news: California Pacific Medical Center Shows New Strategy for Treating Ovarian Cancer Provides Survival Benefits with Fewer Side Effects

press release

 The open-label, phase 3 randomized study was conducted by researchers at Sutter Health’s California Pacific Medical Center (CPMC) and leading cancer centers across the U.S., and suggests new strategies for personalized treatments.

 “No previous studies assessed the weekly administration of paclitaxel with bevacizumab, to target angiogenesis,” said Dr. Chan. “Moreover, there has been little research into how taxanes may have differing effects depending on the concurrent administration of bevacizumab.”

 In the study, 692 women with newly diagnosed stage II-IV epithelial ovarian, fallopian tube, or primary peritoneal cancer who had received no prior treatment were prospectively stratified by whether they elected to receive bevacizumab, and then randomly allocated to receive either paclitaxel every three weeks plus carboplatin, or weekly paclitaxel plus carboplatin. The primary study endpoint was PFS.

OC Patient to Gyn Onc: "I am going to Canada for lunch!" - pic Ovarian Cancer Get Together (Whitby)

Missing:    Yi, Cora, Cathy, Monique, Dianna, Janet, Pam, Sandi

Where Are We 10 Years After the Women's Health Initiative?

Abstract

"The media attention surrounding the publication of the initial results of WHI in 2002 led to fear and confusion regarding the use of hormonal therapy (HT) after menopause. This led to a dramatic reduction in prescriptions for HT in the United States and around the world. Although in 2002 it was stated that the results pertained to all women receiving HT, subsequent studies from the Women's Health Initiative (WHI) and others clearly showed that younger women and those close to menopause had a very beneficial risk-to-benefit ratio. Indeed, the results showed similar protective effects for coronary disease and a reduction in mortality that had been shown in earlier observational studies, which had also focused on younger symptomatic women. In younger women, the increased number of cases of venous thrombosis and ischemic stroke was low, rendering them “rare” events using World Health Organization nomenclature. Breast cancer rates were also low and were found to be decreased with estrogen alone. In women receiving estrogen and progestogen for the first time in the WHI, breast cancer rates did not increase significantly for 7 years. Other data suggest that other regimens and the use of other progestogens may also be safer. It has been argued that in the 10 years since WHI, many women have been denied HT, including those with severe symptoms, and that this has significantly disadvantaged a generation of women. Some reports have also suggested an increased rate of osteoporotic fractures since the WHI. Therefore, the question is posed as to whether we have now come full circle in our understanding of the use of HT in younger women. Although it is appropriate to treat women with symptoms at the onset of menopause, because there is no proven therapy for primary prevention, in some women the use of HT for this role may at least be entertained."

paywalled: Nanocarrier systems for delivery of siRNA to ovarian cancer tissues, Expert Opinion on Drug Delivery

Nanocarrier systems for delivery of siRNA to ovarian cancer tissues, Expert Opinion on Drug Delivery

Expert opinion: Gene silencing therapy based on siRNA represents a possible opportunity for treatment of ovarian cancer patients. However, this approach requires selection of suitable nanocarriers that can safely and effectively deliver siRNA to the target site to induce its effect. Very little work has been done in this field; therefore, it is a good direction for future development.

paywalled: Intrapleural paclitaxel for malignant pleural effusion from ovarian and breast cancer: a phase II study with pharmacokinetic analysis.

Intrapleural paclitaxel for malig... [Cancer Chemother Pharmacol. 2012] - PubMed - NCBI
 

Intrapleural paclitaxel for malignant pleural effusion from ovarian and breast cancer: a phase II study with pharmacokinetic analysis.

Abstract

INTRODUCTION:

Malignant pleural effusion (MPE) is a frequent complication in many types of tumors diminishing the patient's ability to perform activities. Despite various studies on talc treatment, some doubts about its safety and effectiveness remain, so the search for a more ideal intrapleural agent continues. We analyzed the effectiveness and safety of intrapleural paclitaxel in ovarian and breast cancer patients.

CONCLUSION:

Intrapleural paclitaxel is a safe and effective palliative treatment for MPE from breast and ovarian cancers and may be integrated with systemic chemotherapy.

paywalled: Breast-feeding and risk of epithelial ovarian cancer (clear cell/endometrioid)

Breast-feeding and risk of epithelial ovarian cancer

 Abstract

PURPOSE:

Evidence suggests that breast-feeding may decrease the risk of epithelial ovarian cancer but it is not clear whether there is a relationship with duration of breast-feeding, patterns of breast-feeding, or particular histological subtypes of ovarian cancer. We sought to investigate these issues in detail.

METHODS:

Data from participants in a population-based study of ovarian cancer in western Washington State, USA (2002-2007) who had had at least one birth (881 cases and 1,345 controls) were used to assess relations between patterns of breast-feeding and ovarian cancer. Logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI).

RESULTS:

Women who ever breast-fed had a 22 % reduction in risk of ovarian cancer compared with those who never breast-fed (OR = 0.78, 95% CI 0.64-0.96) and risk reduction appeared greater with longer durations of feeding per child breast-fed (OR = 0.56, 95% CI 0.32-0.98 for 18 months average duration breast-feeding versus none). Introduction of supplementary feeds did not substantially alter these effects. The overall risk reduction appeared greatest for the endometrioid and clear cell subtypes (OR per month of average breast-feeding per child breast-fed = 0.944, 95% CI 0.903-0.987).

CONCLUSIONS:

Among women who have had the opportunity to breast-feed, ever breast-feeding and increasing durations of episodes of breast-feeding for each breast-fed child are associated with a decrease in the risk of ovarian cancer independent of numbers of births, which may be strongest for the endometrioid subtype.

Medscape: Ovarian Cancer Clinical Presentation - overview including symptoms

Ovarian Cancer Clinical Presentation

Aprl 5th, 2012: Who Gets Ovarian Cancer? | Mayo Clinic Podcasts

Who Gets Ovarian Cancer? | Mayo Clinic Podcasts

Mayo Clinic Podcasts

Medical and Health Podcasts from Mayo Clinic

← Do I Need a Hearing Aid?

Who Gets Ovarian Cancer?

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Posted on April 5, 2012 by mayoclinic

When it comes to ovarian cancer, are you at risk?  In this Medical Edge Radio episode, Mayo Clinic Dr. Paul Haluska provides some insight.
To listen, click the link below.
Who Gets Ovarian Cancer

abstract: Recent advances in drug delivery strategies for treatment of ovarian cancer, Expert Opinion on Drug Delivery, Informa Healthcare

Recent advances in drug delivery strategies for treatment of ovarian cancer, Expert Opinion on Drug Delivery

Introduction: Ovarian cancer is associated with the highest mortality rate of all gynecological malignancies, due in part to inadequate treatment strategies and the asymptomatic nature of the disease. Current standard of care includes surgery and systemic chemotherapy. However, this approach can result in toxicities and eventual disease relapse, due to the emergence of multidrug resistance. Drug delivery systems (DDS) have shown promise in overcoming many of the limitations facing conventional treatment regimens.

Areas covered: This review provides an overview of recent advances in DDS strategies for the treatment ovarian cancers. Nano-sized systems, including nanoparticles, micelles, liposomes and drug conjugates; microspheres; implants and injectable depots are discussed. The advantages, limitations and clinical potential of these strategies are also outlined.

Expert opinion: Nano-sized DDS enable passive targeting to tumors due to their size, and further improvements in tumor localization can be made using targeting moieties. Microspheres, implants and injectable depots have been investigated for peritoneal localized and sustained therapy. Overall, the benefits of using DDS for ovarian cancer therapy include higher drug levels at the diseased site, circumvention of drug resistance mechanisms, minimization of non-specific toxicities, improvements in solubility of poorly soluble drugs and elimination of toxicities associated with conventionally used pharmaceutical excipients.

UK media: Charity calls for ovarian cancer awareness campaign (one percent aware of ovarian cancer symptoms)

"ONLY one per cent of women in the East of England are very confident in noticing symptoms of ovarian cancer, and a leading charity says symptom awareness could prevent needless deaths.....".

"The Target Ovarian Cancer Pathfinder Study 2012 did find the number of women who recognised bloating as a major sympton has nearly doubled from nine per cent to 17 per cent, but in the East of England this was 13 per cent.

The charity said this still compares poorly to other cancers with 76 per cent of women knowing a breast lump is a sign of breast cancer.
Ms Jones said: “The evidence is piling up. Women are being let down by the failure to act in the UK. We need a national awareness campaign now to end needless deaths from this disease......"

The Clearity Foundation - Improving Treatment Options For Ovarian Cancer Patients

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open access: PLoS ONE: BRCAness Profile of Sporadic Ovarian Cancer Predicts Disease Recurrence

Background

The consequences of defective homologous recombination (HR) are not understood in sporadic ovarian cancer, nor have the potential role of HR proteins other than BRCA1 and BRCA2 been clearly defined. However, it is clear that defects in HR and other DNA repair pathways are important to the effectiveness of current therapies. We hypothesize that a subset of sporadic ovarian carcinomas may harbor anomalies in HR pathways, and that a BRCAness profile (defects in HR or other DNA repair pathways) could influence response rate and survival after treatment with platinum drugs. Clinical availability of a BRCAness profile in patients and/or tumors should improve treatment outcomes.

Objective

To define the BRCAness profile of sporadic ovarian carcinoma and determine whether BRCA1, PARP, FANCD2, PTEN, H2AX, ATM, and P53 protein expression correlates with response to treatment, disease recurrence, and recurrence-free survival.

Results

High PARP, FANCD2 and BRCA1 expressions were significantly correlated with each other; however, elevated p53 expression was associated only with high PARP and FANCD2. Of all patients, 9% recurred within the first year. Among early recurring patients, 41% had high levels of PARP, FANCD2 and P53, compared to 19.5% of patients without early recurrence (p = 0.04). Women with high levels of PARP, FANCD2 and/or P53 had first year cumulative cancer incidence of 17% compared with 7% for the other groups (P = 0.03).

Conclusions

Patients with concomitantly high levels of PARP, FANCD2 and P53 protein expression are at increased risk of early ovarian cancer recurrence and platinum resistance.

abstract: Clinicopathologic Characteristics and Survival in BRCA1- and BRCA2-Related Adnexal Cancer: Are They Different?

Abstract

Objective:  

Our aim was to examine the clinicopathologic characteristics and survival of ovarian, tubal, and peritoneal (further denoted "adnexal") cancer in BRCA1 compared with BRCA2 carriers.

Methods: A consecutive series of adnexal cancers in BRCA1/2 mutation carriers diagnosed in 1980 to 2010 at the University Medical Center Groningen was analyzed.

Results: 

We evaluated 55 BRCA1- and 16 BRCA2-related adnexal cancers, consisting of 51 ovarian, 13 tubal, and 7 peritoneal cancers. Peritoneal cancer was restricted to BRCA1 carriers. Ovarian and tubal cancer was equally present in both carrier groups. Median age at diagnosis was younger in BRCA1 compared with BRCA2 carriers (50 vs 54 years; P = 0.03). No other clinicopathologic differences were found. Regarding survival, a nonsignificant trend was noted for BRCA2 carriers to have fewer relapses, a longer time to first relapse, and a longer disease-free and overall survival.

Conclusions: Except for age at diagnosis and prevalence of peritoneal cancer, no significant clinicopathologic differences were found between BRCA1- versus BRCA2-associated adnexal cancer. On survival, it might be suggested that BRCA2 carriers have a more favorable outcome than BRCA1 carriers, marked by fewer relapses, a longer time to first relapse, and a longer disease-free and overall survival.

open access: 2011 Progression-free survival in advanced ovarian cancer: a Canadian review and expert panel perspective | Dr A. Oza | Current Oncology (topics: eg chronic disease, 1st line therapy...)

Blogger's Note: may require registration (free); note also list of useful (international) reference papers

                                                                                        


Ovarian cancer is leading cause of gynecologic cancer mortality in Canada. To date, overall survival ( os ) has been the most-used endpoint in oncology trials because of its relevance and objectivity. However, as a result of various factors, including the pattern of sequential salvage (outdated term)  therapies, measurement of os and collection of os data are becoming particularly challenging. Phase ii and iii trials have therefore adopted progression-free survival ( pfs ) as a more convenient surrogate endpoint; however, the clinical significance of pfs remains unclear. This position paper presents discussion topics and findings from a pan-Canadian meeting of experts that set out to

• evaluate the relevance of pfs as a valid endpoint in ovarian cancer;
• reach a Canadian consensus on the relevance of pfs in ovarian cancer; and
• try to address how pfs translates into clinical benefit in ovarian cancer.
  
  
  ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

Recommendations for future investigations include these:

• Ensure that trials are designed to evaluate pfs , os , and other clinically relevant endpoints such as disease-related symptoms or qol .
• Incorporate interim futility analyses intended to stop accrual early when the experimental regimen is not active.
• Stop trials early to declare superiority only when compelling evidence suggests that a new treatment provides benefit for a pre-specified clinically relevant endpoint such as os or symptom relief.
• Importantly, discourage early release of secondary endpoint results when such a release might increase the frequency of crossover to the experimental intervention.

abstract: Percutaneous Insertion of (IP) Peritoneal Ports (study = 29 women)

Objective: To describe a technique for image-guided percutaneous insertion of peritoneal ports in patients without ascites who have undergone surgical debulking for stage III ovarian cancer.

Conclusions: Placement of percutaneous intraperitoneal ports is feasible with an acceptably low complication rate of 6.9% in patients without abdominal ascites.

abstract: Significance of Perioperative Infection in Survival of Patients With Ovarian Cancer

Objectives:
Perioperative infectious diseases comprise some of the most common causes of surgical mortality in women with ovarian cancer. This study was aimed to evaluate the significance of perioperative infections in survival of patients with ovarian cancer.

Conclusion:

Perioperative infectious disease comprises an independent risk factor for survival of patients with ovarian cancer.

"Perioperative infections were associated with increased surgical mortality, delay in chemotherapy treatment, decreased chemotherapy response, shorter progression-free survival) and decreased overall survival ." (Blogger's note - stats removed for ease of reading)

abstract: Extraperitoneal metastases from recurrent ovarian cancer. (study n=233 women) eg. lung, CNS, pulmonary, skin (cutaneous)

Blogger's note: requires subscription ($$$) for full text

OBJECTIVES:

To identify patterns of metastasis in patients with recurrent ovarian cancer. The influence of the route of chemotherapy administration and sequence of agents on those patterns is also examined.

RESULTS:

Thirty-five subjects developed extraperitoneal recurrent ovarian cancer, with 26 subjects (74%) after IP treatment, and 9 subjects (26%) after IV treatment. Of these extraperitoneal recurrences, 26 were in the thoracic/pulmonary cavity, 7 were within the central nervous system (CNS), and 2 were in the cutaneous (skin) tissues. The CNS and cutaneous lesions were secondary recurrences, and all occurred in subjects who had initially received IP cisplatin/paclitaxel followed by IV BEV for recurrent disease.

CONCLUSIONS:

Extraperitoneal recurrences were more common in women treated with IP chemotherapy for ovarian cancer. Specifically, women treated with IV BEV as secondary therapy after IP were at particularly high risk of extraperitoneal metastases, including in the CNS and cutaneous tissues. Physicians should be aware of the possibility of unusual metastases after the combination of IP chemotherapy and BEV, and future prospective studies of this population should carefully evaluate recurrence site patterns.

Commentary to article Gilbert (Dove Project) - Early detection of ovarian cancer in symptomatic women : The Lancet Oncology

The Lancet Oncology, Early Online Publication, 17 January 2012

doi:10.1016/S1470-2045(11)70405-3

Early detection of ovarian cancer in symptomatic women

JR van Nagell a

"Since Goff and co-workers1 first reported that many women with ovarian cancer have symptoms of abdominal bloating, early satiety, pelvic pain, and urinary urgency, frequency, or both, questions have arisen as to whether assessment of these symptoms could lead to earlier detection of this cancer. The Diagnosing Ovarian Cancer Early (DOvE) pilot project reported in The Lancet Oncology by Gilbert and co-workers2 seeks to answer this question. Clinical examination, measurement of CA-125 concentrations in serum, and transvaginal ultrasonography (TVUS) were used in 1455 women older than 50 years who had symptoms associated with ovarian cancer. 11 ovarian cancers were detected, which yielded a prevalence of one per 132 women (0·76%), or about ten times that observed in screening studies in the USA, UK, and Japan.3—5."

"Whether assessment of symptomatic women with multiple methods will lead to detection at earlier stages or increase survival needs to be tested in larger numbers of cases. That the assessment algorithm used in the DOvE project identified most patients with symptomatic ovarian cancer when their disease was still resectable, however, is encouraging. Optimum cytoreduction is associated with a notable survival advantage in patients with ovarian cancer, and was achieved in eight (73%) of 11 women in the study group versus 33 (44%) of 75 women in a control group of patients with ovarian cancer who had been referred to a local gynaecological oncology clinic (p=0·075). The degree of cytoreduction, however, also depends on factors other than tumour burden, including the location of disease and experience of the surgeon. To continue this project beyond the pilot phase, it will be important to document disease substage and note tumour volume before debulking (in study and control cases) to establish whether assessment-driven interventions affect tumour burden. Although the DOvE algorithm successfully identified 11 cases of ovarian cancer, 1444 (99.2%) symptomatic women did not have ovarian cancer. In the next phase of this study, the positive and negative predictive values of each symptom must be critically assessed to identify the profile of highest risk. Additionally, the duration of symptoms before ovarian cancer detection should be recorded for the study and control populations. In this way, it should be possible to investigate whether a public education campaign alters the time from symptom onset to detection of disease in patients with ovarian cancer."
..................................................................................................................

Assessment of symptomatic women for early diagnosis of ovarian cancer: results from the prospective DOvE pilot project

Prof Lucy Gilbert MD et al

open access: JNCI - Predicting the Value of Indexing Symptoms for Ovarian Cancer

open access - JNCI: Finding Ovarian Cancer (correspondence in response to Lim et al.)

"For decades, investigators have sought a strategy for finding ovarian cancer early enough to reduce the risk of dying of ovarian cancer. In this issue of the Journal, Lim et al. (1) report on their study in which women answered a dozen simple questions such as whether they felt pelvic or abdominal pain in the recent past and, if so, when, how frequently, and how severely. Symptom indices like this are being promoted as easier or better ways to find ovarian cancer early, under the assumption that early therapy can achieve a better outcome than if the women wait until more or worse symptoms prompt them to see a physician. The study revealed that symptom indices as ovarian cancer screeners can be sensitive to the presence of cancer in the period between 3 and 14 months before clinical diagnosis......