Basic and Clinical Research for Treatment of Malignant Ovarian Tumor

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Ovarian carcinoma presents many difficulties in treatment because of the advanced stage and drug resistance. We organized Tokai ovarian tumor study group and registered patients were treated with CAP (cyclophosphamide, adriamycin, cisplatin) or PVB (cisplatin, vinblastin, bleomycin) randomly. Forty-seven of 181 cases had no clinical remission and 86% of them died within 20 months after primary surgery. Fifty-four cases had no recurrence and a subsequent recurrence. Independent remission factors by multivariate analysis were higher stage, clear cell carcinoma, larger maximum residual tumor, and PVB therapy. A significantly high remission rate and low recurrence rate was achieved using PVB therapy. The disease-free survival after clinical remission was the same as that after a negative second-look laparotomy, which implies that a second-look laparotomy may be unnecessary in the management of ovarian carcinoma. Complete resection of tumor with lymphadnectomy tended to increase disease-free survival compared to that without lymphadnectomy in the second operation as well as the first. Now, a randomized trial comparing CAP or PP (cisplatin, carboplatin) is under way.Several possive mechanism of the resistance to cisplatin are proposed. NOS2CR cells show 7.0 times resistance to cisplatin compared to parental cells (NOS2) derived from serous cystadenocarcinoma of the ovary. Decreased intracellular cisplatin content and increased activity of GST are the main mechanisms in NOS2CR.Amphotericin B (AMB) can potentiate the cytotoxicity of anticancerdrugs, such as adriamycin and mitomycin C.The enhancing effect of AMB on cisplatin was examined. AMB sensitized NOS2CR as well as NOS2 to cisplatin, partially due to the increasing intracellular accumulation of cisplatin. Furthermore, intraperitoneal administration of AMB and cisplatin produced an increase in survival time in tumor-bearing nude mice compared to cisplatin alone.