Endometrial cancer (EC) is the 8th most common female cancer in Taiwan. Its incidence is
increasing in the recent few years, around 1,200 new cases per year. The outcome of recurrent
EC is disappointing, except focal recurrences that could be irradiated or removed.
Chemotherapy is currently the most common salvage treatment for recurrent endometrial cancer.
However, the response rate (RR) to 2nd-line treatment is approximately 0-27.3%, with short
median time to progression, 2-3.9 months and low overall survival, 6.4-11 months.
Due to progress of studies on the molecular and genetic basis of cancer and cellular
signaling pathways, targeted therapy has been developed for various cancer treatments. A
Gynecologic Oncology Group study found 44% of advanced endometrial cancer had HER>=2+ and the
ratio of HER2:chromosome 17 (CEP17) >=2. Another study showed that HER>=2+ was seen in 47% of
carcinosarcoma. These evidences indicated HER2 gene amplification and HER2 overexpression
occur in endometrial cancer and carcinosarcoma, especially in those of high grade and
recurrence. Lapatinib (L), an oral inhibitor of both EGFR(epidermal growth factor receptor)
and HER2(human epidermal growth receptor), has been shown to be an effective treatment in
HER2/neu overexpressing metastatic breast cancer. Ixabepilone is a semisynthetic analog of
the natural product epothilone B, and recently has been approved by US Food and Drug
Administration as a treatment option in metastatic breast cancer. It was also observed that
lapatinib + ixabepilone killed more breast tumor cells than trastuzumab + paclitaxel in
vitro. Two GOG(Gynecologic Oncology Group) studies had reported that weekly Ixabepilone as
2nd-line chemotherapy provided a similar RR to 3-weekly regimen of 14.3% in platinum- and
taxane-resistant epithelial ovarian cancer with less severe toxicities. The combination of
lapatinib and ixabepilone is expected to become an effective treatment for recurrent
endometrial cancer and carcinosarcoma, but the ideal dose is yet to be surveyed.