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Temozolomide in advanced and recurrent uterine leiomyosarcoma and correlation with o6-methylguanine DNA methyltransferase expression: a case series.

AbstractINTRODUCTION:
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.
AuthorsJ Stuart Ferriss, Kristen A Atkins, Jason A Lachance, Susan C Modesitt, Amir A Jazaeri
JournalInternational journal of gynecological cancer : official journal of the International Gynecological Cancer Society (Int J Gynecol Cancer) Vol. 20 Issue 1 Pg. 120-5 (Jan 2010) ISSN: 1525-1438 [Electronic] England
PMID20130512 (Publication Type: Evaluation Study, Journal Article)
Chemical References
  • Antineoplastic Agents, Alkylating
  • Biomarkers, Pharmacological
  • Biomarkers, Tumor
  • Dacarbazine
  • O(6)-Methylguanine-DNA Methyltransferase
  • Temozolomide
Topics
  • Adult
  • Antineoplastic Agents, Alkylating (therapeutic use)
  • Biomarkers, Pharmacological (metabolism)
  • Biomarkers, Tumor (metabolism)
  • Dacarbazine (analogs & derivatives, therapeutic use)
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Humans
  • Leiomyosarcoma (diagnosis, drug therapy, metabolism, surgery)
  • Middle Aged
  • O(6)-Methylguanine-DNA Methyltransferase (metabolism)
  • Prognosis
  • Recurrence
  • Retrospective Studies
  • Temozolomide
  • Uterine Neoplasms (diagnosis, drug therapy, metabolism, surgery)

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