Primary care physicians need to be better integrated into cancer survivor care

The American Society of Clinical Oncology (ASCO) recommends coordination of care for cancer survivors.  Primary care physicians, PCPs, according to ASCO are "often unfamiliar with the consequences of cancer and its treatment and seldom receive explicit survivor care guidance about potential treatment effects from oncologists" according to Dr. Melissa Hudson from the St. Jude Children's Research Hospital.  Dr. Hudson is an author of a recently published article in the Journal of Clinical Oncology.

In the article, there are recommendations for a risk-stratified approach to caring for the patient by the PCP based on a transition of care from the oncologist to the PCP.

Components of that plan might address:

• Increased risk for cardiovascular disease, diabetes, and other chronic disease

• Psychosocial needs

• Fertility planning for patients in their reproductive years

• Known persistent and late-occurring side effects of cancer and cancer treatment

• Screening guidelines and symptoms of recurrence or second primary cancers

• Lifestyle guidance

Arthritis related pain and safety concerns of NSAIDs

This month, the December 2012 issue of the Open Rheumatology Journal published an online article from a group that was brought together for a meeting in Aachen, Germany by Grünenthal GmbH, a pharmaceutical company.  The authors were compensated for their time and had assistance in the writing of the publication, which was funded by Grünenthal.

The article describes osteoarthritis and rheumatoid arthritis, as well as multiple therapies.  It concludes that the use of combinations of medications, as well as a multimechanistic approach are what is needed to help avoid the long-term potential safety concerns associated with NSAIDs. 

Inconsistency seen in safety labeling for generic drugs

An article published in  Pharmacoepidemiology and Drug Safety notes that over two-thirds of generic drugs in the U.S. have safety warning labels that differ from the equivalent brand-name medications.

According to the lead author, Jon Duke, "generic drug labels may contain incomplete or incorrect safety information."  This becomes problematic when the generic label is used by the physician to make prescribing decisions. If side effects, information on durg interactions or other safety issues are not in the label, then the patient may be at an increased risk for adverse events.

Out of more than 1,000 generic drugs, nearly 70% had some discrepancies in their safety labeling. Strikingly,  9% had differences of more than 10 side effects.

Androgen deprivation and prostate cancer

Saylor and Smith of the Massachusetts General Hospital Cancer Center in Boston, Massachusetts have an article that is coming out in the Journal of Urology in January 2013 which discusses adverse effects of androgen deprivation therapy (ADT).  Their review focuses on the more recently described metabolic complications of ADT including obesity, insulin resistance and lipid alterations as well as the association of androgen deprivation therapy with diabetes and cardiovascular disease.

They found that ADT causes a decrease in lean mass (muscle) and an increase in the mass of fat.  This was associated with a decrease in insulin sensitivity and increase in LDL, HDL and triglycerides.  This is associated with an increase in the incidence of diabetes and cardiovascular disease.

The benefit versus the risk of ADT must be considered when considering treatment, and it is recommended to screen for risk factors associated with diabetes and cardiovascular disease  and treat as indicated, thus mitigating the adverse effects that can be associated with ADT.

Mobile App for Oncology Adverse Events And Graft-Versus-Host Disease

Velos Aversi, an iPad app for clinicians in oncology and bone marrow transplantation has recently been released.

Velos Aversi is designed to record, track, and export patient adverse events (AE) and Graft-Versus-Host Disease (GVHD) at point-of-care in hospital and ambulatory care settings. With a few touches on the iPad, clinicians, physicians, and research nurses can review and manage their patients’ AE and GVHD histories anytime, anywhere—freeing them from large and cumbersome paper files. The app allows for more accurate attribution and reduces transcription errors that can occur when AE data entry is delayed. Direct and immediate input by clinicians saves time and ensures the quality of the record, particularly when grading events.

Antinausea Drug Withdrawn From US Market

The FDA announced that the 32 mg dose of Zofran (ondansetron), an anti-nausea medication, will no longer be marketed in the US due to the potential the risk of Torsades de pointes, a serious cardiac rhythm abnormality.  The event occurs when there is a prolongation in the QTc interval, an important part of the electrical activity of the heart.  Prolongation of the QTc can be fatal.  Information from the FDA can be found here.

Diet Drugs and Death

It has been known for quite awhile that drug-induced valvulopathy is an issue for fenfluramines (diet drugs).

Fenfluramine, which was sold as Pondimin, Ponderax and Adifax, was one part of a two drug combination sold as Fen-Phen for anti-obesity.  Fenfluramine was removed from the U.S. market in 1997 following reports of heart valve disease and pulmonary hypertension.    The other medication in the diet combination was phentermine.

Fenfluramine is a mixture of dextrofenfluramine and levofenfluramine (i.e. it's racemic mixture of two enantiomoers).  It causes an increase in the neurotransmitor serotonin.  Serotonin is known to be responsible for mood and appetite.  The increase in serotonin leads to the sensation of feeling full and not hungry.  It is postulated that fenfluramine, a sympathomimetic amine, causes release of serotonin and inhibits the reuptake of serotonin.  High levels of serotonin are found to decrease appetite in humans.

Fenfluramine, however, has "off-target" effects via activation of 5-hydroxytryptamine (5-HT) 2B receptor (5-HT2BR) expressed on heart valve leaflets.  This leads to a growth on the heart valves, leaving them structurally changed and incapable of closing properly.  Clinically, this can be detected by cardiovascular symptoms, which include a heart murmur, shortness of breath (dyspnea), edema, chest pain, congestive heart failure (CHF), palpitations, as well as supraventricular tachycardia. These symptoms are well described in the New England Journal of Medicine.

Macroscopic appearance: anterior leaflet 
of the mitral valve
 with thickened and retractile insertion 
of the chordae tendineae.

It is postulated that fenfluramine, a sympathomimetic amine, causes release of serotonin and inhibits the reuptake of serotonin.  As noted above, high levels of serotonin are found to decrease appetite in humans.  Elevated serotonin is also associated with acute or chronic pulmonary hypertension from pulmonary vasoconstriction or cardiac valve fibrosis (endocardial fibrosis) from overstimulation of serotonic growth receptors on fibrocytes.  Additionally increased serotonin levels are a factor in retroperitoneal fibrosis.

Serotonin is an intense pulmonary vasoconstrictor that stimulates proleferation of vascular smooth muscle by interacting synergistically with platelet-derived growth factor.