Ovarian Cancer

While 90% of cancers occur as a result of factors related to lifestyle, the environment, or aging, 5% to 10% of cancers are passed down from generation to generation. Breast cancer is the most common cancer diagnosis in American women.

Epithelial ovarian cancer (EOC) spreads prominently within the peritoneal cavity. In fact, we now know that high-grade serous cancers are often of tubal origin, and their presentation as tubo-ovarian masses renders it likely that intraperitoneal spread occurs as an early event in their clinical evolution.

"Kinome" is the word to know this year in oncology, because it has begun to reveal molecules that some tumors are relying on to survive, which until now we had no idea were involved in cancer or which we hardly knew at all.

Early results from the ICON7 trial suggest that adding bevacizumab (Avastin) to standard chemotherapy in women with newly diagnosed ovarian cancer reduces the risk of disease progression during the first year of treatment.

For women with triple-negative breast cancer, BRCA mutations can be a boon: These patients have a significantly lower risk of relapse than their counterparts who do not carry BRCA mutations, according to a study out of Houston’s M.D. Anderson Cancer Center. SABCS 2010 will feature an education session on the clinical utility of genetic testing for inherited predisposition to breast cancer.

The search for a magic bullet against cancer historically has glowed bright then dimmed, depending on the stage of discovery. Developments surrounding monoclonal antibodies and angiogenesis inhibitors have followed this cycle, as exuberance for their potential has bowed to the nuances that underlie the complex mechanisms on which they depend.

Aetna is examining data from 13,000 of its members to determine if patients who should be getting breast-and-ovarian cancer screening tests are in fact being offered them.

An advisory panel recommended revoking bevacizumab’s approval in breast cancer. Oncologists and patients express concern about what the future holds for those who do benefit from bevacizumab.

Patient preference needs to be weighed against overall societal benefits.

As outlined in the excellent, comprehensive review by Drs. Liu and Matulonis, ovarian cancer is the most lethal gynecologic malignancy in the United States, with approximately 16,000 deaths and 22,000 new cases yearly.[1] The vast majority of patients present with intra-abdominal spread of disease at the time of diagnosis, resulting in low overall cure rates. As outlined, patients are primarily managed with primary surgical resection and subsequent platinum-based chemotherapy.

Epithelial ovarian cancer is the leading cause of death from gynecologic malignancy in the United States, with approximately 15,000 deaths per year. Platinum/taxane doublets have long been considered the standard treatment regimen for advanced-stage disease; however, recent studies have sought to improve on the outcome from this therapy. Intraperitoneal (IP) chemotherapy has been shown to yield superior progression-free survival (PFS) and overall survival (OS); however, logistical problems and toxicities have limited more widespread adoption. Recent studies have also suggested that a “dose-dense” schedule of paclitaxel in combination with carboplatin may result in improved outcomes, and the impact of biological therapies in the first-line setting is under active investigation. In the setting of recurrent disease, preliminary results suggest that novel doublet regimens such as carboplatin and pegylated liposomal doxorubicin may have similar activity to standard platinum/taxane doublets while carrying a reduced risk of allergic reactions. Additionally, targeted therapy remains an active area of investigation, with evidence of activity from agents such as PARP inhibitors, anti-angiogenics, and PI3 kinase inhibitors. Here, we review recent advances in our understanding of ovarian cancer and its treatment in both the newly diagnosed and recurrent settings.

After years of maintaining the status quo in ovarian cancer treatment, a number of recent advances have challenged the paradigm based on intravenous (IV) taxane and platinum as the therapy of choice for advanced ovarian cancer. These new data are summarized concisely by Liu and Matulonis in this issue.

Once thought a risk for malignancy, septated ovarian cystic tumors are actually mostly benign. A study at the University of Kentucky changes the standard of care for those patients.

Citing different studies, two physicians reach different conclusions as to whether ovarian cancer screening is worthwhile.

Mrs. S. is a 37-year-old Caucasian female who sought care at her home institution overseas during a period of several months for complaints of esophageal reflux, constipation, early satiety, increasing abdominal girth, and fatigue.

Postmenopausal women at average risk of ovarian cancer may benefit from ROCA (Risk of Ovarian Cancer Algorithm), a new ovarian cancer screening strategy that combines information about trends in CA-125 blood test results and age, followed by transvaginal ultrasound (TVU) as needed and referral to a gynecologic oncologist. Results of a prospective multicenter trial of ROCA were reported at the 44th annual meeting of ASCO (abstract 5003). Results of ROCA testing were used to categorize women as low risk (requiring a repeat CA-125 test in 1 year); intermediate risk (repeat CA-125 test in 3 months); or high risk (TVU and referral to a gynecologic oncologist, who decides, based on clinical findings and the TVU result, whether the patient needs to undergo surgery).

It can alleviate adverse effects of cancer treatment, but can it also be used as a chemopreventive?

Postmenopausal women who regularly use painkillers have lower estrogen levels, which could lead to a decreased risk of breast or ovarian cancer.

A weekly course of paclitaxel has proved itself effective in breast cancer and is feasible in ovarian cancer as well. But questions remain as to the actual benefits of a shorter treatment course.

Why doesn't cisplatin work very well against breast cancer? The first response of most researchers would be to invoke something about genetic responses, but a pair of biologists from the University of Cincinnati have raised a quite different proposalr: The unique hormonal milieu of the breast may contribute to chemoresistance.

Malignant pleural effusion complicates the care of approximately 150,000 people in the United States each year. The pleural effusion is usually caused by a disturbance of the normal Starling forces regulating reabsorption of fluid in the pleural space, secondary to obstruction of mediastinal lymph nodes draining the parietal pleura.

Carcinoma of an unknown primary site is a common clinical syndrome, accounting for approximately 3% of all oncologic diagnoses. Patients in this group are heterogeneous, having a wide variety of clinical presentations and pathologic findings. A patient should be considered to have carcinoma of an unknown primary site when a tumor is detected at one or more metastatic sites, and routine evaluation (see below) fails to define a primary tumor site.

Genetic and genomic research is creating new and more individualized approaches to better manage a person's disease or predisposition to disease, including cancer.

Magnets have been thought for centuries to have healing power. Scientists at Georgia Institute of Technology and the Ovarian Cancer Institute hope to take this possibility a quantum leap further. They are grooming magnetic nanoparticles as the mainstay of a technique aimed at filtering out free-circulating ovarian cancer cells from the body. Their goal is to slow or stop the metastatic spread of cancer.

Pharmacologic strategies targeting the DNA of tumor cells have been in use for much of the past century for many different cancer types. Radiation has also been a long-employed strategy to cause DNA damage and subsequent tumor cell death. However, the class of agents designed to inhibit the enzyme poly-(ADP-ribose) polymerase (PARP) have taken this a step further-these agents do not damage DNA themselves, but rather, inhibit the repair of DNA via inhibition of the base excision single-strand repair pathway. PARP inhibitors have been shown preclinically and clinically to enhance the affects of chemotherapies known to damage DNA or interefere with DNA replication. However, the most exciting use of PARP inhibitors may be in exploiting the concept of synthetic lethality. In this setting, the concept is based on two factors: (1) BRCA1/2-positive malignancies cannot use one of the major pathways to repair double-strand DNA breaks (ie, homologous recombination), and (2) making the base excision repair pathway nonfunctional via inhibition of PARP leads to tumor cell death, as unrepaired single-strand breaks are converted into double-strand breaks.

While they represent a minority of patients with lung cancer, more than 20,000 people in the United States who never smoked cigarettes are diagnosed with lung cancer each year.[1] This makes lung cancer in “never-smokers” one of the 10 most common cancers-more common than ovarian cancer. In this issue of ONCOLOGY, Subramanian and Govindan give an overview of emerging data about lung cancer in never-smokers.[2] The data outlined in this review provide support for the hypothesis that we can define this collection of diseases affecting never-smokers not by the absence of a common risk factor (smoking) but by each tumor’s molecular features.

As knowledge increases about the processes underlying cancer, it is becoming feasible to design “targeted therapies” directed toward specific pathways that are critical to the genesis or maintenance of the malignant phenotype. Poly(ADP-ribose) polymerase (PARP) inhibitors are an example of this new framework. DNA damage repair is a complex and multifaceted process that is critical to cell survival. Members of the PARP family are central to specific DNA damage repair pathways, particularly the base excision repair (BER) pathway. PARP inhibition, with subsequent impairment of the BER mechanism, may enhance the cytotoxicity of agents that generate single-strand breaks in DNA, such as radiation and certain chemotherapy drugs. In addition, PARP inhibitors may induce death through “synthetic lethality” if the DNA repair mechanisms that rescue BER-deficient cells are themselves impaired. This mechanism is thought to underlie the impressive results of PARP inhibition in BRCA-associated breast and ovarian cancer, and may also account for the reported benefit of this approach in “triple-negative” breast cancer. This review will examine the current understanding of PARP inhibition as a treatment for breast cancer, ongoing clinical trials, and future directions for this new approach.

The American Society of Clinical Oncology (ASCO) released its report, Clinical Cancer Advances 2009: Major Research Advances in Cancer Treatment, Prevention and Screening, an independent assessment of the most significant clinical cancer research studies of the past year, including 15 major advances.

BELGRADE-Endocyte presented phase IIa data from its trial using EC145 (pegylated liposomal doxorubicin) in women with advanced-stage ovarian cancer at the 2009 European Society of Gynaecological Oncology.

The following company announcements were made at ECCO/ESMO 2009 in Berlin: Pfizer drugs prolong overall survival Pfizer Oncology released data from a phase III trial for sunitinib (Sutent) for the treatment of progressive,