The Drug Shortage Wars | The Health Care Blog (ovarian cancer untreated for weeks)

The Drug Shortage Wars | The Health Care Blog

The Drug Shortage Wars

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By Sanjay Bansu, MD

“I should have gotten cancer last month,” she told me.

That was the first thought from my patient after she’d heard the news: her ovarian cancer would remain untreated for weeks, due to a critical shortage of the chemotherapy agent doxorubicin. Like her, several thousand patients have been affected by critical shortages of chemotherapy agents like doxorubicin (Doxil) and methotrexate—common medicines that are essential backbones of cancer chemotherapy. But hundreds of other people have also been affected by critical shortages of pills around the country—limiting the supply of critical ICU medications like intravenous versed, or tuberculosis drugs like isoniazid.

Why are these shortages happening, and what can be done about them?....

 Related Posts

worth reading: Lessons for journalists & the public about medical conference news

 Blogger's Note: this is worth reading mostly in particular to the reading of published abstracts and the ultimate findings/abstract accuracy

 

Lessons for journalists & the public about medical conference news

Abstract - Biotargets of Cancer in Current Clinical Practice - Ovarian Cancer

 Medicine

Biotargets of Cancer in Current Clinical Practice

Current Clinical Pathology, 2012, 381-401, DOI: 10.1007/978-1-61779-615-9_14

Abstract -
  
Abstract

Ovarian cancer is the fifth most common cancer in women and is the most lethal of all gynecologic cancers. Early-stage ovarian cancer is curable while women who are diagnosed with advanced ovarian cancer continue to have poor long-term survival due to recurrence of disease. Unfortunately, most women are diagnosed with advanced-stage disease. Early detection is a primary objective for clinicians and scientists, yet single modality (CA-125, transvaginal ultrasound) screening tests have been ineffective. More recent novel approaches combining modalities and utilizing serial serum sampling are being tested and hold great promise. In addition, the recent application of proteomics to this clinical question has the potential to identify new and important biotargets.

Unfortunately, the majority of ovarian cancer patients have advanced-stage disease, and although most will die of their disease, their survival is quite heterogenous (different). 

The ability to stratify patients according to prognosis could help guide therapy. The current “gold standard” for prognosis uses patient, surgical, and tumor characteristics, yet these have the tendency to be notoriously inaccurate. This prognostic uncertainty and the drive to identify predictive factors by which we can select novel and targeted therapy have stimulated researchers to look beyond traditional markers and test and validate molecular and genomic biomarkers, which are anticipated to soon complement or even eclipse traditional factors clarifying prognosis and select treatments. 

For patients with advanced-stage disease, a multitude of prognostic factors have been characterized. While promising, none of these biotargets have been validated at present to be clinically useful. More recent application of genomic technologies is likely to yield clinically relevant signatures and/or biotargets which will provide the basis for personalization of care for these patients.

Cochrane Review: abstract/plain text summary - Centralisation of services for gynaecological cancer - The Cochrane Library - Woo - Wiley Online Library

Centralisation of services for gynaecological cancer - The Cochrane Library 

Authors' conclusions

We found low quality, but consistent evidence to suggest that women with gynaecological cancer who received treatment in specialised centres had longer survival than those managed elsewhere. The evidence was stronger for ovarian cancer than for other gynaecological cancers.
Further studies of survival are needed, with more robust designs than retrospective observational studies. Research should also assess the quality of life associated with centralisation of gynaecological cancer care. Most of the available evidence addresses ovarian cancer in developed countries; future studies should be extended to other gynaecological cancers within different healthcare systems.

 

Plain language summary

Gynaecological cancers are cancers affecting the ovaries, uterus, cervix, vulva, and vagina.  They are the second most common cancers among women, after breast cancer. It is often suggested that outcomes are improved by centralising care within highly specialised services that include expert surgeons, radiologists, pathologists, oncologists who specialise in chemotherapy and radiotherapy, specialist nurses and other health professionals. However, consensus is lacking on whether centralisation of care for gynaecological cancer helps patients to live longer. This review investigated this issue by comparing the survival of women diagnosed with gynaecological cancer who received care from specialised and unspecialised centres.

We used a set of tests to ensure that the evidence the five studies identified reached the quality standard for our analysis.The analysis of three studies combined (meta-analysis), assessing over 9000 women, suggested that institutions with gynaecologic oncologists (specialists in the field of gynaecological cancer treatment) on site may prolong the lives of women with ovarian cancer compared to community or general hospitals. Similarly, another meta-analysis of three studies which assessed well over 50,000 women, found evidence to suggest that teaching centres or regional cancer centres (specialised centres) (Blogger's Note: do the specialized/regional centre have gynecologic oncologists/clinical trial access....) may prolong the lives of women with gynaecological cancer compared to community or general hospitals. The largest study in this meta-analysis assessed all gynaecological cancers in 48,981 women, so it had major influence on the final result; this means that our findings are likely to be relevant to other gynaecological cancers, besides ovarian cancer.

Overall, the findings suggest that centralisation of care may prolong the lives of women with gynaecological cancer, and in particular ovarian cancer. However, the results should be interpreted with caution as all of the studies included in the review could be biased. For example, it is possible that the patients who were treated in specialised centres were less ill to begin with. Another weakness of the review is that only one of the studies included women with gynaecological cancers other than ovarian cancer. (Blogger's opinion: any studies of this nature should differentiate and isolate/categorize the gynecologic cancers as treatments, side effects, survival rates, genetics....vary greatly)

Ideally, further studies in this area are needed.  New studies should be designed to avoid the possibility of bias due to the treatment of women at specialist and non-specialist centres being systematically different.

Additionally, studies should assess the impact of centralisation of care on the quality of life of patients.

Most of the available evidence was about ovarian cancer in developed countries; future studies should be extended to other gynaecological cancers and to less developed countries.

Ontario (Canada) ombudsman could hold hospitals to account - thestar.com

Ontario ombudsman could hold hospitals to account - thestar.com

"Ontario is also the only province whose ombudsman cannot investigate hospitals and long-term care facilities."

abstract: Multidrug Resistance-Linked Gene Signature Predicts Overall Survival of Patients With Primary Ovarian Serous Carcinoma

Multidrug Resistance-Linked Gene Signature Predicts Overall Survival of Patients With Primary Ovarian Serous Carcinoma

Abstract

Purpose: 

This study assesses the ability of multidrug resistance (MDR)-associated gene expression patterns to predict survival in patients with newly diagnosed carcinoma of the ovary. The scope of this research differs substantially from that of previous reports, as a very large set of genes was evaluated whose expression has been shown to affect response to chemotherapy. 

Experimental Design: 

We applied a customized TaqMan Low Density Array, a highly sensitive and specific assay, to study the expression profiles of 380 MDR-linked genes in 80 tumor specimens collected at initial surgery to debulk primary serous carcinoma. The RNA expression profiles of these drug resistance genes were correlated with clinical outcomes. 

Results: 

Leave-one-out cross-validation was used to estimate the ability of MDR gene expression to predict survival. Although gene expression alone does not predict overall survival (P=0.06), four covariates (age, stage, CA125 level and surgical debulking) do (P=0.03). 

When gene expression was added to the covariates, we found an 11-gene signature that provides a major improvement in overall survival prediction (log-rank statistic P less than 0.003). The predictive power of this 11-gene signature was confirmed by dividing high and low risk patient groups, as defined by their clinical covariates, into four specific risk groups based on expression levels. 

Conclusion: 

This study reveals an 11-gene signature that allows a more precise prognosis for patients with serous cancer of the ovary treated with carboplatin- and paclitaxel-based therapy. These 11 new targets offer opportunities for new therapies to improve clinical outcome in ovarian cancer.

abstract: Adnexal masses in women with breast cancer

Adnexal masses in women with breast cancer:

Background

Adnexal masses detected in breast cancer survivors are of particular concern because of the increased risk of ovarian malignancy.

Aims

This study was performed to analyse adnexal masses among women with breast cancer with regard to variables predictive of malignancy.

Methods

The study included women with breast cancer who had undergone surgery for an adnexal mass between 2002 and 2010 at Hacettepe University Hospital. A total of 45 consecutive women with a mean age of 47.3 years (range 25–76) were analysed retrospectively.

Results

Of 45 cases reviewed, benign ovarian pathology was found in 35 cases (77.8%) and malignant ovarian neoplasms were found in 10 cases (22.2%). A simple ovarian cyst was observed in 25 cases (71.4%) as the most common type of benign pathology. Of the 10 cases with malignancy, 5 (50%) had primary ovarian carcinoma, while the remaining five women had breast carcinoma metastases to the ovary. Complex mass at ultrasonography, increased CA 125 level and oestrogen receptor–negative tumour were found to be the significant predictors of ovarian malignancy.

Conclusions

Although an adnexal mass in a woman with breast cancer is most commonly a benign ovarian cyst, the overall risk of ovarian malignancy is increased with breast cancer. An adnexal mass with complex architecture detected by ultrasonography and high CA 125 level were the strongest risk factors associated with increased risk of malignancy.

Optimizing Molecular-Targeted Therapies in Ovarian Cancer: The Renewed Surge of Interest in Ovarian Cancer Biomarkers and Cell Signaling Pathways : Table 1 (eg. HE4....)

Blogger's Note: the table includes biomarkers for ovarian cancer in research

Optimizing Molecular-Targeted Therapies in Ovarian Cancer: The Renewed Surge of Interest in Ovarian Cancer Biomarkers and Cell Signaling Pathways : Table 1

original article previously posted - link:
Journal of Oncology

abstract: Psychiatric morbidity in gynecological outpatients

Psychiatric morbidity in gynecological outpatients - Judd - 2012 - Journal of Obstetrics and Gynaecology Research

Abstract

Aim:  To assess the prevalence of depression and anxiety in women presenting with gynecological symptoms, to determine how many women with these disorders were receiving treatment for them, and to investigate risk factors for these disorders.

Method:  Two hundred and sixty-four women seeking medical care from gynecology clinics at a specialist women's hospital completed a self-report questionnaire asking about sociodemographics, physical and mental health, personality (neuroticism) and psychosocial stressors.

Results:  A total of 91 women met the diagnostic criteria for one or more Patient Health Questionnaire (PHQ) diagnosis. Forty-six (17.4%) met criteria for major depressive disorder (MDD), 15 (5.7%) for panic disorder (PD) and 73 (27.7%) for generalized anxiety disorder (GAD). Thirty-nine (42.9%) of the 91 women met criteria for two or more disorders. An additional 23 (8.7%) met DSM-IV-TR criteria for minor (sub-threshold) depression. Fifty percent with MDD, 4% with minor depression, 53% with PD and 22% with GAD reported they were receiving treatment. Psychosocial stressors and the neuroticism score were risk factors for both anxiety and depression.

Conclusions:  Anxiety and depression are common amongst women attending a gynecology clinic. Clinicians should be alert to the possibility of these disorders and make specific enquiries about their emotional wellbeing.

The Medicare NewsGroup introduces new website for journalists

The Medicare NewsGroup introduces new website for journalists

abstract: Evaluation of 2-Deoxy-2-[18F]Fluoro-D-glucose- and 3′-Deoxy-3′-[18F]Fluorothymidine–Positron Emission Tomography as Biomarkers of Therapy Response in Platinum-Resistant Ovarian Cancer

Molecular Imaging and Biology, Online First™ 

Abstract

Purpose  

We evaluated whether 2-deoxy-2-[¹⁸F]fluoro-D-glucose ([¹⁸F]FDG) and 3′-deoxy-3′-[¹⁸F]fluorothymidine ([¹⁸F]FLT) positron emission tomography (PET) could be used as imaging biomarkers of platinum resensitization in ovarian cancer.

Procedures  

Paired platinum-sensitive and platinum-resistant ovarian cancer cells from the same patient, PEO1 and PEO4, grown as tumor xenografts in nude mice, were assessed by PET.

Results  

The AKT inhibitor, API-2, resensitized platinum-resistant PEO4 tumors to cisplatin, leading to a markedly lower Ki67 labeling index (p ≤ 0.006, n = 6 per group). [¹⁸F]FDG-PET and [¹⁸F]FLT-PET imaging variables were lower after combination treatment compared with vehicle treatment (p ≤ 0.006, n = 6 per group). No changes were seen with either drug alone. PRAS40 phosphorylation status was a sensitive biochemical marker of pathway inhibition, whereas reductions thymidine kinase 1 expression defined the [¹⁸F]FLT response.

Conclusions  

Therapeutic inhibition of AKT activation in acquired platinum-resistant disease can be imaged noninvasively by [¹⁸F]FDG-PET and [¹⁸F]FLT-PET warranting further assessment. 

Seth's Blog: Is everyone entitled to their opinion?

Seth's Blog: Is everyone entitled to their opinion?

Is everyone entitled to their opinion?

Perhaps, but that doesn't mean we need to pay the slightest bit of attention.

There are two things that disqualify someone from being listened to:

1. Lack of Standing. If you are not a customer, a stakeholder or someone with significant leverage in spreading the word, we will ignore you. And we should.
When you walk up to an artist and tell her you don't like her painting style, you should probably be ignored. If you've never purchased expensive original art, don't own a gallery and don't write an influential column in ArtNews, then by all means, you must be ignored.
If you're working in Accounts Payable and you hate the company's new logo, the people who created it should and must ignore your opinion. It just doesn't matter to anyone but you.
I'm being deliberately harsh here for a reason. If we're going to do great work, it means that some people aren't going to like it. And if the people who don't like it don't have an impact on what happens to the work after it's complete, the only recourse of someone doing great work is to ignore their opinion.

2. No Credibility. An opinion needs to be based on experience and expertise. I know you don't like cilantro, but whether or not you like it is not extensible to the population at large. On the other hand, if you have a track record of matching the taste sensibility of my target market, then I very much want to hear what you think.
People with a history of bad judgment, people who are quick to jump to conclusions or believe in unicorns or who have limited experience in the market--these people are entitled to opinions, but it's not clear that the creator of the work needs to hear them. They've disqualified themselves because the method they use for forming opinions about how the market will respond is suspect. The scientific method works, and if you're willing to suspend it at will and just go with your angry gut, we don't need to hear from you.

If these two standards sound like precisely the opposite of what gets you on talk radio or active in anonymous chat rooms, you're right. Running your business or your campaign or your non-profit or your sports team based on what you hear on talk radio is nuts.

Blogger's Opinion: repost (2011) : Proteomic biomarkers in combination with CA 125 for detection of epithelial ovarian cancer using prediagnostic serum samples from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial - Moore - 2011 - Cancer - Wiley Online Library

Blogger's Note/Opinion:  
efforts to improve on the existing CA125 biomarkers remain elusive, as we speak;  this may be confirmed by the multitude of research studies/meta-analsyes (known issues); we, as patients/survivors, all have examples which are contrary, or exceptions,  to what is presently known and therefore the issue of 'personalized medicine'; biomarker banking (tissues from surgery for research) is an important key element for those diagnosed so that we may move forward beyond the standard CA125 (as one example); on the bonus side - research is moving forward at a greatly accelerated pace (molecular/proteomics...) but the research is still in the phase/s of being brought to the 'clinic',  meaning what actually works for our ovarian cancer women pre-present-post diagnosis; it is a common philosophy in ovarian cancer research that due to our low numbers (relative to other cancers) that we must have global research (not least of which is to mention global economics); as patients you can make a difference by ensuring that the clinical studies which you enroll will make a difference in these efforts as opposed to small isolated studies - specifically those that continue to regurgitate past studies which do not move forward beyond the existing eg. psychosocial aspects of prophlactic surgery


Proteomic biomarkers in combination with CA 125 for detection of epithelial ovarian cancer using prediagnostic serum samples from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial - Moore - 2011 - Cancer

RESULTS (abstract):

"CA 125 levels were elevated (≥35 U/mL) in 61.5% of 65 patients who had CA 125 data available from samples that were collected <12 months before cancer diagnosis; however, levels of the additional 7 biomarkers were not different between cases and the 3 control groups individually or combined. Two panels that combined CA 125 and the 7 biomarkers failed to improve the sensitivity of CA 125 alone."

DISCUSSION

 ".....Although a marginally better performance was observed for the identification of cases at least 6 months before diagnosis using an all-site multimarker panel (which included CA 125, HE4, tumor-associated glycoprotein 72 [CA 72-4], substance P-like immunoreactivity, andβ2M) were observed compared with CA 125 alone, the increase was not statistically significant.²¹ In addition to the current study, 5 additional panels were evaluated, none of which improved on the results with CA 125 alone.8 Considering the failure of multiple biomarkers to improve upon CA 125 in prediagnostic samples, new approaches are badly needed for biomarker discovery. One weakness of the current study is that we were unable to evaluate markers in nonwhite populations because of a very small number of nonwhite cases in the PLCO trial. The results of this combined effort will likely reshape our approach to biomarker discovery and validation. In addition to searching for protein analytes, autoantibodies also may be sought. Finally, previous studies have had limited success in identifying and evaluated autoantibodies of human proteins expressed in bacteria or insect cells. Recent advances in expressing human proteins in human cells could allow the identification of new epitopes that are selective for altered tertiary structure and glycosylation status of selected protein targets."