Fotemustine combined with procarbazine in recurrent malignant gliomas: A phase I study with evaluation of lymphocyte O6-alkylguanine-DNA alkyltransferase activity

A. Boiardi, A. Silvani, E. Ciusani, A. Watson, G. Margison, E. Berger, C. Lucas, B. Giroux

Research output: Contribution to journalArticle

Abstract

The aims of this phase I study in patients with recurrent malignant gliomas were to determine the maximum tolerated dose (MTD) and toxicity profile of fotemustine when combined with a fixed dose of procarbazine (PCZ), and to evaluate the extent of O6-alkylguanine-DNA alkyltransferase (ATase) depletion in circulating lymphocytes during treatment. Sixteen patients received an induction cycle consisting of 100 mg/day oral PCZ for 12 consecutive days and a 1-h intravenous infusion of fotemustine given 4 h after PCZ on days 5 and 12 at escalated doses (50, 75, 100 and 125 mg/m2/day). After a 6-week rest period, a maximum of 4 maintenance cycles (PCZ 300 mg/day, 4 days; fotemustine, day 4) was given every 4 weeks. ATase activity was measured on days 1, 5 and 12 over 4 h after PCZ intake. Fifteen patients had previously received at least one nitrosourea-based chemotherapy, associated with PCZ in 12 cases. The MTD of fotemustine was 125 mg/m2 (days 5 and 12) with myelosuppression as the dose limiting toxicity (DLT). At this dose level, half of patients experienced grade 3 anemia, neutropenia or thrombopenia. No extra-hematological DLT was observed. No significant depletion of ATase activity by PCZ was evidenced. One partial response and 7 stable diseases were obtained leading to a disease control rate of 50%. The median times to progression and survival were 2.6 and 9.7 months, respectively. This combined regimen of PCZ and fotemustine was well tolerated with a good disease control rate in heavily pretreated glioma patients and merits further investigation in phase II studies.

Original languageEnglish
Pages (from-to)149-156
Number of pages8
JournalJournal of Neuro-Oncology
Volume52
Issue number2
DOIs
Publication statusPublished - 2001

Fingerprint

fotemustine
Procarbazine
Glioma
Lymphocytes
Alkyl and Aryl Transferases
Maximum Tolerated Dose
DNA alkyltransferase
Neutropenia
Intravenous Infusions
Thrombocytopenia
Anemia

Keywords

  • Fotemustine
  • Malignant glioma
  • O-alkylguanine-DNA alkyltransferase
  • Phase I study
  • Procarbazine

ASJC Scopus subject areas

  • Clinical Neurology
  • Cancer Research
  • Oncology
  • Neuroscience(all)

Cite this

Fotemustine combined with procarbazine in recurrent malignant gliomas : A phase I study with evaluation of lymphocyte O6-alkylguanine-DNA alkyltransferase activity. / Boiardi, A.; Silvani, A.; Ciusani, E.; Watson, A.; Margison, G.; Berger, E.; Lucas, C.; Giroux, B.

In: Journal of Neuro-Oncology, Vol. 52, No. 2, 2001, p. 149-156.

Research output: Contribution to journalArticle

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