Imatinib mesylate and its potential implications for gynecologic cancers.
Among gynecologic malignancies, ovarian carcinoma is the most frequent cause of death, with the majority of patients presenting at advanced stage. There is a high rate of recurrence despite first-line chemotherapy. Sarcoma of the uterus, while accounting for a small percent of uterine cancers, is also associated with a high-recurrence rate and poor overall survival. Therefore, the development of novel treatment strategies is paramount. Imatinib mesylate (Gleevec; Novartis Pharmaceuticals Corp., East Hanover, NJ) is a tyrosine kinase inhibitor with activity against abl, c-kit, and platelet derived growth factor receptor (PDGFR), and is approved for the treatment of chronic myelogenous leukemia and gastrointestinal stromal tumor. Preclinical data provides evidence for c-kit and PDGFR expression in ovarian epithelial carcinomas and uterine sarcomas and have led to clinical trials evaluating the use of imatinib in these malignancies. Additionally, inhibition of PDGFR signaling has been proposed as an effective mechanism of chemotherapy by lowering tumor interstitial fluid pressure. Recent data have also suggested benefit with metronomic scheduling of cytotoxic agents at lower doses at more frequent dosing intervals, in combination with other targeted therapies. While activity of this agent remains to be established, further studies of imatinib in gynecologic malignancies are warranted, to demonstrate not only single-agent activity and the enhancement of cytotoxicity of other antineoplastic agents.
Dushkin
Holly
H
Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA.
Schilder
Russell J
RJ
D001549:Benzamides; D001682:Biological Availability; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005833:Genital Neoplasms, Female / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D006801:Humans; D000068877:Imatinib Mesylate; D020714:Maximum Tolerated Dose; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control*; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D010879:Piperazines / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011379:Prognosis; D011743:Pyrimidines / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018570:Risk Assessment; D016019:Survival Analysis; D016896:Treatment Outcome; D014594:Uterine Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology
D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate
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