[Treatments of epithelial ovarian cancer by histologic subtype]

Recent molecular studies support the hypothesis that clear cell carcinoma and mucinous adenocarcinoma are refractory cancers that are biologically distinct from serous adenocarcinoma. Treatment of these cancers has not yet been adequately tested, so separate clinical trials are needed for each type. Paclitaxel(175 mg/m2/3hr)combined with carboplatin AUC 6(TC regimen)is the current gold standard for treating ovarian cancer. Clear cell carcinoma and mucinous adenocarcinoma are less sensitive to a TC regimen than serous adenocarcinoma, and an international randomized trial for clear cell carcinoma is now underway(GCIG/JGOG3017). Targeted therapy is attractive for chemoresistant clear cell carcinoma, thus VEGFR inhibitor(sunitinib), PDGFR inhibitor(sorafenib), m-TOR inhibitor (temsirolimus), and monoclonal antibody(bevacizumab)are being evaluated. Mucinous adenocarcinoma often shows CK20- and CEA-positive patterns in immunohistochemistry, and furthermore, p53-negative and K-ras-positive in molecular markers, which suggests that mucinous adenocarcinoma resembles colorectal, stomach, and pancreas cancers more than serous ovarian adenocarcinoma. Trials are needed to test the agents effective for gastrointestinal cancer. The GOG will start a randomized phase III trial comparing TC regimen with capecitabine plus oxaliplatin(GOG241). We are starting a phase II study of S-1 plus oxaliplatin in Japan. For refractory cancers, molecular biology-based, cross- organ treatment with cytotoxic/cytostatic agents is needed.