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A phase I trial of
temozolomide and vinorelbine in patients with recurrent brain metastases
A. M. P. Omuro, J. J. Raizer, L. E. Abrey
Memorial Sloan-Kettering Cancer Center, New York, NY
Background. The prognosis of recurrent brain metastasis (BM) is
poor.
We designed a Phase I trial combining temozolomide (TMZ), an agent with efficacy
in BM, with vinorelbine, a lipophilic agent with activity against a variety of
solid tumors, to establish the maximum tolerated dose (MTD) of vinorelbine for
this combination.
Methods.
Patients with solid tumors and
recurrent or progressive BM were eligible.
Chemotherapy consisted of 28 day cycles with TMZ (150 mg/m2 on days 1
to 7 and 15 to 21) and vinorelbine (days 1 and 8 at escalating doses).
The starting dose was 15 mg/m2, with increments of 5 mg/m2
for each cohort of 3 patients, until MTD was reached.
Results. 14 pts enrolled (5 men); median
age was 59 (41-76) years; median KPS was 80 (70-100).
Seven pts had non-small cell lung CA, 3 small-cell lung cancer, 3 breast and 1
renal cell.
Vinorelbine dose/m2 was 15mg in 7, 20mg in 4 and 25mg in 3.
Six patients were taken off study for disease progression, 3 for toxicity, 3 for
withdrawal of consent, 1 for clinical deterioration and 1 for
non-compliance.
The median time to progression was 3 (1-7) months.
Of the 10 that completed at least one cycle, 1 achieved a minor response, 3
stable disease and 6 progressed (5 in the brain, 1 systemically).
Median overall survival was 7.5 (2-13) months.
Grades 3/ 4 neutropenia in 4 patients and thrombocytopenia in 5 were the only
serious adverse events.
Conclusions. To date this regimen has
been well tolerated and a phase II study is warranted to define efficacy.
Copyright 2004 American Society of Clinical Oncology All rights
reserved worldwide.
Source: http://www.asco.org/ac/1,1003,_12-002636-00_18-0026-00_19-00856,00.asp
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