Temozolomide in advanced and recurrent uterine leiomyosarcoma and correlation with o6-methylguanine DNA methyltransferase expression: a case series.
BACKGROUND
Our objective was to retrospectively review temozolomide in advanced and recurrent uterine leiomyosarcoma and to determine if tumor O-methylguanine DNA methyltransferase (MGMT) expression correlated with clinical response.


METHODS
All patients with advanced or recurrent uterine leiomyosarcoma who received temozolomide during treatment were retrospectively identified. Relevant clinical and pathologic data were collected and compared. O-Methylguanine DNA methyltransferase expression was assessed by immunohistochemistry and scored by a gynecologic pathologist blinded to clinical outcomes.


RESULTS
From 1999 to 2008, 9 cases of leiomyosarcoma were diagnosed; 6 patients received temozolomide. Median follow-up was 54 months (range, 4-114 months). There was 1 patient with complete response, 1 durable partial response (27+ months), 3 stable disease (range, 3-10 months), and 1 progressive disease. Overall, 5 out of 6 patients derived clinical benefit. The patient with a complete response recurred 18 months after her last cycle. Median progression free interval was 15.4 months (95% confidence interval, 9.4-21.4). Two patients died of disease. Temozolomide was well tolerated with no dose-limiting toxicities, and no dose adjustments were required in 64 prescribed cycles. The MGMT expression was inversely correlated with response to temozolomide. Patients with tumors negative for MGMT expression had a median progression free interval of 18.5 months compared with 3 months for those whose tumors were positive, although not statistically significant.


CONCLUSIONS
Temozolomide is an easily administered, well-tolerated chemotherapeutic option in advanced or recurrent uterine leiomyosarcomas with a reasonable response rate. Assessment of MGMT expression may identify a subset of patients that will respond optimally to this therapy.
Department of Obstetrics and Gynecology, University of Virginia Health System, PO Box 800712, Charlottesville, VA 22908, USA. jsf8w@virginia.edu
J Stuart
JS
Ferriss
Kristen A
KA
Atkins
Jason A
JA
Lachance
Susan C
SC
Modesitt
Amir A
AA
Jazaeri
D000328:Adult; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D054316:Biomarkers, Pharmacological / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007890:Leiomyosarcoma / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism / Q000601:surgery; D008875:Middle Aged; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000378:metabolism*; D011379:Prognosis; D012008:Recurrence; D012189:Retrospective Studies; D000077204:Temozolomide; D014594:Uterine Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism / Q000601:surgery
D018906:Antineoplastic Agents, Alkylating; D054316:Biomarkers, Pharmacological; D014408:Biomarkers, Tumor; D003606:Dacarbazine; D019853:O(6)-Methylguanine-DNA Methyltransferase; D000077204:Temozolomide