Abstract
Gynecologic cancers represent a significant problem worldwide. Advanced, recurrent gynecologic cancers are often refractory to chemo-therapy, so new treatment regimens are needed. Pemetrexed is a third-generation, multi-targeted antifolate that has been approved for use in non-squamous non-small cell lung cancer and malignant pleural mesothelioma in both the United States and European Union. This paper reviews the safety and efficacy of pemetrexed in gynecologic cancers, which were defined as maligancies of the ovaries (including fallopian tubes and primary peritoneum), uterine endometrium, and uterine cervix. A search of English-language literature via PubMed and American Society of Clinical Oncology proceedings was performed from database inception to June 2012. Thirteen clinical trials involving the use of pemetrexed (alone and in combination with other agents) in gynecologic cancers were identified. These were phase I and phase II trials; there were 9 studies in ovarian cancer, 1 study in endometrial cancer, and 3 studies in cervical cancer. Pemetrexed with vitamin supplementation was tolerable in all clinical trials and had activity in ovarian and cervical cancers. Therefore, it may be reasonable to further explore the use of pemetrexed in ovarian and cervical malignancies.
Highlights
Antimetabolites act by disrupting cell replication and division [1]
English-language literature was identified through searches of PubMed and Proceedings of the American Society of Clinical Oncology (ASCO)
In 2012, an estimated 22,280 new cases of ovarian cancer are expected in the United States (US), with an estimated 15,500 deaths
Summary
Antimetabolites act by disrupting cell replication and division [1]. This disruption can occur directly through incorporation of analogues into cellular DNA or indirectly through interference with pathways involved in DNA synthesis. Eukaryotic cells require folates, which transfer 1-carbon units needed for the biosynthesis of pyrimidines, purines, and some amino acids, for growth [2,3]. Diet-derived folic acid must be reduced to tetrahydrofolate (THF), which serves as the 1-carbon (methyl group) donor in biosynthetic processes. Deletion of intracellular THF co-factors inhibits the biosynthesis of purine nucleotides and thymidine, thereby inhibiting DNA synthesis [4]. Antifolates have the greatest effect on rapidly growing and dividing cells, and affect rapidly growing normal cells, such as those in bone marrow and the gastrointestinal tract, thereby explaining toxicities of this compound class [5]
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