FDA U.S. Drug Shortages - Paclitaxel (Taxol)

Paclitaxel Injection (updated 3/2/2012)

Company/Products	Reason	Related Information
Sandoz: 1-800-525-8747 6 mg/mL injection 30 mg/5 mL vial (NDC 66578-0043-01) 100 mg/16.7 mL vial (NDC 66578-0043-02) 300 mg/50 mL vial (NDC 66578-0043-03)	Manufacturing delays	Sandoz is currently on backorder.
APP 1-888-386-1300 6 mg/mL injection 30 mg/5 mL vial (NDC 63323-0763-05) 100 mg/16.7 mL vial (NDC 63323-0763-16) 300 mg/50 mL vial (NDC 63323-0763-50)	Increase in demand	APP is on intermittent back order and is releasing product as it becomes available.
Hospira Inc. Customer Service: 1-877-946-7747 300 mg/50 mL vial (NDC 0409-0342-50) 30 mg/5 mL vial (NDC 0409-0342-09) 100 mg/16.7 mL vial (NDC 0409-0342-22)	Higher than anticipated market demand.	Product 30 mg/5 mL vial (NDC 0409-0342-09): ample levels of inventory to support market demand. Product 300 mg/50 mL vial (NDC 0409-0342-50): next delivery March. Product 100 mg/16.7 mL vial (NDC 0409-0342-22): next delivery April. Please check with your wholesaler for available inventory.
Bedford Laboratories 1-800-562-4797 6 mg/mL injection 30 mg/5 mL vial (NDC 55390-0114-05) 100 mg/16.7 mL vial (NDC 55390-0114-20) 300 mg/50 mL vial (NDC 55390-0114-50)	Manufacturing delays	Bedford has all paclitaxel presentations on backorder and the company cannot estimate a release date.
Teva 1-800-545-8800 6 mg/mL injection 30 mg/5 mL vial (NDC 00703-4764-01) 100 mg/16.7 mL vial (NDC 00703-4766-01) 150 mg/25 mL vial (NDC 00703-4767-01) 300 mg/50 mL vial (NDC 00703-4768-01)	Manufacturing delays	Teva continues to release Paclitaxel 30mg/5mL vial (NDC 00703-4764-01), Paclitaxel 100mg/16.7mL vial (NDC 00703-4766-01), Paclitaxel 150mg/25mL (NDC 00703-4767-01) and Paclitaxel 300mg/50mL (NDC 00703-4768-01) as it becomes available
Sagent Pharmaceticals 1-866-625-1618 30mg/5mL NDC 25021-213-05 100mg/16.7mL NDC 25021-213-17 300mg/50mL NDC 25021-213-50		Sagent has the 5mL and 16.7mL on allocation and the 50mL product is available.

The silent minority - unpublished data on cancer care - Impact Factor - Isseus 46 - Articles - Cancer World

The silent minority - unpublished data on cancer care

From 1989 to 2003, 709 phase III trials evaluating systemic cancer treatment were presented at ASCO meetings. Tam and collaborators have now reported that 9% of these trials were never published, and 13% were published after a five-year delay. More than half of these studies would have had clinical impact if published promptly.

» Daniel F. Hayes

Two key elements of the scientific method are methodology transparency and reproducibility of results by others. Traditionally, these elements have been facilitated by the well-entrenched system of peer-review publication. This concept has had almost universal acceptance among the scientific community, although in the past few years there have been calls for open publication of all scientific results without the peer-review process. Some experts have advocated the creation of a type of ‘free-for-all’ post-publication peer review, with the view that classic, pre-publication peer review is usually selective (based on whom the editor knows and on who actually agrees to referee the article) and arbitrary (based on the respective biases of the reviewers).[1]........

2012 Hormone Therapy Position Statement of the North American Menopause Society (PDF/repost)

POSITION STATEMENT The 2012 Hormone Therapy Position Statement of The North American Menopause Society

FDA: The Quality Problems Causing The Drug Shortage Were Not News To Those Making The Medicines - blog

Dr Len's Cancer Blog:

"Sometimes you have the opportunity to be educated, or to learn a bit more about a topic of importance. Yesterday was one of those opportunities.

Attending a meeting (as an observer) of the National Cancer Institute Director's Consumer Liaison Group on the issue of cancer drug shortages, there were some messages delivered that provided a bit more clarity surrounding a very complex problem. And there were messages delivered that had even me sit up and take notice, and frame the seriousness and depth of the problems that confront patients, their families and those who treat them. The observations were--to say the least--very unsettling.

Try this one, for example:......

[Comment] Offline: Is CDC a science-based organisation? The Lancet

[Comment] Offline: Is CDC a science-based organisation?:

"When we published our first report describing discontent about the work of the Center for Global Health (CGH) at the US Centers for Disease Control and Prevention, CDC immediately contacted us to ask for an opportunity to reply. We agreed and await their response. Meanwhile, two further letters have arrived. They again signal severe concerns about the way in which CDC organises its global health work. Both correspondents are well informed about the details of the CDC's work in global health. Their allegations are serious." (subscription required $$$)

media: Benefits of Bevacizumab in Ovarian Cancer Clarified - Michael J. Birrer, MD, PhD

"Bevacizumab (Avastin) has failed to demonstrate statistically significant improvements in overall survival (OS) for women with recurrent ovarian cancer in 2 recent clinical trials, but those results may be affected by factors not related to the drug’s efficacy, according to Michael J. Birrer, MD, PhD......

[Lancet Oncology News] US firm corners exclusive license for RAD51C cancer gene

[News] US firm corners exclusive license for RAD51C cancer gene:

"Already facing a legal challenge to its BRCA1 and BRCA2 patents, Myriad Genetics (Salt Lake City, UT, USA) has secured an exclusive licence for another breast and ovarian cancer-associated gene, RAD51C, under agreement with the German Consortium for Hereditary Breast and Ovarian Cancers, which will share exclusivity in Germany. RAD51C will be used to test patients' hereditary breast and ovarian cancer risks."

High-Risk Ovarian Cancer Based on 126-Gene Expression Signature Is Uniquely Characterized by Downregulation of Antigen Presentation Pathway - Japan

Abstract

Purpose: 

High-grade serous ovarian cancers are heterogeneous not only in terms of clinical outcome but also at the molecular level. Our aim was to establish a novel risk classification system based on a gene expression signature for predicting overall survival, leading to suggesting novel therapeutic strategies for high-risk patients. 

Experimental Design: 

In this large-scale cross-platform study of six microarray data sets consisting of 1,054 ovarian cancer patients, we developed a gene expression signature for predicting overall survival by applying elastic net and 10-fold cross-validation to a Japanese data set A (n = 260) and evaluated the signature in five other data sets. Subsequently, we investigated differences in the biological characteristics between high- and low-risk ovarian cancer groups. 

Results: 

An elastic net analysis identified a 126-gene expression signature for predicting overall survival in patients with ovarian cancer using the Japanese data set A (multivariate analysis, P = 4 × 10⁻²⁰).. ........ Through gene ontology and pathway analyses, we identified a significant reduction in expression of immune-response–related genes, especially on the antigen presentation pathway, in high-risk ovarian cancer patients. 

Conclusions: 

This risk classification based on the 126-gene expression signature is an accurate predictor of clinical outcome in patients with advanced stage high-grade serous ovarian cancer and has the potential to develop new therapeutic strategies for high-grade serous ovarian cancer patients. 

Phase I Study of the Vascular-Disrupting Agent OXi4503

Phase I Study of the Vascular-Disrupting Agent OXi4503:

Purpose:
Preclinical studies show that OXi4503 (combretastatin A1 diphosphate, CA1P) is more potent than other clinically evaluated vascular-disrupting agents.

Experimental Design:
Escalating doses of OXi4503 were given intravenously over 10 minutes on days 1, 8, and 15 every 28 days to patients with advanced solid tumors.

Results:
Doses were escalated in single-patient cohorts from 0.06 to 1.92 mg/m², then expanded cohorts to 15.4 mg/m² in 43 patients. Common adverse drug reactions were hypertension, tumor pain, anemia, lymphopenia, and easily controllable nausea/vomiting and fatigue. Five patients experienced different drug-related dose-limiting toxicities, atrial fibrillation, increased troponin, blurred vision, diplopia, and tumor lysis. Prophylactic amlodipine failed to prevent adverse events. Pharmacokinetics showed dose-dependent linear increases in peak plasma concentrations and area under the curve value of OXi4503. One partial response was seen in a heavily pretreated patient with ovarian cancer. Dynamic contrast-enhanced MRI confirmed a dose effect and showed significant antivascular effects in 10 of 13 patients treated at doses of 11 mg/m² or higher.

Conclusions:
The maximum tolerated dose was 8.5 mg/m² but escalation to 14 mg/m² was possible with only temporary reversible cerebrovascular toxicity by excluding hypertensive patients. As a tumor response was seen at 14 mg/m² and maximum tumor perfusion reductions were seen at doses of 11 mg/m² or higher, the recommended phase II dose is from 11 to 14 mg/m². Clin Cancer Res; 18(5); 1415–25. ©2012 AACR.

Amlodipine (Brand name: Norvasc)

www.nlm.nih.gov

Amlodipine is used alone or in combination with other medications to treat high blood pressure and chest pain (angina). Amlodipine is in a class of medications called calcium channel blockers. It lowers blood pressure by relaxing the blood vessels so the heart does not have to pump as hard. It controls chest pain ...

Side effects - How to take - Precautions - Dietary Instructions - Missed a dose

abstract: Histology-specific long-term trends in the incidence of ovarian cancer and borderline tumor in Japanese females: A population-based study from 1983 to 2007

 Blogger's Views:
there are a number of interesting subjects here - Japan appears historically to have a higher rate of clear cell than other nations; Japan has also studied clear cell ovarian cancer more extensively than elsewhere (for obvious reasons); increasing incidence rates observed in the Japanese population seems to be contrary to other nation's research (eg. stable/declining incidence rates) however the key is in the data compliation (eg. exclusion of LMP; peritoneal cancers), it can be noted however that there has been reported in the North America's that ovarian cancer rates have been increasing but for some unknown (or unpopular?) reason less is known about the reasons for these discrepancies; past blogs have been posted about increasing incident rates; it is unfortunate that this paper is not open access

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Histology-specific long-term trends in the incidence of ovarian cancer and borderline tumor in Japanese females: A population-based study from 1983 to 2007 in Niigata:

Abstract

Aim: 
The histology-specific long-term trends in the incidence of ovarian cancer and borderline tumors in Japanese women were examined, based on data from the population-based cancer registry in Niigata, Japan.

Material and Methods: 
Data were obtained from the Niigata Gynecological Cancer Registry, which covered the entire female population in Niigata prefecture, Japan, during the period from 1983 to 2007.

Results: 
A total of 3134 females with epithelial ovarian cancer, including borderline tumor cases, were diagnosed between 1983 and 2007. The age-standardized rates (ASRs) of both ovarian cancer and borderline tumors have steadily increased, with significant changes in ovarian cancer in all age groups, and borderline ovarian tumors in subjects aged <50. The ASRs of endometrioid adenocarcinoma showed a steady increasing trend, and those of clear cell and mucinous adenocarcinomas showed significant increasing trends in the total population. The ASRs of clear cell, mucinous, and endometrioid adenocarcinomas in the 50+ age group were significantly increased, especially the incidence of clear cell adenocarcinoma, which strikingly increased by approximately threefold from 1.2 (1983–1989) to 3.5 (2000–2007) per 100 000 females.

Conclusion: 
This prefecture-wide study showed the practical trends in ovarian cancer and borderline tumors in Japanese females. The incidence of ovarian cancer has steadily increased, with significant increases in the incidence of clear cell and mucinous adenocarcinomas in the total population during the past two decades. Because of the poor response rate of these histological subtypes to platinum-based regimens, novel treatment approaches should be adopted to improve the prognostic outcome in patients with ovarian cancer in Japan.

Bioinformatics and epigenetics - computer-aided cancer diagnosis - medical press

The relatively young research field of epigenetics is the talk of the town. Many scientists expect the research on biochemical modifications beyond the actual DNA strand to lead to huge progress in the understanding of the regulation of gene activity in the years to come. Just how promising the results of epigenetic research are in terms of concrete medical applications is demonstrated by the work of Thomas Lengauer and Christoph Bock from the Max Planck Institute for Informatics in Saarbrücken. With the help of computers, they trawl through the genomes of cancer patients in search for suspect structures, and develop fast and simple new tools for improving cancer diagnosis in hospitals.


"Although Thomas Lengauer regards epigenome analysis as playing a crucial role in the attainment of rapid progress in cancer diagnosis in the near future, he plays down expectations with regard to the development of new drugs. “Many scientists point to the potential of future drugs that can repair defects in the epigenome of diseased cells. I tend to be more cautious in this regard. Such targeted interventions involve significant risks, not least because little or nothing is currently known about the highly-complex gene regulation mechanisms being manipulated here.”"