Kazuya Kudoh

Abstract LB-226: The effect of cabozantinib to temozolomide and bevacizumab in patients with heavily pretreated relapsed uterine leiomyosarcoma

Background: Although uterine leiomyosarcoma (ULMS) has been treated with adriamycin, dacarbazine, ifosfamide, gemcitabine, docetaxel, et al, the effect is not satisfactory. We have reported the effect of temozolomide (T) combined with bevacizumab (B) in heavily pretreated relapsed ULMS. In this study, we evaluated the effects of addition of cabozantinib (C) to T and B. Methods: From 2009 to 2015, total 18 patients (pts) with heavily pretreated relapsed ULMS were enrolled. They were treated with T (80mg/body/day) and B (2mg/kg; days 1, 8 and 15, q4 weeks). Since 2013, we expected better efficacy, nine pts out of 18 pts were treated by adding C (140mg/body/week) which is a c-MET inhibitor (TB, n = 9, CTB, n = 9). Treatment was continued until disease progression and/or unmanageable toxicities. The response and adverse events were evaluated using the response evaluation criteria in solid tumors (RECIST), and common terminology criteria for adverse events (CTCAE) version 3.0. Results: As shown in Table, three (18%) of 17 pts had complete response (CR), two (12%) had partial response (PR) and eight (47%) had stable disease (SD) for at least three months. The response rate (RR; CR+PR) and clinical benefit rate (CBR; CR+PR+SD>3mo) were 29% and 76%, respectively. The median progression-free survival was 9.6 (3 - 58) months. When compared CTB with TB, CBR was better in CTB (87.5% vs 67%), but the median administration cycles and progression free interval were not improved. Two peritoneal perforation were observed in CTB. Conclusions: Not only TB but also CTB showed remarkable effect in heavily pretreated relapsed ULMS. These results warrant further prospective and randomized studies. Citation Format: Sayaka Ikeda, Kazuya Kudoh, Naoki Sasaki, Masashi Takano, Tomoko Goto, Ryoko Kikuchi, Tsunekazu Kita, Masaru Sakamoto, Nobuyuki Susumu, Daisuke Aoki, Hiroko Kouta, Yoshihiro Kikuchi. The effect of cabozantinib to temozolomide and bevacizumab in patients with heavily pretreated relapsed uterine leiomyosarcoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-226.

UGT1A1 genotype-based phase I study for recurrent and refractory gynecologic cancer patients treated with combination therapy of irinotecan and cisplatin (STB-06).

e15503 Background: In addition to polymorphisms of UGT1A1*28, UGT1A1*6 has been recognized as a risk factor for severe irinotecal-related toxicities. We have conducted an UGT1A1 genotype-based dose-escalation study for recurrent and refractory gynecologic cancer patients (pts) treated with combination with irinotecan and cisplatin (CPT-P). METHODS Pts eligible for this study had histologically confirmed uterine cancer or ovarian cancers, who receive CPT-P; a course of therapy consisting of 30-80 mg/m2 of irinotecan on days 1, 8, and 15 and 60 mg/m2 of cisplatin on day 1, q4weeks. According to UGT1A1*28, *6, and *27 polymorphysms, pts were categorized into three groups (wild-type, hetoro-type, homo-type), and three-case cohort study was conducted. Pharmacokinetics of CPT-11, SN-38, SN-38 glucuronide (SN-38G), and platinums were also analyzed. RESULTS During August 2008 and December 2010, 19 pts were enrolled in this study; 14 ovarian cancers and 5 uterine cancers. Genotypes of UGT1A1 were wild in 7 pts, *28 in 4 pts, *6 in 5 pts, *6/*6 in 2 pts, and *6/*28 in 1pt. Recommended dose of irinotecan was determined as 50mg/m2 for wild-type patients, 40mg/m2 for hetero-type patients, and 30mg/m2 for homo-type patients, respectively. Pharmacokinetic analyses revealed both hetero-type and homo-type patients were associated with lower area under time-concentartion curve (AUC) SN-38G to SN-38 (AUCSN-38G/AUCSN-38) compared with wild-type cases, however, there was no significant difference of AUCSN-38 at the recommended dose. CONCLUSIONS The recommended doses of irinotacan for phase II CPT-P regimen according to UGT1A1*28 and *6 genotyping were determined. The results and pharmacokinetic analyses suggested the need of individualized dose of irinotecan, even at a lower dose of the drug.

Secondary cytoreductive surgery for recurrent mullerian adenocarcinomas: A comparison of serous and non-serous subtypes.

e15544 Background: The aim of the study was to evaluate the effects of secondary cytoreductive surgery on survival in patients with recurrent epithelial ovarian, tubal, and peritoneal cancer. Metho...