Trials With Impact on Clinical Management: First Line

2009 ◽  
Vol 19 (Suppl 2) ◽  
pp. S55-S62 ◽  
Author(s):  
Michael A. Bookman
Keyword(s):  
Ovarian Cancer ◽  
Cancer Biology ◽  
Treatment Options ◽  
Tumor Biology ◽  
Chemotherapy Resistance ◽  
Treatment Strategies ◽  
Weekly Dose ◽  
Primary Therapy ◽  
Phase 3 ◽  
Standard Regimen

Introduction:Advanced-stage epithelial ovarian cancer is generally managed with cytoreductive surgery and chemotherapy consisting of carboplatin and paclitaxel. Although initially responsive, most tumors recur and demonstrate progressive chemotherapy resistance. During the last 20 years, many thousands of women have participated in international front-line phase 3 trials that have contributed to our understanding of ovarian cancer biology and helped to define optimal treatment strategies. Emerging data from these trials need to be interpreted within an evolving paradigm of cancer biology, disease management, and availability of clinical resources.Methods:Survey of recent phase 3 trials and emerging principles of ovarian tumor biology.Results:There is no evidence that adding a third cytotoxic agent improves clinical outcomes. However, weekly dose-dense scheduling of paclitaxel appears superior to standard dosing.Conclusion:Primary therapy with carboplatin and paclitaxel remains a well-tolerated standard regimen, including the option of weekly paclitaxel dosing. Data are awaited from completed trials incorporating bevacizumab. Emerging biological paradigms will contribute to individualized treatment options in the future.

scholarly journals Modeling the Tumor Microenvironment of Ovarian Cancer: The Application of Self-Assembling Biomaterials

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5745
Author(s):  
Ana Karen Mendoza-Martinez ◽  
Daniela Loessner ◽  
Alvaro Mata ◽  
Helena S. Azevedo
Keyword(s):  
Ovarian Cancer ◽  
Tumor Microenvironment ◽  
Materials Science ◽  
Treatment Options ◽  
Tumor Biology ◽  
3D Models ◽  
Gynecologic Malignancies ◽  
Cell Behaviors ◽  
Self Assembling ◽  
Key Driver

Ovarian cancer (OvCa) is one of the leading causes of gynecologic malignancies. Despite treatment with surgery and chemotherapy, OvCa disseminates and recurs frequently, reducing the survival rate for patients. There is an urgent need to develop more effective treatment options for women diagnosed with OvCa. The tumor microenvironment (TME) is a key driver of disease progression, metastasis and resistance to treatment. For this reason, 3D models have been designed to represent this specific niche and allow more realistic cell behaviors compared to conventional 2D approaches. In particular, self-assembling peptides represent a promising biomaterial platform to study tumor biology. They form nanofiber networks that resemble the architecture of the extracellular matrix and can be designed to display mechanical properties and biochemical motifs representative of the TME. In this review, we highlight the properties and benefits of emerging 3D platforms used to model the ovarian TME. We also outline the challenges associated with using these 3D systems and provide suggestions for future studies and developments. We conclude that our understanding of OvCa and advances in materials science will progress the engineering of novel 3D approaches, which will enable the development of more effective therapies.

scholarly journals Matrine inhibits the development and progression of ovarian cancer by repressing cancer associated phosphorylation signaling pathways

2019 ◽  
Vol 10 (10) ◽  
Author(s):  
Xi Zhang ◽  
Guoqing Hou ◽  
Andong Liu ◽  
Hui Xu ◽  
Yang Guan ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Side Effects ◽  
Cancer Cells ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Chemotherapy Resistance ◽  
Treatment Strategies ◽  
Ovarian Cancer Cells

Abstract Ovarian cancer remains the most lethal gynecologic malignancy with late detection and acquired chemoresistance. Advanced understanding of the pathophysiology and novel treatment strategies are urgently required. A growing body of proteomic investigations suggest that phosphorylation has a pivotal role in the regulation of ovarian cancer associated signaling pathways. Matrine has been extensively studied for its potent anti-tumor activities. However, its effect on ovarian cancer cells and underlying molecular mechanisms remain unclear. Herein we showed that matrine treatment inhibited the development and progression of ovarian cancer cells by regulating proliferation, apoptosis, autophagy, invasion and angiogenesis. Matrine treatment retarded the cancer associated signaling transduction by decreasing the phosphorylation levels of ERK1/2, MEK1/2, PI3K, Akt, mTOR, FAK, RhoA, VEGFR2, and Tie2 in vitro and in vivo. Moreover, matrine showed excellent antitumor effect on chemoresistant ovarian cancer cells. No obvious toxic side effects were observed in matrine-administrated mice. As the natural agent, matrine has the potential to be the targeting drug against ovarian cancer cells with the advantages of overcoming the chemotherapy resistance and decreasing the toxic side effects.

Individualizing Treatment Decisions for Older Adults with Hematologic Malignancies

2013 ◽  
pp. 208-219
Author(s):  
Heidi D. Klepin ◽  
David Rizzieri ◽  
Antonio Palumbo ◽  
Valeria Magarotto ◽  
Barbara Eichhorst
Keyword(s):  
Older Adults ◽  
Treatment Options ◽  
Allogeneic Bone Marrow Transplantation ◽  
Tumor Biology ◽  
Treatment Strategies ◽  
Hematologic Malignancies ◽  
Lymphocytic Leukemia ◽  
Allogeneic Bone ◽  
Functional Impairments ◽  
Therapeutic Decisions

Hematologic malignancies are a common cause of morbidity and mortality among older adults, who represent the majority of patients diagnosed with these diseases. Treatment options and disease outcomes have improved in recent years because of the development of novel treatment strategies and the design of elderly-specific clinical trials. Despite this, extrapolation of clinical trial data to patients routinely seen in practice is challenging because of the presence of multimorbidity and functional impairments. Individualized treatment decision making requires not only an understanding of underlying tumor biology but also careful estimation of an older patient's anticipated ability to withstand the stresses of therapy. This article will discuss approaches to standardizing patient assessment strategies and tailoring therapeutic decisions for older adults with hematologic malignancies with a focus on acute myeloid leukemia (AML), allogeneic bone marrow transplantation, multiple myeloma (MM), and chronic lymphocytic leukemia (CLL).

Management of recurrent ovarian cancer: when platinum-based regimens are not a therapeutic option

2019 ◽  
Vol 29 (9) ◽  
pp. 1431-1436 ◽  
Author(s):  
Alice Bergamini ◽  
Luca Bocciolone ◽  
Andrei Fodor ◽  
Massimo Candiani ◽  
Giorgia Mangili
Keyword(s):  
Ovarian Cancer ◽  
Personalized Medicine ◽  
Recurrent Disease ◽  
Therapeutic Option ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Recurrent Ovarian Cancer ◽  
Best Management ◽  
Free Interval ◽  
Treatment Alternatives

Ovarian cancer relapses have been traditionally classified according to the platinum-free interval, leading to an arbitrary categorization of possible scenarios and treatment options. Its relevance in assessing treatment strategies has been revised in the last several years, as the panorama is constantly changing in the era of personalized medicine and targeted therapies. Factors to be considered while defining the best management of recurrent disease, and, consequently, the available treatment alternatives are increasing. Platinum remains one of the milestones of ovarian cancer treatment, but for some patients it might not be an ideal choice for several reasons other than limited platinum sensitivity. This review aims to analyze the scenarios in which platinum is not considered suitable in the management of patients with recurrent ovarian cancer, and the currently available alternatives.

scholarly journals siRNA-Conjugated Nanoparticles to Treat Ovarian Cancer

2019 ◽  
Vol 24 (2) ◽  
pp. 137-150 ◽  
Author(s):  
Christopher Halbur ◽  
Niharika Choudhury ◽  
Michael Chen ◽  
Jun Hyuk Kim ◽  
Eun Ji Chung
Keyword(s):  
Ovarian Cancer ◽  
Targeted Delivery ◽  
Target Genes ◽  
Treatment Options ◽  
Chemotherapy Resistance ◽  
The United States ◽  
Tumor Burden ◽  
Ovarian Cancer Cells ◽  
Reduce Tumor Burden ◽  
Sirna Therapy

Ovarian cancer is the fifth-most lethal cancer among women due to a lack of early detection and late-stage treatment options, and it is responsible for more than 14,000 deaths each year in the United States. Recently, there have been advances in RNA interference therapy, specifically with small interfering RNA (siRNA), to reduce tumor burden for ovarian cancer via gene down-regulation. However, delivery of siRNA poses its own challenges, as siRNA is unstable in circulation, is unable to be effectively internalized by cells, and may cause toxicity in off-target sites. To address such challenges, nanoparticle carriers have emerged as delivery platforms for the biocompatible, targeted delivery of siRNA-based therapies. Several preclinical studies have shown the promising effects of siRNA therapy to reduce chemotherapy resistance and proliferation of ovarian cancer cells. This review evaluates the recent advances, clinical applications, and future potential of nanoparticle-mediated delivery of siRNA therapeutics to target genes implicated in ovarian cancer.

scholarly journals Non-Coding RNAs Mediate Chemotherapy Resistance in Ovarian Cancer

2017 ◽  
Author(s):  
Yang Shao ◽  
Hui Li ◽  
Ran Du ◽  
Jiao Meng ◽  
Gong Yang
Keyword(s):  
Ovarian Cancer ◽  
Chemotherapy Resistance ◽  
Treatment Strategies ◽  
Research Literature ◽  
Relevant Research ◽  
Regulate Gene Expression ◽  
Gynecological Malignancy ◽  
Stage Disease ◽  
Non Coding Rnas ◽  
Generation Sequencing

With the advancement of next generation sequencing in past several years, a rising number of non-coding RNAs have been found as new actors to regulate gene expression. Non-coding RNAs not only play important roles in carcinogenesis, but also affect the clinical treatment strategies. They have been proved to be deeply correlated with chemoresistance in several cancers. Ovarian cancer is the leading cause of death in gynecological malignancy, with low 5-year survival rate. Most patients are identified when they have late-stage disease. This review mainly makes a compilation of the most relevant research literature in this field with the purpose of shedding light on the relation between ncRNAs and chemoresistance in ovarian cancer.

scholarly journals Evolving treatment strategies of brain metastases from breast cancer: current status and future direction

2020 ◽  
Vol 12 ◽  
pp. 175883592093611 ◽  
Author(s):  
Jae Sik Kim ◽  
In Ah Kim
Keyword(s):  
Breast Cancer ◽  
Treatment Options ◽  
Tumor Biology ◽  
Local Treatment ◽  
Treatment Strategies ◽  
Current Treatment ◽  
Current Status ◽  
Breast Cancer Patients ◽  
Antitumor Effects ◽  
Systemic Treatments

Remarkable progress in breast cancer treatment has improved patient survival, resulting in an increased incidence of brain metastasis (BM). Current treatment options for BM are limited and are generally used for palliative purposes. Historically, local treatment, consisting of radiotherapy and surgery, is the standard of care due to delivery limitations of systemic treatments through the blood–brain barrier. However, as novel biological mechanisms for tumors and BM have been discovered, several innovative systemic agents, such as small-molecular-targeted therapy and immunotherapy, have begun to change the treatment paradigm. In addition, efforts to maximize antitumor effects have been attempted using combination therapy, informed by tumor biology. In this comprehensive review, we will highlight various clinical trials investigating the treatment of BM in breast cancer patients, discuss presently available treatment options, and suggest potential directions of future therapeutic targets.

scholarly journals Recent Advances in Integrative Multi-Omics Research in Breast and Ovarian Cancer

2021 ◽  
Vol 11 (2) ◽  
pp. 149 ◽  
Author(s):  
Christen A. Khella ◽  
Gaurav A. Mehta ◽  
Rushabh N. Mehta ◽  
Michael L. Gatza
Keyword(s):  
Ovarian Cancer ◽  
Disease Progression ◽  
Therapeutic Response ◽  
Tumor Biology ◽  
Treatment Strategies ◽  
Signaling Networks ◽  
Molecular Heterogeneity ◽  
Breast And Ovarian Cancer ◽  
Recent Advances ◽  
The Impact

The underlying molecular heterogeneity of cancer is responsible for the dynamic clinical landscape of this disease. The combination of genomic and proteomic alterations, including both inherited and acquired mutations, promotes tumor diversity and accounts for variable disease progression, therapeutic response, and clinical outcome. Recent advances in high-throughput proteogenomic profiling of tumor samples have resulted in the identification of novel oncogenic drivers, tumor suppressors, and signaling networks; biomarkers for the prediction of drug sensitivity and disease progression; and have contributed to the development of novel and more effective treatment strategies. In this review, we will focus on the impact of historical and recent advances in single platform and integrative proteogenomic studies in breast and ovarian cancer, which constitute two of the most lethal forms of cancer for women, and discuss the molecular similarities of these diseases, the impact of these findings on our understanding of tumor biology as well as the clinical applicability of these discoveries.

scholarly journals The Impact of Body Weight on Ovarian Cancer Outcomes

2011 ◽  
Vol 21 (9) ◽  
pp. 1601-1605 ◽  
Author(s):  
Floor J. Backes ◽  
Christa I. Nagel ◽  
Elizabeth Bussewitz ◽  
Jessica Donner ◽  
Erinn Hade ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Confidence Interval ◽  
Cancer Biology ◽  
Advanced Ovarian Cancer ◽  
Normal Weight ◽  
Primary Therapy ◽  
Cancer Outcomes ◽  
Poor Prognostic Factor ◽  
Increased Risk ◽  
The Impact

BackgroundObesity is a known risk factor and poor prognostic factor for many comorbidities including cancer. However, the influence of body mass index (BMI) on ovarian cancer outcomes is inconclusive. Therefore, the objective of this study was to evaluate the impact of BMI and weight changes on survival in patients with advanced ovarian cancer after primary treatment.MethodsAll patients with a diagnosis of advanced epithelial ovarian cancer from January 2000 to December 2007 undergoing primary cytoreductive surgery and adjuvant chemotherapy were identified. Patients were divided into 3 categories: underweight/normal weight (BMI, <25 kg/m2), overweight (BMI, 25–30 kg/m2), and obese (BMI, >30 kg/m2). Adjusted hazard ratios for progression-free survival (PFS) and overall survival (OS) were calculated via Cox proportional hazards models.ResultsOne hundred ninety-eight patients met the inclusion criteria. For all patients, the mean BMI was 26 kg/m2 (range, 16.4–49.1 kg/m2), with 43% of patients being classified as normal weight, 29% overweight, and 28% as obese. Median 5-year OS was 48.2 months (95% confidence interval, 16.4–49.1 months), and no differences in OS were noted between BMI groups. Unadjusted median PFS for patients with normal weight was 13.7 months, compared with 15.5 and 17.9 months for the overweight and obese groups. Adjusted analysis of BMI over time indicates a trend of increased risk for patients who gain weight in the 6 months after primary therapy on disease progression (hazard ratio, 1.68; 95% confidence interval, 0.87–3.26).ConclusionsAfter adjustment for confounders, such as stage, grade, histology, age, and debulking status, data suggest a trend toward a shorter PFS in patients with a normal BMI. However, OS was not significantly related to BMI, and weight change in the 6 months after completion of treatment had no effect on PFS or OS. Further research should be directed at elucidating relationships between weight and cancer biology.

scholarly journals Case 1 – Stage IV low-grade serous ovarian carcinoma management in an elderly patient

2017 ◽  
Vol 5 (2) ◽  
pp. 39-45
Author(s):  
Luisa Sánchez-Lorenzo ◽  
Antonio González-Martín ◽  
David M. Gershenson
Keyword(s):  
Ovarian Cancer ◽  
Hormone Therapy ◽  
Histopathological Examination ◽  
Tumor Biology ◽  
Treatment Strategies ◽  
Progesterone Receptors ◽  
Stage Iv ◽  
Initial Assessment ◽  
Low Grade ◽  
Serous Ovarian Cancer

Recurrent low-grade serous ovarian cancer (LGSOC) is considered relatively chemoresistant; until more effective chemotherapy approaches become available, surgical management remains the mainstay of treatment. However, some subtypes of LGSOC behave distinctly differently from high-grade SOC. The upregulation of estrogen and progesterone receptors in ovarian cancer suggests hormone therapy as a possible treatment modality. Our patient was a 75-year-old woman with advanced low-grade papillary serous ovarian cancer. In consultation, supported by appropriate histopathological examination and immunohistochemical study to guide the treatment decisions, our Gynaecological Oncology Multi-Disciplinary Team recommended primary debulking surgery. The patient underwent surgery followed by hormone therapy with letrozole, after declining bevacizumab-containing adjuvant chemotherapy. Eighteen months of ongoing monitoring has shown no signs of progressive disease and stable tumor markers. This case highlights the importance of initial assessment by a multidisciplinary team experienced in gynecological oncology, together with knowledge of the tumor biology, to determine effective treatment strategies for the management of advanced LGSOC.

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