Hiroko Kouta

Effects of bevacizumab and pegylated liposomal doxorubicin for the patients with recurrent or refractory ovarian cancers.

OBJECTIVES Currently, pegylated liposomal doxorubicin (PLD) is regarded as one of the standard treatment options in recurrent ovarian cancers (ROC). Bevacizumab has shown significant antitumor activity for ROC in single-agent or in combination with cytotoxic agents. We have conducted a preliminary study to investigate effects of combination of bevacizumab and PLD for heavily pretreated patients with ROC. METHODS Thirty patients with ROC were treated with combination therapy with weekly bevacizumab and PLD, 2 mg/kg of continuous weekly bevacizumab and 10 mg/m(2) of PLD (3 weeks on, 1 week off). The treatment was continued until development of disease progression, or unmanageable adverse effects. Response evaluation was based upon Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0, and Gynecologic Cancer Intergroup (GCIG) CA125 response criteria. Adverse effects were analyzed according to Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. RESULTS Overall response rate was 33%, and clinical benefit rate (CR+PD+SD) was 73%. Median progression-free survival was 6 months (range: 2-20 months), and a 6-months progression-free survival was 47%. Any hematological toxicities more than grade 3 were not observed. Two cases developed non-hematologic toxicities more than grade 2; a case with grade 3 hand-foot syndrome, another with grade 3 gastrointestinal perforation (GIP). The case with GIP was conservatively treated and recovered after 2 months, and there was no case with treatment-related death. CONCLUSION The present investigation suggested that combination therapy with bevacizumab and PLD was active and well tolerated for patients with ROC. We recommend the regimen be evaluated in further clinical studies.

Weekly administration of bevacizumab, gemcitabine, and oxaliplatin in patients with recurrent and refractory ovarian cancer: a preliminary result of 19 cases.

Objective Combination therapy using gemcitabine with oxaliplatin (GEMOX) showed moderate activity in recurrent ovarian cancers. However, severe toxicities have been observed in patients who received full-dose therapy of GEMOX. On the other hand, bevacizumab enhances chemotherapeutic efficacy in various cancers. Here, we evaluated the effect of weekly low-dose administration of GEMOX in combination with bevacizumab (B-GEMOX) for patients with recurrent and refractory ovarian cancers (ROCs). Methods A total of 19 patients with ROC were treated with B-GEMOX: 2 mg/kg of bevacizumab, 300 mg/m2 of gemcitabine, and 30 mg/m2 of oxaliplatin, 3 weeks on and 1 week off, q4weeks. The treatment was continued until development of severe toxicities or progressive disease. Tumor responses were assessed using the Response Evaluation Criteria in Solid Tumors and Gynecologic Cancer Intergroup criteria. Results Median number of the B-GEMOX therapy was 5 cycles. Response was observed in 4 (34%) cases by Response Evaluation Criteria in Solid Tumors, and in 2 (29%) cases by Gynecologic Cancer Intergroup criteria, resulting in overall response rate of 32%. Clinical benefit excluding progressive disease was obtained in 79% of the patients. Median progression-free survival was 4.5 months (range, 2–16+ months). Toxicities were mild and mainly consisted of hematologic, gastrointestinal, and neuropathy; however, there were no nonhematologic toxicities more than grade 1. Conclusions Weekly administration of B-GEMOX was active for patients with ROC and showed mild toxicities. These results warrant further prospective studies for patients with ROC.

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.