Male; D011344:Procarbazine / Q000008:administration & dosage; D016019:Survival Analysis; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D011344:Procarbazine; D014750:Vincristine; D008130:Lomustine