Treatment Of Epithelial Ovarian Carcinoma Research Articles

The Barnase-Barstar-based pre-targeting strategy for enhanced antitumor therapy in vivo

There is a great need for novel approaches to the treatment of epithelial ovarian carcinoma, which is the leading cause of mortality from gynecological malignancies. In this study, the pre-targeting technology was used to enhance the in vivo targeting of cytotoxic module composed of nanoliposomes loaded with a truncated form of Pseudomonas aeruginosa exotoxin A (PE40) to cancer cells. Pre-targeting system used in this study is composed of bacterial ribonuclease Barnase and its natural antitoxin Barstar. Barstar, genetically fused to various engineered scaffold proteins specific to tumor-associated antigens (HER2, EpCAM) serves as a primary module for precise cancer cell recognition. Barnase conjugated to a therapeutic agent serves as a cytotoxic or secondary module for malignant cell elimination. Due to strong non-covalent interaction (KD10−14 M) of Barstar and Barnase, the primary and secondary modules efficiently interact with each other on the cell surface, which has been proven by confocal microscopy and flow cytometry. Using mice with SKOV-3 ovarian cancer xenografts, we have shown that regardless of the targeting module, the pre-targeting approach is much more effective than a single-step active targeting.

Antibody therapeutics for epithelial ovarian cancer

ABSTRACT Introduction High-grade serous ovarian carcinoma (HGSC) is an aggressive subtype of epithelial ovarian carcinoma (EOC) and remains the most lethal gynecologic cancer. A lack of effective and tolerable therapeutic options and nonspecific symptoms at presentation with advanced stage of disease are among the challenges in the management of the disease. Areas covered An overview of ovarian cancer, followed by a discussion of the current therapeutic regimes and challenges that arise during and after the treatment of EOC. We discuss different formats of antibody therapeutics and their usage in targeting validated targets implicated in ovarian cancer, as well as three emerging novel proteins as examples recently implicated in their contribution to adaptive resistance in ovarian cancer. Expert opinion Antibody therapeutics allow for a unique and effective way to target proteins implicated in cancer and other diseases, and have the potential to radically change the outcomes of patients suffering from ovarian cancer. The vast array of targets that have been implicated in ovarian cancer and yet the lack of effective therapeutic options for patients further stresses the importance of discovering novel proteins that can be targeted, as well as predictive biomarkers that can inform the stratification of patients into treatment-specific populations.

Aberrant MAPK Signaling Offers Therapeutic Potential for Treatment of Ovarian Carcinoma.

Ovarian cancer remains the most lethal gynecological malignancy worldwide due to lack of effective screening, vague early symptoms, poor description of biomarkers, and absence of effective treatment regimes. Epithelial ovarian carcinoma (EOC) is categorized into five distinct disease subtypes which collectively account for ~90% of ovarian carcinomas. Most women present at advanced stages contributing to a poor overall 5-year survival rate. Standard treatment for EOC is cytoreductive surgery and platinum-based chemotherapy; however, most patients suffer from recurrence and platinum-resistant disease, which highlights an urgent need for targeted therapy. The high frequency of molecular alterations affecting gain-of-function signaling through the RAS mitogen-activated protein kinase (MAPK) pathway in EOC has prompted pre-clinical and clinical efforts toward research into the effectiveness of MAPK pathway inhibition as a second-line treatment. The RAS/MAPK pathway is a highly conserved signal transduction cascade, often disrupted in cancer, that regulates tumorigenic phenotypes including cellular proliferation, survival, migration, apoptosis, and differentiation. Herein, the role of the MAPK pathway in EOC with emphasis on targetability of the pathway is described. Pre-clinical and clinical efforts to target MAPK signaling in EOC have identified several MAPK pathway inhibitors that offer efficacious potential for monotherapy and in combination with other compounds. Thus, inhibition of the RAS/MAPK pathway is emerging as a tractable strategy for treatment of ovarian cancer that may permit development of personalized therapy and improved prognosis for women challenged by this disease.

Tumor BRCA Testing in Epithelial Ovarian Cancers: Past and Future-Five-Years' Single-Institution Experience of 762 Consecutive Patients.

Simple SummaryTumor BRCA testing is crucial in the clinical management of women affected by epithelial ovarian cancer (EOC). In the present study, we aimed to report the results of five years of experience in tumor BRCA testing performed in a single-institution diagnostic setting. We profiled 762 consecutive EOC patients with a failure rate of less than 1% and less than two weeks of turnaround time, which is consistent with the clinical needs. We identified 23.4% of cases with pathogenic/likely pathogenic mutations, including 76% of patients affected by germline and 24% by somatic alterations. Here, we proposed a comprehensive and multidisciplinary clinical workflow that could be successfully followed for the identification of somatic as well as germline alterations, maximizing the benefit of BRCA testing both from a therapeutic and risk assessment perspective.The establishment of PARP inhibitors in the treatment of epithelial ovarian carcinoma (EOC) has prompt BRCA assessment at the time of diagnosis. We described our five years of experience of tumor BRCA testing, as part of a multidisciplinary workflow for the management of EOC patients. We used a BRCA next-generation sequencing (NGS) test for profiling formalin-fixed, paraffin-embedded (FFPE) EOCs of 762 consecutive patients, with a success rate of 99.7% and a median turnaround time of 12 days. We found 178 (23.4%) cases with pathogenic/likely pathogenic (P/LP) mutations, 74 (9.7%) cases with variants of uncertain significance and 508 (66.8%) wild type tumors. Among 174 patients without P/LP mutations and investigated with multiple-ligation probe-amplification analysis on peripheral blood, two (1.1%) were positive for large rearrangements. Patients with P/LP alterations and/or with positive family history were referred to genetic counselling. Comparing tumor and blood NGS test results of 256 patients, we obtained a tumor test negative predictive value of 100% and we defined 76% of P/LP alterations as germline and 24% as somatic variants. The proposed workflow may successfully identify EOC patients with BRCA1/2 alteration, guiding both therapeutic and risk assessment clinical decisions.

What underlies the observed hospital volume-outcome relationship?

BackgroundStudies of the hospital volume-outcome relationship have highlighted that a greater volume activity improves patient outcomes. While this finding has been known for years, most studies to date have failed to delve into what underlies this relationship.ObjectiveThis study aimed to shed light on the basis of the hospital volume effect on patient outcomes by comparing treatment modalities for epithelial ovarian carcinoma patients.DataAn exhaustive dataset of 355 patients in first-line treatment for Epithelial Ovarian Carcinoma (EOC) in 2012 in three regions of France was used. These regions account for 15% of the metropolitan French population.MethodsIn the presence of endogeneity induced by a reverse causality between hospital volume and patient outcomes, we used an instrumental variable approach. Hospital volume of activity was instrumented by the distance from patients’ homes to their hospital, the population density, and the median net income of patient municipalities.ResultsBased on our parameter estimates, we found that the rate of complete tumor resection would increase by 15.5 percentage points with centralized care, and by 8.3 percentage points if treatment decisions were coordinated by high-volume centers compared to decentralized care.ConclusionAs volume alone is an imperfect correlate of quality, policy-makers need to know what volume is a proxy for in order to devise volume-based policies.

Formulation of an ovarian cancer vaccine with the squalene-based AddaVax adjuvant inhibits the growth of murine epithelial ovarian carcinomas.

PurposeEpithelial ovarian carcinoma (EOC) is the most lethal of all human gynecologic malignancies. We previously reported that vaccination of female mice with the extracellular domain of anti-Müllerian hormone receptor II (AMHR2-ED) in complete Freund’s adjuvant (CFA) generates AMHR2-ED specific immunoglobulin G (IgG) that provides prevention and therapy against murine EOCs. Although CFA is the “gold standard” adjuvant in animal studies, it is not approved for human use because it often induces painful granulomas and abscesses. Thus, the objective of this study is to identify an alternative adjuvant to CFA for use in our ovarian cancer vaccine clinical trials.Materials and MethodsBecause it has been used successfully without serious adverse effects in numerous human clinical trials, we selected the IgG-inducing squalene-based adjuvant, AddaVax™, for evaluation of its ability to facilitate vaccine-induced prevention and treatment of EOC in mice. To this end, we immunized female C57BL/6 mice with recombinant mouse AMHR2-ED emulsified with either AddaVax or CFA as adjuvant and compared the results.ResultsWe found that formulation of the AMHR2-ED vaccine with AddaVax adjuvant induced high serum titers of IgG and significant inhibition of EOC growth with significantly enhanced overall survival of mice using both prevention and therapeutic protocols. These results were compared favorably with results obtained using CFA as an adjuvant in the AMHR2-ED vaccine.ConclusionOur data indicate that the AMHR2-ED vaccine formulated with AddaVax may be used in human clinical trials and thereby serve as a novel and effective way to control human EOC.

Ovarian Carcinoma with Peritoneal Metastasis: Rethinking of Management

Epithelial Ovarian Carcinoma (EOC), a type of cancer that is usually diagnosed in advanced stages. To date, standard treatment of EOC is surgery with neoadjuvant or adjuvant platin and taxane based systemic chemotherapy. Hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) is considered in cases of recurrence of EOC. HIPEC has been accepted as a gold standart for the treatment of pseudomyoxoma peritonei of ovarian and appendiceal origin. More recently, a randomized clinical trial supports that HIPEC is a promising treatment option for peritoneal metastasis (PM) of ovarian cancer (OC) in surgical series. HIPEC is also reported to be an effective treatment option in primary and recurrent cancer cases with PM of OC. As a result, the standardization and optimization of the HIPEC technique, determination of patient subgroups with PM of the OC responding to treatments, personalized evaluation and the treatments currently carried out by the multidisciplinary team still need to be re-evaluated.
 In this review, it is aimed to update the standard treatment approach in case of peritoneal metastasis of ovarian cancer, along with the systemic treatments and HIPEC treatment approaches combined with surgery.

BTLA blockade enhances Cancer therapy by inhibiting IL-6/IL-10-induced CD19high B lymphocytes

BackgroundThe standard treatment for epithelial ovarian carcinoma (EOC) is surgery followed by platinum/paclitaxel-based chemotherapy, but the overall survival rate is poor. The purpose of this study was to investigate the therapeutic potential of chemotherapy combined with inhibition of B and T lymphocyte attenuator (BTLA) for clinical use to treat EOC.MethodsInitially, we evaluated the potential application of chemotherapy combined with anti-BTLA antibody in an animal model. We then analyzed the distribution and regulation of BTLA expression on immunocytes in vitro. Finally, we examined the correlation between BTLA expression levels in cancerous tissues and prognosis in 254 EOC cases.ResultsThe combination of chemotherapy and anti-BTLA antibody for inhibiting BTLA significantly reduced peritoneal tumor volume and extended survival in tumor-bearing mice. In addition, BTLA could be identified mostly on B lymphocytes, especially on CD19hi B cells, rather than on T lymphocytes and natural killer cells. Under regulation of interleukins 6 and 10, more BTLA+CD19hi B lymphocytes could be induced through AKT and STAT3 signaling pathways. Detectable BTLA expression in ovarian cancerous tissues was associated with worse disease-free and overall survivals of EOC patients.ConclusionsBTLA detected in cancerous tissues can predict poor outcome of EOC patients. Inhibition of BTLA combined with chemotherapy can elevate immune activation and generate potent anti-tumor effects. Thus, the combination of chemotherapy and anti-BTLA antibody may hold potential clinical application for the treatment of EOC patients.Trial registrationThe Trial Registration Number was NCT00854399.

PCN223 - WHAT UNDERLIES THE OBSERVED HOSPITAL VOLUME-OUTCOME RELATIONSHIP?

Studies of the hospital volume-outcome relationship have highlighted that a greater volume activity improves patient outcomes. While this finding has been known for years in health services research, most studies to date have failed to delve into what underlies this relationship. This study aimed to shed light on the basis of the hospital volume effect by comparing treatment modalities for epithelial ovarian carcinoma (EOC) patients. We used three clinical databases that contained exhaustive datasets of patients in first-line treatment for EOC in 2012 in three regions of France (n=355). Hospital volume activity was instrumented by the distance from patients’ homes to their hospital, and the population density. We used complete tumor resection as a quality indicator. We found that higher volume hospitals appear to more often make the right decisions in regard to how to treat patients, which contributes to the positive impact of hospital volume activities on patient outcomes. Based on our parameter estimates, we found that the rate of complete tumor resection would increase by 10% with centralized care, and by 6% if treatment decisions were coordinated by high volume centers compared to the ongoing organization of care. In both scenarios, the use of neoadjuvant chemotherapy would increase by 10%. As volume alone is an imperfect correlate of quality, policy makers need to know what volume is a proxy for in order to devise volume-based policies. Centralized care at high volume hospitals was the scenario that led to the highest average patient outcome. However, several barriers, such as the increase in patient travel distances, have prevented such a reform of the organization of care from being applied. An intermediate solution between centralized and decentralized care could be to make lower volume hospitals benefit from the expertise of higher volume hospitals when making treatment decisions.

Preclinical development of a therapeutic antibody for the treatment of epithelial ovarian carcinoma

Background: Despite active research in ovarian cancer immunotherapy, standard of care for ovarian cancer remains surgery and (neo)adjuvant chemotherapy. Patients often develop secondary resistance to chemotherapy, leading to recurrence. Since most mouse models have had a poor translational efficiency so far, there is a need for new therapy development strategies. We here present a mostly human-based pipeline that we have used for target identification and drug development and testing.

There is Currently no Role of HIPEC in Epithelial Ovarian Cancer in Routine Clinical Practice

Epithelial ovarian carcinoma (EOC) accounts for majority of ovarian cancers and leading cause of death because of gynecological cancers. Primary reason for high mortality associated with ovarian carcinoma is late diagnosis, as 70–80% of patients are diagnosed at an advanced stage, where treatment response is poor. There have been various developments in management of ovarian cancers to improve treatment responses and outcomes from more aggressive surgery to introduction of new chemotherapeutic agents and exploring different routes/protocols to deliver chemotherapy. Hyperthermic intraperitoneal chemotherapy (HIPEC) has been shown to be effective in treating cancers of the appendix, colon, rectum, peritoneal carcinomas and mesotheliomas. With the same rationale, it is also being evaluated and practiced for treatment of epithelial ovarian carcinoma. This provides us with a classical example of conflict between evidence-based medicine and innovations in treatment. We need to have a close look at the data that are available today which is largely heterogenous, incomplete and essentially largely single institutional experiences. Also we need to evaluate the cost and morbidity associated with the procedure. In this review, we have evaluated the current available evidence for use of HIPEC in ovarian carcinoma and the data are still not mature for us to use HIPEC for ovarian carcinoma currently. It is essential to wait for more evidence to merge in favor of HIPEC, before we use it as a primary modality of treatment for ovarian carcinoma.

The evolving role of cytopathology in the era of neoadjuvant chemotherapy for the accurate pathologic diagnosis of epithelial ovarian cancer.

The evolving role of cytopathology in the era of neoadjuvant chemotherapy for the accurate pathologic diagnosis of epithelial ovarian cancer.

ELF5 in epithelial ovarian carcinoma tissues and biological behavior in ovarian carcinoma cells.

The expression of E74-like factor 5 (ELF5) in epithelial ovarian carcinoma tissues and its effects on biological behavior in ovarian carcinoma cells were assessed in search for a new approach for gene treatment of epithelial ovarian carcinoma. RT-PCR technology was applied to detect the expression of ELF5 mRNA in epithelial ovarian carcinoma (n=49), borderline ovarian epithelial tumor (n=19), benign ovarian epithelial tumor (n=31) and normal ovarian tissues (n=40). Then, we transfected recombinant plasmid pcDNA3.1-ELF5+EGFP into human ovarian carcinoma SKOV3 cells (recombinant plasmid group) in vitro and screened out stably transfected cells to conduct multiplication culture. Western blot analysis was performed to detect the expression of ELF5 protein in the different groups. Flow cytometry was employed to detect cell apoptosis and cycles. ELF5 mRNA in epithelial ovarian carcinoma and borderline ovarian epithelial tumor tissues were significantly lower (P<0.05) than those in benign ovarian epithelial tumor and normal ovarian tissues. ELF5 protein expression in the cells of recombinant plasmid group was significantly higher compared with empty plasmid and blank control groups. The capacity of cell reproductive recombinant plasmid group at each time point decreased (P<0.05). Flow cytometry detection showed that 67.03% of cells in recombinant plasmid group was blocked in G0/G1 phase (P<0.05), compared with empty plasmid group (37.17%) and blank control group (38.24%). Apoptotic rate of recombinant plasmid group was significantly lower (31.4±1.9%; P<0.05), compared with that of empty plasmid group (9.1±2.2%) and blank control group (8.7±1.5%), and the differences were statistically significant. In conclusion, ELF5 interfered with cell cycle of human ovarian carcinoma SKOV3 cells and promoted apoptosis of human ovarian carcinoma SKOV3 cells inhibiting their growth and invasive capacity; and thus providing a new approach to gene treatment of ovarian carcinoma.

Ovarian carcinoma: An overview of current status

&lt;p&gt;Ovarian carcinoma is one of the leading causes of morbidity and mortality associated with carcinomas affecting women. It comprises a heterogeneous group of neoplasms that represents the seventh most lethal malignancy in women worldwide, and is a major cause of death from gynecological carcinoma. Specific to different geographical locations all over the globe, there are variations in the magnitude and trends of ovarian carcinoma, and the scenario of the disease keeps changing. As such, it is necessary to update and review the existing study on ovarian carcinoma. Reviews on ovarian cancer from 2000 to 2015 were extracted from PubMed and Google Scholar, and a few selected landmark studies that incorporated old data were also included. The focus of the present study is to consolidate an updated global view on epithelial ovarian carcinoma, the most prevalent type of ovarian carcinoma. This article covers the epidemiology, types, diagnosis, prognosis, and treatment of epithelial ovarian carcinoma.&lt;/p&gt;

The HDACi Panobinostat Shows Growth Inhibition Both In Vitro and in a Bioluminescent Orthotopic Surgical Xenograft Model of Ovarian Cancer.

BackgroundIn most epithelial ovarian carcinomas (EOC), epigenetic changes are evident, and overexpression of histone deacetylases (HDACs) represents an important manifestation. In this study, we wanted to evaluate the effects of the novel HDAC inhibitor (HDACi) panobinostat, both alone and in combination with carboplatin, on ovarian cancer cell lines and in a murine bioluminescent orthotopic surgical xenograft model for EOC.MethodsThe effects of panobinostat, both alone and in combination with carboplatin, on proliferation and apoptosis in ovarian cancer cell lines, were evaluated using colony and WST-1 assays, Hoechst staining and flow cytometry analysis. In addition, mechanisms were characterised by western blotting and phosphoflow analysis. Immuno-deficient mice were engrafted orthotopically with SKOV-3luc+ cells and serial bioluminescence imaging monitored the effects of treatment with panobinostat and/or carboplatin and/or surgery. Survival parameters were also measured.ResultsPanobinostat treatment reduced cell growth and diminished cell viability, as shown by the induced cell cycle arrest and apoptosis in vitro. We observed increased levels of cleaved PARP and caspase-3, downregulation of cdc2 protein kinase, acetylation of H2B and higher pH2AX expression. The combined administration of carboplatin and panobinostat synergistically increased the anti-tumour effects compared to panobinostat or carboplatin treatment alone. In our novel ovarian cancer model, the mice showed significantly higher rates of survival when treated with panobinostat, carboplatin or a combination of both, compared to the controls. Panobinostat was as efficient as carboplatin regarding prolongation of survival. No significant additional effect on survival was observed when surgery was combined with carboplatin/panobinostat treatment.ConclusionsPanobinostat demonstrates effective in vitro growth inhibition in ovarian cancer cells. The efficacy of panobinostat and carboplatin was equal in the orthotopic EOC model used. We conclude that panobinostat is a promising therapeutic alternative that needs to be further assessed for the treatment of EOC.

The increasing use of neoadjuvant chemotherapy for the treatment of epithelial ovarian carcinoma in the United States: A study of practice patterns

The increasing use of neoadjuvant chemotherapy for the treatment of epithelial ovarian carcinoma in the United States: A study of practice patterns

Migration-inducing gene 7 promotes tumorigenesis and angiogenesis and independently predicts poor prognosis of epithelial ovarian cancer.

Epithelial ovarian carcinomas (EOC) cause more mortality than any other cancer of the female reproductive system. New therapeutic approaches to reduce EOC mortality have been largely unsuccessful due to the poor understanding of the mechanisms underlying EOC proliferation and metastasis. Progress in EOC treatment is further hampered by a lack of reliable prognostic biomarkers for early risk assessment. In this study, we identify that Migration-Inducting Gene 7 (MIG-7) is specifically induced in human EOC tissues but not normal ovaries or ovarian cyst. Ovarian MIG-7 expression strongly correlated with EOC progression. Elevated MIG-7 level at the time of primary cytoreductive surgery was a strong and independent predictor of poor survival of EOC patients. Cell and murine xenograft models showed that MIG-7 was required for EOC proliferation and invasion, and MIG-7 enhanced EOC-associated angiogenesis by promoting the expression of vascular endothelial growth factor. Inhibiting MIG-7 by RNA interference in grafted EOC cells retarded tumor growth, angiogenesis and improved host survival, and suppressing MIG-7 expression with a small molecule inhibitor D-39 identified from the medicinal plant Liriope muscari mitigated EOC growth and invasion and specifically abrogated the expression of vascular endothelial growth factor. Our data not only reveal a critical function of MIG-7 in EOC growth and metastasis and support MIG-7 as an independent prognostic biomarker for EOC, but also demonstrate that therapeutic targeting of MIG-7 is likely beneficial in the treatment of EOC.

Immunotherapy for ovarian cancer.

All work referenced herein relates to treatment of epithelial ovarian carcinomas, as their treatment differs from ovarian germ cell cancers and other rare ovarian cancers, the treatments of which are addressed elsewhere. Fallopian tube cancers and primary peritoneal adenocarcinomatosis are also generally treated as epithelial ovarian cancers. The standard of care initial treatment of advanced stage epithelial ovarian cancer is optimal debulking surgery as feasible plus chemotherapy with a platinum plus a taxane agent. If this front-line approach fails, as it too often the case, several FDA-approved agents are available for salvage therapy. However, because no second-line therapy for advanced-stage epithelial ovarian cancer is typically curative, we prefer referral to clinical trials as logistically feasible, even if it means referring patients outside our system. Immune therapy has a sound theoretical basis for treating carcinomas generally, and for treating ovarian cancer in particular. Advances in understanding the immunopathogenic basis of ovarian cancer, and the immunopathologic basis for prior failures of immunotherapy for it and other carcinomas promises to afford novel treatment approaches with potential for significant efficacy, and reduced toxicities compared with cytotoxic agents. Thus, referral to early phase immunotherapy trials for ovarian cancer patients that fail conventional treatment merits consideration.

CXCR7 signaling induced epithelial-mesenchymal transition by AKT and ERK pathways in epithelial ovarian carcinomas.

Epithelial-mesenchymal transition (EMT) plays an important role in oncogenesis, through which cancer cells acquire an invasion and metastasis capacity. Notably, the chemokine receptor CXCR7 and its ligands CCL19 can also facilitate lymph node metastasis in epithelial ovarian carcinomas. Here, we assumed that CXCR7 might be involved in the EMT process of epithelial ovarian carcinomas. In our study, CXCR7 activation and inhibition in SKOV3 were induced with exogenous CCL19 and CXCR7 small interfering RNA (CXCR7 siRNA), respectively. AKT and ERK protein of CXCR7 pathways as well as biomarkers (vimentin, snail, N-cadherin, and E-cadherin) of EMT were detected using the Western blot. Our results showed that CCL19 can induce AKT and ERK phosphorylation in a dose-dependent fashion; however, CXCR7 siRNA efficaciously suppressed CCL19-induced AKT and ERK phosphorylation in comparison with control siRNA. Importantly, CCL19 alone treatment can upregulate the expression of vimentin, snail, and N-cadherin of SKOV3 and downregulate the expression of E-cadherin. Conversely, knockdown of CXCR7 did not reveal any changes compared with CCL19 and the control. In conclusion, these findings demonstrate that EMT can be regulated by the CCL19/CXCR7 axis in epithelial ovarian carcinomas and then involved in the tumor cell invasion and metastasis process via activation of AKT and ERK pathways. Our study lays a new foundation for the treatment of epithelial ovarian carcinomas through antagonizing CXCR7.

The efficacy and safety of Oxaliplatin-Vinorelbine as a second-line chemotherapy combination in patients with platinum-resistant pretreated epithelial ovarian cancer: A retrospective study

Purpose: The main purpose of this study was to analyze the effects and tolerability of Oxaliplatin-Vinorelbine combination on Platinum-resistant epithelial ovarian carcinoma (EOC) patients. Methods: A single centered retrospective study comprising of 34 patients was conducted, and all 34 patients were treated with Vinorelbine 30 mg/m 2 on day 1 and 8 along with Oxaliplatin 100 mg/m 2 on day 1 of 3 weeks treatment cycle following progressive platinum-resistant EOC. Results: The combination showed an overall response rate (ORR) of 18% (95% CI, 4.4 - 31.6) where 2 (6%) patients had complete response and 4 (12%) patients had partial response. Stable disease was observed in 9 (26%) patients and progressive disease in 19 (56%) patients. Median diseases free survival, median relapse free survival and median time to progression was 17.05 months, 4.4 months, and 1.25 months, respectively. Hematological toxicities were mild; only 1 (2.9%) patient had G3 anemia and major non-hematological toxicities include nausea-vomiting, diarrhea, constipation, hepatotoxicity, fatigueness and alopecia, which are mainly limited to G1-G2 and reversible. Conclusion: The effect of this combination is moderate as a second line treatment of platinum resistant EOC; however, in comparison with other regimens of Vinorelbine and Oxaliplatin, the activity is substandard but the toxicity profile is well tolerable. Further multicenter evaluation is needed for the better understanding of the therapeutic efficacy of the combination.