Short response duration even in responders to chemotherapy using conventional cytotoxic agents in recurrent or refractory clear cell carcinomas of the ovary

Takano, Masashi; Gotō, Tomoko; Kato, Masafumi; Sasaki, Naoki; Miyamoto, Morikazu; Furuya, Kenichi

doi:10.1007/s10147-012-0404-x

Cited by 9 publications

(8 citation statements)

References 12 publications

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“…These observations run counter to the prediction that ovarian cancers with clear cell histology would be less likely to respond to PD-1 inhibitors based on low PD-1 expression and low TIL infiltration (Table 2). However, they are particularly intriguing given the characteristic chemorefractory nature of ovarian clear cell carcinomas (OCCC) [34, 35]. Because OCCC are genomically remarkably similar to RCC, it has been postulated that therapies effective for RCC may be similarly effective for OCCC [36].…”

Section: Introductionmentioning

confidence: 99%

The role of immune checkpoint inhibition in the treatment of ovarian cancer

Gaillard

Secord

Monk

2016

gynaecol oncol res pract

127

109

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The introduction of immune checkpoint inhibitors has revolutionized treatment of multiple cancers and has bolstered interest in this treatment approach. So far, emerging clinical data show limited clinical efficacy of these agents in ovarian cancer with objective response rates of 10–15% with some durable responses. In this review, we present emerging clinical data of completed trials of immune checkpoint inhibitors and review ongoing studies. In addition we examine the current knowledge of the tumor microenvironment of ovarian cancers with a focus on the significance of PD-L1 expression and tumor-infiltrating lymphocytes on predicting response to immune checkpoint blockade. We evaluate approaches to improve treatment outcomes through the use of predictive biomarkers and patient selection. Finally, we review management considerations including immune related adverse events and response criteria.

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Section: Introductionmentioning

confidence: 99%

The role of immune checkpoint inhibition in the treatment of ovarian cancer

Gaillard

Secord

Monk

2016

gynaecol oncol res pract

127

109

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“…Particularly for recurrent OCCC, the response rate (RR) to salvage chemotherapy was extremely low 3,4 . Even in patients who achieved a response when they received conventional anticancer cytotoxic drugs, progression-free survival was less than 6 mo 5 . In addition, we previously reported approximately two in three recurrent OCCC patients died within 12 mo of recurrence 6 .…”

Section: Introductionmentioning

confidence: 99%

Efficacy of glypican-3-derived peptide vaccine therapy on the survival of patients with refractory ovarian clear cell carcinoma

et al. 2016

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Compared with other epithelial ovarian carcinoma subtypes, ovarian clear cell carcinoma (OCCC) has been recognized to show chemoresistance. Therefore, new treatment modalities are required for patients with OCCC that is refractory to chemotherapy. The carcinoembryonic antigen glypican-3 (GPC3) is expressed by approximately half of OCCC and is a promising immunotherapeutic target. The purpose of this study was to evaluate the effect of GPC3 peptide vaccine against refractory OCCC patients. We conducted a phase II trial with a GPC3-derived peptide vaccine in OCCC patients. Immunological responses were analyzed by ex vivo IFNγ ELISPOT assay. We also evaluated control subjects, who received best supportive care without vaccinations during the same period.Thirty-two patients with refractory OCCC were enrolled between July 2010 and September 2015, and underwent GPC3 peptide vaccination. Fifteen patients were vaccinated less than six times because their general condition progressively deteriorated, and 17 patients were vaccinated at least six times. Three patients showed a partial response as the best overall response. The GPC3 peptide vaccine induced a GPC3-specific CTL response in 15 out of 24 patients who had PBMCs collected three times or more. The prognosis of palliative care patients without GPC3 peptide vaccinations was significantly poorer than that of those with GPC3 peptide vaccinations (post cancer-treatment survival: p = 0.002).Although the disease control rate was not high, our results suggest that GPC3 peptide vaccinations may hold a significant impact to prolong survival of patients with refractory OCCC, allowing them to maintain quality of life with no serious toxicities.

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“…First, CCC showed chemoresistance to primary chemotherapy using platinum-based therapy and combination with paclitaxel and platinum (Takano et al , 2012). Lower response was also reported in the second-line chemotherapy (Takano et al , 2008), and response duration was extremely short (Takano et al , 2013). Second, CCC had significantly worse overall survival (OS) in advanced-staged tumours (Sugiyama et al , 2000; Winter et al , 2007).…”

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confidence: 99%

X-chromosome-linked inhibitor of apoptosis as a key factor for chemoresistance in clear cell carcinoma of the ovary

et al. 2014

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Background:X-chromosome-linked inhibitor of apoptosis (XIAP) is one of the anti-apoptotic proteins leading to chemoresistance in several cancers. The aim of this study is to evaluate the impact of XIAP expression upon ovarian clear cell carcinoma (CCC) that has a platinum-resistant phenotype.Methods:Tissue microarrays made from 90 CCC patients were analysed for immunohistochemical expression levels of XIAP, c-Met, p-Akt and Bcl-XL. In addition, CCC cell lines were evaluated whether XIAP silencing could modulate sensitivity to platinum agent in vitro.Results:High XIAP expression was observed in 30 (33%) of 90 CCC cases, and was associated with c-Met (<0.01) and Bcl-XL (<0.01) expression. Cases with high XIAP expression had lower response rate to primary platinum-based chemotherapy (10% vs 65%, P=0.02). In stages II–IV tumours, high XIAP expression was related with worse progression-free survival (PFS, P=0.02). Furthermore, high XIAP expression was identified as an independent worse prognostic factor for PFS and overall survival. Finally, downregulation of XIAP using XIAP-specific small interfering RNA increased sensitivity to cisplatin in human cancer cells derived from CCC.Conclusions:X-chromosome-linked inhibitor of apoptosis expression was correlated with chemoresistance of primary chemotherapy, and identified as a prognostic marker for CCC. X-chromosome-linked inhibitor of apoptosis could be a candidate for new therapeutic target in CCC.

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Short response duration even in responders to chemotherapy using conventional cytotoxic agents in recurrent or refractory clear cell carcinomas of the ovary

Cited by 9 publications

References 12 publications

The role of immune checkpoint inhibition in the treatment of ovarian cancer

The role of immune checkpoint inhibition in the treatment of ovarian cancer

Efficacy of glypican-3-derived peptide vaccine therapy on the survival of patients with refractory ovarian clear cell carcinoma

X-chromosome-linked inhibitor of apoptosis as a key factor for chemoresistance in clear cell carcinoma of the ovary

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