CD70 antibody-drug conjugate: A potential novel therapeutic agent for ovarian cancer.

This study aimed to investigate the cytotoxicity of a cluster of differentiation 70 antibody-drug conjugate (CD70-ADC) against ovarian cancer in in vitro and in vivo xenograft models. CD70 expression was assessed in clinical samples by immunohistochemical analysis. Western blotting and fluorescence-activated cell sorting analyses were used to determine CD70 expression in the ovarian cancer cell lines A2780 and SKOV3, and in the cisplatin-resistant ovarian cancer cell lines A2780cisR and SKOV3cisR. CD70 expression after cisplatin exposure was determined in A2780 cells transfected with mock- or nuclear factor (NF)-κB-p65-small interfering RNA. We developed an ADC with an anti-CD70 monoclonal antibody linked to monomethyl auristatin F and investigated its cytotoxic effect. We examined 63 ovarian cancer clinical samples; 43 (68.3%) of them expressed CD70. Among patients with advanced stage disease (n = 50), those who received neoadjuvant chemotherapy were more likely to exhibit high CD70 expression compared to those who did not (55.6% [15/27] vs 17.4% [4/23], P < .01). CD70 expression was confirmed in A2780cisR, SKOV3, and SKOV3cisR cells. Notably, CD70 expression was induced after cisplatin treatment in A2780 mock cells but not in A2780-NF-κB-p65-silenced cells. CD70-ADC was cytotoxic to A2780cisR, SKOV3, and SKOV3cisR cells, with IC50 values ranging from 0.104 to 0.341 nmol/L. In A2780cisR and SKOV3cisR xenograft models, tumor growth in CD70-ADC treated mice was significantly inhibited compared to that in the control-ADC treated mice (A2780cisR: 32.0 vs 1639.0 mm3 , P < .01; SKOV3cisR: 232.2 vs 584.9 mm3 , P < .01). Platinum treatment induced CD70 expression in ovarian cancer cells. CD70-ADC may have potential therapeutic implications in the treatment of CD70 expressing ovarian cancer.

[Comparison between Primary Debulking Surgery and Neo-Adjuvant Chemotherapy Followed by Interval Debulking Surgery for Patients with Stage III-IV Ovarian Cancer].

The current standard treatment for advanced ovarian cancer is primary debulking surgery(PDS). We may expect a good prognosis if complete debulking(no visible residual tumor)is possible. However, if complete surgery is not possible owing to the location of the tumor or poor performance status, neo-adjuvant chemotherapy(NAC)could be an alternative option. Interval debulking surgery(IDS)can be planned after NAC to try and achieve complete debulking surgery. We reviewed stage III and IV epithelial ovarian cancers treated at Kansai Rosai Hospital between January 2012 and January 2016. Fifty-one cases (PDS: 22 cases, NAC-IDS: 29 cases)were enrolled in our analysis. Progression-free survival(PFS), overall survival(OS), the successful complete surgery rate, and the contents and complications of the surgery were compared between the PDS and NAC-IDS groups. There was no significant difference in PFS and OS between the 2 groups(PFS: p=0.467, OS: p=0.685). Blood loss was larger in the PDS group(p=0.013). Patients in the NAC-IDS group were likely to be able to eventually achieve complete surgery(p=0.016). NAC followed by IDS is one of the effective treatment options for advanced ovarian cancers.

[A Retrospective Analysis of Systematic Lymphadenectomy for Loco-Regional(pT1)Epithelial Ovarian Cancer].

BACKGROUND: The incidence of lymph node metastasis in pT1 epithelial ovarian cancer is between 5% and 21%. Most cases with lymph node metastasis are those of serous carcinoma; it is relatively rare in mucinous carcinoma. Therefore, there is a recent trend to omit systematic lymphadenectomy in early stage mucinous carcinoma. The purpose of this study was to verify whether the omission of systematic lymphadenectomy in mucinous carcinoma is oncologically safe. METHODS: We reviewed all pT1 epithelial ovarian cancer cases that were treated in our hospital between January 2002 and December 2015. RESULTS: Fiftynine cases of pT1 epithelial ovarian cancer were included. The overall rate of lymph node metastasis was 6.8%(4 in 59). It was 6.5%(2 in 31)in clear cell carcinoma and 22.2%(2 in 9)in mucinous carcinoma. CONCLUSION: According to our study, lymph node metastasis in pT1 mucinous carcinoma has a rate of 22.2% and some affected cases were not detected by presurgery imaging studies. Therefore, we need to be careful about the omission of systematic lymphadenectomy in mucinous carcinoma.

[A Retrospective Case Study of Combination Chemotherapy with Bevacizumab for Recurrent Ovarian Cancer].

OBJECTIVES: Treatment for ovarian cancer with bevacizumab(Bmab)has been covered by public medical insurance in Japan since November 2013. It is recommended that the use of Bmab is limited to the first treatment for FIGO stage III or IV ovarian cancer. The OCEAN trial for platinum sensitivity in relapsed patients and the AURELIA trial for platinum-resistance in relapsed patients were performed, and both significantly improved progression-free survival. METHOD: We retrospectively studied patients receiving Bmab with an anticancer agent for recurrent ovarian cancer. Written informed consent was obtained from all patients. RESULTS: Between November 2013 and September 2015, Bmab at 15mg/kg/3-4 week was administered to 20 patients with recurrent ovarian cancer. The median age was 58 years(range 32-81)and the median performance status was 0-2. Platinum-sensitive recurrence occurred in 6 patients. The response rate and disease control rate of combination chemotherapy with Bmab was 50.0% and 57.1%. However, 11 patients stopped treatment with Bmab due to serious adverse events. CONCLUSION: Combination chemotherapy with Bmab for recurrent ovarian cancer may be feasible.