ACTIVITY OF CYTOTOXIC AGENTS AGAINST CLEAR-CELL CARCINOMA OF THE OVARY WHICH IS INTRINSICALLY PLATINUM-REFRACTORY

The aim of the present study was to evaluate cytotoxic agents active f or clear cell carcinoma of the ovary (OCCA) which is intrinsically pla tinum-resistant. We first conducted in vitro chemosensitivity tests as sessing antitumor activities of Various agents against OCCA using two cell lines (HAC-2 and KK) established from ascites of patients with pu re OCCA. The most potent single agent was SN-38 (active substance of C PT-11 in vivo) in both cell lines. The second most potent agent was mi tomycin-C (MMC) followed by doxorubicin (DOX) in HAC-2 and DOX followe d by MMC in KK, respectively. In vivo chemosensitivity test of agents on HAC-2 transplanted into BALB/C nude mice demonstrated that MMC was most potent, followed by DOX and CPT-11. Moreover, a combination of CP T-11 and MMC exhibited the highest anti-tumor activity in this animal model. Cisplatin, etoposide, and paclitaxel were found to be ineffecti ve in either the in vitro or in vivo experimental system. Clinical tri al with a combination of MMC and CPT-11 are warranted in patients with OCCA.