A phase II trial of high-dose bromodeoxyuridine with accelerated fractionation radiotherapy followed by procarbazine, lomustine, and vincristine for glioblastoma multiforme

Int J Radiat Oncol Biol Phys. 1999 Aug 1;45(1):127-35. doi: 10.1016/s0360-3016(99)00122-4.

Abstract

Purpose: To conduct a Phase II study to evaluate the long-term efficacy and safety of high-dose 5'-bromodeoxyuridine (BrdU) and accelerated radiotherapy followed by procarbazine, lomustine (CCNU), and vincristine (PCV) chemotherapy in patients with glioblastoma multiforme.

Methods and materials: Between 1994 and 1996, 88 patients were enrolled to receive 1.9 Gy of radiation three times a day for two 5-day cycles separated by 2 weeks; each 5-day cycle was preceded by a continuous 96-hour infusion of BrdU at a dose of 2.1 g/m2/day. After radiotherapy, patients received PCV chemotherapy.

Results: Median survival for all 88 patients was 50 weeks. Seventy (79.5 %) received one or more courses of PCV; their median survival was 57 weeks. Covariates predictive of improved survival were gross total versus subtotal resection or biopsy (p = 0.0048) and radiation dose > or = 56 Gy (p = 0.019). While receiving BrdU, 47 patients (53%) suffered grade 3 or 4 thrombocytopenia or leukopenia; 22 patients (25%) suffered grade 3 or 4 dermatologic toxicity.

Conclusion: Survival was not extended in patients with glioblastoma or gliosarcoma who received BrdU at the dose and administration schedule used in this study. The BrdU dose used in this study resulted in substantial myelosuppressive and dermatologic toxicity.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Antimetabolites, Antineoplastic / administration & dosage
  • Antimetabolites, Antineoplastic / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / pathology
  • Brain Neoplasms / radiotherapy*
  • Brain Neoplasms / surgery
  • Bromodeoxyuridine / administration & dosage
  • Bromodeoxyuridine / adverse effects
  • Cognition / drug effects
  • Cognition / radiation effects
  • Combined Modality Therapy
  • Disease Progression
  • Disease-Free Survival
  • Female
  • Glioblastoma / drug therapy*
  • Glioblastoma / pathology
  • Glioblastoma / radiotherapy*
  • Glioblastoma / surgery
  • Humans
  • Lomustine / administration & dosage
  • Lomustine / adverse effects
  • Male
  • Middle Aged
  • Procarbazine / administration & dosage
  • Procarbazine / adverse effects
  • Radiation-Sensitizing Agents / administration & dosage*
  • Radiation-Sensitizing Agents / adverse effects
  • Reoperation
  • Vincristine / administration & dosage
  • Vincristine / adverse effects

Substances

  • Antimetabolites, Antineoplastic
  • Radiation-Sensitizing Agents
  • Procarbazine
  • Vincristine
  • Lomustine
  • Bromodeoxyuridine

Supplementary concepts

  • PCV protocol