Journal of Neuro-Oncology 44: 77–83, 1999. © 1999 Kluwer Academic Publishers. Printed in the Netherlands. Clinical Study 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 Regina I. Jakacki 1 , Joao Siffert 2 , Cheryl Jamison 1 , Linda Velasquez 2 and Jeffrey C. Allen 2 1 Section of Pediatric Neuro-Oncology, Department of Pediatrics, James Whitcomb Riley Hospital for Children, Indianapolis, IN, USA; 2 Department of Neurology, Beth Israel Medical Center North, New York, NY, USA Key words: gliomas, procarbazine, CCNU, dose intensity, peripheral blood stem cells, chemoradiotherapy Summary 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/m 2 and vincristine 1.5 mg/m 2 on day 0, and procarbazine 150 mg/m 2 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. Introduction Despite increasingly aggressive use of both chemother- apy and radiation therapy, the prognosis for patients with malignant gliomas remains poor [1,2]. Although both radiation therapy and chemotherapy prolong sur- vival times, less than 20% of children with glioblas- tomas are alive five years after diagnosis [2,3]. A nitrosourea-based regimen is considered by many to be standard chemotherapy for patients with high-grade gliomas. The PCV regimen of procar- bazine, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) and vincristine is the only combination regi- men shown to be more effective than BCNU alone in a randomized clinical trial in adults [4]. Dose intensity, defined as the amount of drug delivered per unit of time, has been correlated with both response and survival in various malignancies [5]. Due to delayed myelosup- pression seen with both procarbazine and CCNU, a six- week interval is usually required for marrow recovery. We have shown that the ‘dose-intensive’ PCV regimen (using higher doses of procarbazine and CCNU) can be given every four weeks with the use of peripheral blood stem cell (PBSC) support, allowing a doubling of the dose intensity compared to the standard regimen [6]. Historically, radiation therapy is the most effective treatment modality for gliomas. Certain chemotherapy agents may potentiate the effect of the radiation when given concurrently. Both in vitro studies as well as ani- mal tumor models have shown that the combination of