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Treatment
> Temozolomide
Clinical Trials
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J Neurooncol. 2006 Nov 3; [Epub
ahead of print]. DOI: 10.1007/s11060-006-9280-4
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Abstract |
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Toxicity and efficacy of protracted low
dose temozolomide for the treatment of low grade gliomas Nader Pouratian1*,
Jaime Gasco1, Jonathan H. Sherman1,
Mark E. Shaffrey1 and David Schiff1,
2, 3 1Department
of Neurological Surgery, University of Virginia, Box 800212,
Charlottesville, VA 22908-0212, USA. 2Department
of Neurology, University of Virginia, Charlottesville, VA, USA. 3Department
of Medicine (Hematology/Oncology), University of Virginia,
Charlottesville, VA, USA. --
*Correspondence:
Nader Pouratian, Email: np5k@virginia.edu, Phone: 434-982-3244,
Fax: 434-243-2954.-- Received: 1 September 2006 Accepted:
2 October 2006 Published online: 3 November 2006
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Protracted low dose temozolomide (75 mg/m2/day
on days 1–21 of 28 days) offers potential advantages over
standard temozolomide schedules (200 mg/m2/day on days
1–5 of 28 days) including greater cumulative drug exposure and
depletion of O6-alkylguanine DNA alkyltransferase levels,
theoretically overcoming intrinsic chemoresistance.
We retrospectively review our experience
in 25 patients with pathologically proven low grade gliomas (LGG)
treated with protracted low dose temozolomide to primarily quantify
its toxicity and secondarily to assess efficacy.
None had previously received
radiation.
Tumor response was graded based on changes
in tumor size, steroid requirements, and clinical exam.
About 243 cycles of protracted low dose
temozolomide were administered.
Three patients (12%) were changed to
standard temozolomide dosing due to side effects, including
intractable nausea (n = 2) and multiple cytopenias (n = 1).
The most frequent toxicities were fatigue
(76%), lymphopenia (72% [48% high grade]), constipation (56%), and
nausea (52%).
High grade toxicities (other than
lymphopenia) included secondary malignancy, pruritis, hyponatremia,
neutropenia, leukopenia, and cognitive decline (n = 1
for each).
Tumor response rate was 52% and and
disease control rate was 84%.
Six month PFS was 92% and 12 month
PFS was 72%.
Response rates and PFS were independent of
pathological subtype, deletion status, and indication for
chemotherapy.
Protracted low dose temozolomide has a
distinct spectrum of toxicities compared to standard dosing but is
well tolerated in most patients and may provide improved response
rates compared to standard dosing.
The results of larger randomized trials
are needed to assess its potential advantages over other management
schemes.
Keywords: Chemotherapy, Glioma, Low
grade glioma, Temozolomide, Toxicity
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© 2006 Springer
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