title: Dose-intensive, time-compressed procarbazine, CCNU, vincristine (PCV) with peripheral blood stem cell support and concurrent radiation in patients with newly diagnosed high-grade gliomas.
abstract: The dose intensity of the PCV regimen can be doubled using peripheral blood stem cell (PBSC) support. This study sought to determine the feasibility of giving dose-intensive PCV concurrently with radiation therapy. Twelve patients, age 3.2-22.7 years, median 7.5 years, with newly diagnosed high grade gliomas were enrolled. Diagnoses included diffuse intrinsic brainstem gliomas (BSG) (n = 6), glioblastoma (n = 4), anaplastic astrocytoma (n = 2). PBSCs were harvested prior to chemotherapy with G-CSF priming. Chemotherapy consisted of CCNU 130 mg/m2 and vincristine 1.5 mg/m2 on day 0, and procarbazine 150 mg/m2 on days 1-7. PBSCs were reinfused on day 9 of each course. Four courses of chemotherapy were administered every 28 days or when blood counts recovered. The first course was administered the week prior to RT, the second course began on week 3 of RT and the third and fourth course were given after RT. Hematologic toxicity was mild and the majority of courses were given on schedule. Five of six patients with diffuse BSG showed clinical improvement and three showed a radiographic response; however, only one remains alive 12+ months from diagnosis. All four patients with non-brainstem large-volume tumors showed clinical deterioration and radiographic progression during or shortly after RT. MRI scans showed massive edema and enhancement. Median time to radiographic progression was five months. Median overall survival was 11 months. We conclude that dose-intensive, time-compressed PCV given concurrently with large-volume RT appears to result in unacceptable toxicity in patients with large residual tumors.
authors.affiliation: Department of Pediatrics, James Whitcomb Riley Hospital for Children, Indianapolis, IN, USA. jakackr@chplink.chp.edu
authors.forename: R I
authors.initials: RI
authors.lastname: Jakacki
authors.forename: J
authors.initials: J
authors.lastname: Siffert
authors.forename: C
authors.initials: C
authors.lastname: Jamison
authors.forename: L
authors.initials: L
authors.lastname: Velasquez
authors.forename: J C
authors.initials: JC
authors.lastname: Allen
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005240:Feasibility Studies; D005260:Female; D005910:Glioma / Q000175:diagnosis / Q000188:drug therapy*; D006402:Hematologic Diseases / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008130:Lomustine / Q000008:administration & dosage; D008297:Male; D011344:Procarbazine / Q000008:administration & dosage; D018714:Radiotherapy, Adjuvant; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D011344:Procarbazine; D014750:Vincristine; D008130:Lomustine