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Temozolomide in Advanced and Recurrent Uterine Leiomyosarcoma and Correlation With O6-Methylguanine DNA Methyltransferase Expression: A Case Series
  1. J. Stuart Ferriss, MD*,
  2. Kristen A. Atkins, MD,
  3. Jason A. Lachance, MD*,
  4. Susan C. Modesitt, MD* and
  5. Amir A. Jazaeri, MD*
  1. *Thornton Gynecologic Oncology Service, and
  2. Department of Pathology, University of Virginia Health System, Charlottesville, VA.
  1. Address correspondence and reprint requests to J. Stuart Ferriss, Department of Obstetrics and Gynecology, University of Virginia Health System, PO Box 800712, Charlottesville, VA 22908. E-mail: jsf8w{at}virginia.edu.

Abstract

Introduction: Our objective was to retrospectively review temozolomide in advanced and recurrent uterine leiomyosarcoma and to determine if tumor O6-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. O6-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.

  • Uterine leiomyosarcoma
  • Temozolomide
  • MGMT

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Footnotes

  • Authorship statement: All authors have directly participated in the planning, execution, or analysis of this study, and they have approved the final manuscript.

  • Conflict of interest statement: All authors indicate there are no conflicts of interest to declare.

  • Jason A. Lachance is currently with the Maine Medical Partners, 102 Campus Dr, Scarborough, ME 04074.

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