Fotemustine combined with procarbazine in recurrent malignant gliomas: a phase I study with evaluation of lymphocyte 06-alkylguanine-DNA alkyltransferase activity.

2.50
Hdl Handle:
http://hdl.handle.net/10541/85578
Title:
Fotemustine combined with procarbazine in recurrent malignant gliomas: a phase I study with evaluation of lymphocyte 06-alkylguanine-DNA alkyltransferase activity.
Authors:
Boiardi, Amerigo; Silvani, Antonio; Ciusani, Emilio; Watson, Amanda J; Margison, Geoffrey P; Berger, Elisabeth; Lucas, Catherine; Giroux, Bruno
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.
Affiliation:
Istituto Carlo Besta, Milan, Italy.
Citation:
Fotemustine combined with procarbazine in recurrent malignant gliomas: a phase I study with evaluation of lymphocyte 06-alkylguanine-DNA alkyltransferase activity. 2001, 52 (2):149-56 J. Neurooncol.
Journal:
Journal of Neuro-oncology
Issue Date:
Apr-2001
URI:
http://hdl.handle.net/10541/85578
PubMed ID:
11508814
Type:
Article
Language:
en
ISSN:
0167-594X
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorBoiardi, Amerigoen
dc.contributor.authorSilvani, Antonioen
dc.contributor.authorCiusani, Emilioen
dc.contributor.authorWatson, Amanda Jen
dc.contributor.authorMargison, Geoffrey Pen
dc.contributor.authorBerger, Elisabethen
dc.contributor.authorLucas, Catherineen
dc.contributor.authorGiroux, Brunoen
dc.date.accessioned2009-11-06T16:01:42Z-
dc.date.available2009-11-06T16:01:42Z-
dc.date.issued2001-04-
dc.identifier.citationFotemustine combined with procarbazine in recurrent malignant gliomas: a phase I study with evaluation of lymphocyte 06-alkylguanine-DNA alkyltransferase activity. 2001, 52 (2):149-56 J. Neurooncol.en
dc.identifier.issn0167-594X-
dc.identifier.pmid11508814-
dc.identifier.urihttp://hdl.handle.net/10541/85578-
dc.description.abstractThe 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.en
dc.language.isoenen
dc.subjectBrain Canceren
dc.subjectCancer Recurrenceen
dc.subject.meshAdult-
dc.subject.meshAged-
dc.subject.meshAntineoplastic Agents-
dc.subject.meshBrain Neoplasms-
dc.subject.meshFemale-
dc.subject.meshGlioma-
dc.subject.meshHumans-
dc.subject.meshLymphocytes-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.subject.meshNeoplasm Recurrence, Local-
dc.subject.meshNitrosourea Compounds-
dc.subject.meshO(6)-Methylguanine-DNA Methyltransferase-
dc.subject.meshOrganophosphorus Compounds-
dc.subject.meshProcarbazine-
dc.titleFotemustine combined with procarbazine in recurrent malignant gliomas: a phase I study with evaluation of lymphocyte 06-alkylguanine-DNA alkyltransferase activity.en
dc.typeArticleen
dc.contributor.departmentIstituto Carlo Besta, Milan, Italy.en
dc.identifier.journalJournal of Neuro-oncologyen

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