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Systemic therapy for non-serous ovarian carcinoma.
Chávarri-Guerra, Y, González-Ochoa, E, De-la-Mora-Molina, H, Soto-Perez-de-Celis, E
Chinese clinical oncology. 2020;(4):52
Abstract
Ovarian cancer is one of the top ten most common cancers in women around the world, with high-grade serous epithelial cancer being the most frequent type. However, around a quarter of cases consist of non-serous epithelial ovarian cancer (EOC), which is a heterogeneous group of malignancies that includes endometroid, mucinous, clear cell carcinoma (CCC), and carcinosarcoma. Another relevant group of nonepithelial tumors are those arising from germ cells or sex-cord stromal cells, which account for about 10% of all ovarian cancers. Although there are similarities in the presentation, evaluation, and management of these tumors, they have unique characteristics in terms of epidemiology, tumor biology, tumor marker expression, and response to treatment, warranting a different approach to each one of them. Collectively, the treatment of most of EOC include surgical cytoreduction followed by adjuvant systemic platinum-based chemotherapy. The most common chemotherapy and route of administration for systemic treatment is paclitaxel plus carboplatin given intravenously. However, the treatment of EOC has been rapidly evolving and emerging targeted therapies such as poly (adenosine diphosphate-ribose) polymerase inhibitors, immune checkpoint inhibitors, and antiangiogenic agents are also available. On the other hand, non-EOC responds well to combination chemotherapy used to treat testicular cancer (bleomycin, etoposide, cisplatin) and has a good prognosis. Frontline chemotherapeutic regimen selection differs according to histological subtype, molecular alterations, and patient characteristics. Here, we review specific characteristics of non-serous and non-EOC emphasizing the peculiarities of systemic therapy for each subtype.
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2.
Review of Immune Therapies Targeting Ovarian Cancer.
Fan, CA, Reader, J, Roque, DM
Current treatment options in oncology. 2018;(12):74
Abstract
The rise of immunotherapy is the greatest advance in oncology to occur over the last several years, but applications in gynecologic malignancies lag behind other tumors. The term "immunotherapy" envelops monoclonal antibodies as receptor mediators, including immune checkpoint inhibitors (ICPI), cancer vaccines, and adoptive immunotherapies alone or in combination with other therapeutic approaches. The purpose of this review is to summarize the status of immunotherapy trials in ovarian cancer and to specifically highlight data published in the last 1-2 years.
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Interim analysis of a phase I/IIa trial assessing E39+GM-CSF, a folate binding protein vaccine, to prevent recurrence in ovarian and endometrial cancer patients.
Jackson, DO, Byrd, K, Vreeland, TJ, Hale, DF, Herbert, GS, Greene, JM, Schneble, EJ, Berry, JS, Trappey, AF, Clifton, GT, et al
Oncotarget. 2017;(9):15912-15923
Abstract
BACKGROUND Folate binding protein(FBP) is an immunogenic protein over-expressed in endometrial(EC) and ovarian cancer(OC). We are conducting a phase I/IIa trial of E39 (GALE 301)+GM-CSF, an HLA-A2-restricted, FBP-derived peptide vaccine to prevent recurrences in disease-free EC and OC patients. This interim analysis summarizes toxicity, immunologic responses, and clinical outcomes to date. METHODS HLA-A2+ patients were vaccinated(VG), and HLA-A2- or -A2+ patients were followed as controls(CG). Six monthly intradermal inoculations of E39+250mcg GM-CSF were administered to VG. Demographic, safety, immunologic, and recurrence rate(RR) data were collected and evaluated. RESULTS This trial enrolled 51 patients; 29 in the VG and 22 in the CG. Fifteen patients received 1000mcg E39, and 14 received <1000mcg. There were no clinicopathologic differences between groups(all p ≥ 0.1). E39 was well-tolerated regardless of dose. DTH increased pre- to post-vaccination (5.7±1.5 mm vs 10.3±3.0 mm, p = 0.06) in the VG, and increased more in the 1000mcg group (3.8±2.0 mm vs 9.5±3.5 mm, p = 0.03). With 12 months median follow-up, the RR was 41% (VG) vs 55% (CG), p = 0.41. Among the 1000mcg patients, the RR was 13.3% vs 55% CG, p = 0.01. Estimated 2-year DFS was 85.7% in the 1000mcg group vs 33.6% in the CG (p = 0.021). CONCLUSIONS This phase I/IIa trial reveals that E39+GM-CSF is well-tolerated and elicits a strong, dose-dependent in vivo immune response. Early efficacy results are promising in the 1000 mcg dose cohort. This study proves the safety and establishes the dose of E39 for a larger prospective, randomized, controlled trial in HLA-A2+ EC and OC patients to prevent recurrence.
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4.
Pharmacotherapy for recurrent ovarian cancer: current status and future perspectives.
Matsumoto, K, Onda, T, Yaegashi, N
Japanese journal of clinical oncology. 2015;(5):408-10
Abstract
Several 'lines of therapy' that utilize cytotoxic agents and are driven by platinum-free intervals are the current standard of care for patients with recurrent ovarian cancer. For patients with platinum-resistant disease, single agent chemotherapy (pegylated liposomal doxorubicin, topotecan, gemcitabine or weekly paclitaxel) is the standard of care. For patients with platinum-sensitive disease, combination chemotherapy (carboplatin plus paclitaxel, pegylated liposomal doxorubicin or gemcitabine) is the standard of care. In addition, antiangiogenic therapy using bevacizumab is an established option. Future directions could include 'lines of therapy' with biologic agents driven by specific biologic targets. Data from antiangiogenic agents (trebananib, pazopanib and cediranib), antifolate drugs (farletuzumab and vintafolide), poly(ADP-ribose) polymerase inhibitors (olaparib and veliparib), mTOR inhibitors (everolimus and temsirolimus) and immune editing agents (nivolumab) have been summarized in this review.
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New perspectives in ovarian cancer treatment.
Schmid, BC, Oehler, MK
Maturitas. 2014;(2):128-36
Abstract
Ovarian cancer (OC) is increasingly understood as a heterogeneous disease comprising distinct subtypes of different origin that vary significantly with regard to molecular biology and clinical behaviour. Despite some limited progress in its treatment over the last decade, currently there are few therapeutic options and overall survival remains poor. Increasing knowledge about the molecular biology of ovarian cancer has led to the development of targeted therapies which promise to be more effective and to provide the basis for personalized treatment. The most successful strategies so far are employing anti-angiogenics (VEGF antibodies, tyrosine kinase inhibitors and angiopoietin antagonists) and polyadenosine diphosphate-ribose polymerase (PARP) inhibitors. Other approaches target aberrant OC signalling such as the PI3K/Akt/mTOR network, the epidermal growth factor receptor, the WEE1 tyrosine kinase and the folate receptor alpha. Immunotherapy is another promising new approach against ovarian cancer. In this area, immunotherapeutic modulation by administering autologous immune cells, such as dendritic cells (DCs), to stimulate antitumour host responses is of special interest. Finally, there is now growing evidence from clinical studies showing a survival advantage for intraperitoneal (IP) chemotherapy when compared to conventional intravenous treatment in the adjuvant setting. New strategies such as pressurized IP aerosol chemotherapy might further improve the efficacy of this approach.
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6.
The role of regulatory T cells in ovarian cancer.
Dietl, J, Engel, JB, Wischhusen, J
International journal of gynecological cancer : official journal of the International Gynecological Cancer Society. 2007;(4):764-70
Abstract
Regulatory T cells (T(reg)), also termed suppressor T cells, control self-reactive T cells in the periphery, thereby conferring protection against immunologic self-destruction. While T(reg) are essential for the prevention of autoimmunity, they also inhibit immune responses against tumor antigens. This is corroborated by an increased mortality rate associated with the presence of a high number of intratumoral T(reg). Tumor infiltration by non-T(reg), on the other hand, is predictive for a substantially longer patient survival. These clinical data suggest that ovarian cancer patients can spontaneously mount effective antitumor immune responses that are undermined by T(reg)-mediated tolerization. The present article reviews clinical and experimental findings on T(reg) in ovarian cancer, with special regard to potential therapeutic implications, which may result from the existing evidence.