Masashi Takano, Hiroko Kouta, Naoki Sasaki, Kazuya Kudoh, Tsunekazu Kita, Ryoko Kikuchi, Katsutoshi Oda, Tomoko Goto, Kenichi Furuya, Yoshihiro Kikuchi; Ohki Memorial Kikuchi Cancer Center for Women, Tokorozawa, Japan; National Defense Medical College, Tokorozawa, Japan; National Hospital Organization, Nishisaitama Chuo Hospital, Tokorozawa, Japan; Nara Prefectural Nara Hospital, Nara, Japan; Department of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan .Background: Clear cell carcinoma (CCC) of the ovary showed exceedingly chemo-resistant phenotype, especially in the case with recurrent or refractory to previous therapy. An inhibitor against the mammalian target of rapamycin (mTOR), temsirolimus, has been reported to be effective in renal CCC. Additionally, a marine natural product, trabectedin, had activity against recurrent ovarian cancers. We evaluated the effect of combination therapy with temsirolimus and trabectedin for patients with recurrent/refractory CCC of the ovary.
Methods: Patients with recurrent/refractory CCC of the ovary were treated with weekly regimen using two drugs: 10mg/m2 of temsirolimus and 0.15mg/m2 of trabectedin (3 weeks, one week rest) with written informed consents.
Treatment was continued until development of progressive disease (PD) or unmanageable adverse effects. Responses were evaluated by RECIST criteria, and adverse effects were analyzed by NCI-CTCAE v4.0. Results: A total of 12 patients treated with the regimen, and there were no cases that discontinued the therapy due to toxicities. Median age was 60 years (range: 42-69), and median number of previous chemotherapy was 3 (range: 1-5). All cases were assessable by RECIST and CTCAE. One patient (8%) had a complete response (CR), and another (8%) achieved a partial response (PR), and 4 patients (33%) had stable disease (SD) beyond three months, resulting in clinical benefit rate (CBR; CR+PR+SD>3month) of 50%. Median response duration in CBR case was 3.5 months (range: 3-12+). There were no cases that developed toxicities more than grade2.
Conclusions: The present preliminary study demonstrated combination therapy with temsirolimus and trabectedin was effective in patients with recurrent/refractory CCC of the ovary. These results warrant further study in such clinical settings.