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 unsuccesful because of delayed and cumulative myelosuppression. We sought to determine whether peripheral blood stem cell (PBSC) infusions would allow dose‐escalation and time compression. Procedure 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/μL; platelet nadirs < 50,000/μL 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. Med. Pediatr. Oncol. 31:483–490, 1998. © 1998 Wiley‐Liss, Inc.

Efficacy and feasibility of standard procarbazine, lomustine, and vincristine chemotherapy in anaplastic oligodendroglioma and oligoastrocytoma recurrent after radiotherapy

“…The optimum dose intensity should be a mathematic expression derived from two known constants-optimum total drug and optimum duration of treatment-and the administration of low delayed dose PCV can enhance drug resistance. 21 It is important to note that in the current study, notwithstanding the decrease of relative dose intensity, PCV chemotherapy was found to have a high response rate and TTP, in keeping with the findings made in two studies 22,23 that failed to demonstrate that a drug dosage increase in patients with AO and AOA was followed by a better outcome. The question of whether it is more useful to use temozolomide or PCV as the first-line chemotherapy is widely debated because the latter most likely has a greater activity, but also a greater toxicity, which is sometimes persistent, FIGURE 1.…”

Treatment of diffuse intrinsic brainstem gliomas: failed approaches and future strategies

“…6,13,44,54,74,83,97,114 One of these, a study that included 6 patients with diffuse brainstem gliomas, investigated concurrent radiotherapy and dose-intensive chemotherapy with procarbazine, lomustine, and vincristine. 54 The median overall survival was 11 months.…”

A pilot study of dose-intensified procarbazine, CCNU, vincristine for poor prognosis brain tumors utilizing fibronectin-assisted, retroviral-mediated modification of CD34+ peripheral blood cells with O6-methylguanine DNA methyltransferase

“…29 We have previously shown that adding stem cell support to intensive PCV using unmodified cells enabled administration of chemotherapy cycles every 4 weeks in the majority of subjects. 19 We now show that stem cell support using transduced cells in the context of intensified PCV regimen also allowed chemotherapy administration every 4 weeks in the majority of subjects. Thus, ex vivo manipulated and gene-modified cells functioned in a manner similar to unmanipulated PBPC.…”

“…The treatment schema is depicted in Figure 1 and is based on our previously reported use of involved field radiation therapy and four cycles of dose-intensified procarbazine, CCNU and vincristine (PCV) with peripheral blood stem cell support without gene transduction. 19 Peripheral blood stem cell mobilization was accomplished prior to the first cycle of chemotherapy with 4 days of granulocyte colony-stimulating factor (G-CSF) (Amgen, Thousand Oaks, CA) at 10 mcg/kg/day subcutaneously. Leukopheresis was performed with a COBE Spectra Cell Separator (COBE Laboratories, Lakewood, CO).…”