NEW DRUGS
Perjeta, an Antibody
For Metastatic Breast Cancer
HER-2, a protein involved in normal cell
growth, is found in increased amounts
on some types of cancer cells, including
some breast cancers. In HER-2–positive
breast cancer, the increased amount of
the HER-2 protein contributes to cancer
cell growth and survival. About 20% of
breast cancers have increased amounts
of HER-2.
The FDA recently approved a new anti–
HER-2 therapy, pertuzumab (Perjeta,
Genentech), to treat patients with HER-2–
positive late-stage breast cancer. The drug
is intended for patients who have not been
treated for metastatic breast cancer with
an anti–HER-2 drug or chemotherapy.
Perjeta is combined with trastuzumab
(Herceptin, Genentech), another anti–
HER-2 agent, and docetaxel (Taxotere,
Sanofi), a type of chemotherapy.
Perjeta is a humanized monoclonal
antibody manufactured through biotechnology methods. Administered intravenously, it is believed to work by
targeting a different part of the HER
protein than is targeted by trastuzumab,
resulting in further reduction in the
growth and survival of HER-2–positive
breast cancer cells.
The labeling for Perjeta includes a
boxed warning regarding the potential
risk for severe fetal injury or fetal death.
Source: FDA, June 8, 2012
Vaccine Protects Children
Against Two Diseases
The FDA has approved Menhibrix
(GlaxoSmithKline), a combination vaccine for infants and children 6 weeks
through 18 months of age, for the prevention of invasive disease caused by
Neisseria meningitidis serogroups C and
Y and Haemophilus influenzae type b.
Diseases caused by N. meningitidis
(meningococcal disease) and H. influenzae type b (Hib disease) can be life-
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threatening. These bacteria can infect
the bloodstream (causing sepsis) and the
lining that surrounds the brain and spinal
cord (causing meningitis). In young children, N. meningitidis and H. influenzae
type b are important causes of bacterial
meningitis.
These two diseases often progress
rapidly and can cause death or serious
consequences such as blindness, mental
retardation, or amputation.
The vaccine’s effectiveness was based
on immune responses in several hundred
infants and toddlers in the U.S. For the
Hib component of the vaccine, immune
responses in infants and toddlers following vaccination with Menhibrix were
comparable to immune responses in infants and toddlers who received an FDAapproved vaccine against invasive Hib
disease. For the meningococcal component, the vaccine produced antibodies in
the blood at levels considered protective
against invasive meningococcal disease
caused by serogroups C and Y.
Menhibrix is given as a four-dose series in children 2, 4, 6, and 12 through
15 months of age. The first dose may be
given as early as 6 weeks of age, and the
fourth dose may be given as late as 18
months of age.
Source: FDA, June 14, 2012
NEW INDICATION
Horizant, an Oral Drug
For Postherpetic Nerve Pain
Originally indicated for patients with
primary restless legs syndrome in 2011,
extended-release gabapentin enacarbil
(Horizant, GlaxoSmithKline/XenoPort)
is now approved to treat postherpetic neuralgia, a complication of shingles. The
drug is administered in one 600-mg dose
for the first 3 days of treatment, followed
by 600-mg doses twice daily on day 4 and
afterward. Dose adjustments are required
for patients with renal impairment. The
dose should be tapered to 600 mg once
daily for 1 week before the end of treat-
ment to reduce the risk of withdrawal
seizures. Adverse events included somnolence, dizziness, headache, nausea,
and fatigue.
Patients taking antiepileptic drugs,
including other gabapentin formulations,
may have an increased risk of suicidal
ideation and behavior, as well as serious
multiorgan hypersensitivity (e.g., fever,
rash, and lymphadenopathy).
Sources: GlaxoSmithKline and www.
medicalnewstoday, June 7, 2012
DRUG NEWS
Counterfeit Adderall
The FDA has announced that counterfeit versions of Adderall tablets (Teva) are
being sold on the Internet. Developed
by Shire, Adderall is an amphetamine
medication approved to treat attentiondeficit/hyperactivity disorder (ADHD)
and narcolepsy. The drug is classified as
a controlled substance.
Although the FDA has not received any
reports of harm, the fake tablets lack the
active ingredient and cannot provide the
appropriate treatment. Teva was alerted
to the problem by a patient who noticed
misspellings on the packaging. Teva’s
Adderall is packaged in bottles, but the
fakes came in foil wrappers.
Adderall is composed of a mixture of
four amphetamines. The fake tablets
contain tramadol (i.e., Ultram, Janssen),
a narcotic-like pain reliever, and acetaminophen. The counterfeit tablets are round
and white with no markings. The authentic tablets are round, orange–peach in
color, and scored with “dp” on one side
and “30” on the other side.
The fake Adderall is sold in a blister
pack, whereas the unadulterated product
is sold in a 100-count bottle. The National
Drug Code (NDC) number is shown as
“NDS,” and Amphetamine Aspartate is
misspelled as Amphetamine Aspartrte
on the fake product.
Adderall is in short supply because
Teva is having difficulty obtaining all of
the active ingredients used in the drug.
Other makers of generic Adderall are also
having trouble meeting demand. The
shortages affect both extended-release
and immediate-release formulations.
The FDA warned consumers to be cautious when buying drugs online, because
rogue Web sites and distributors may
target medications that are in short supply for counterfeiting.
Sources: The Philadelphia Inquirer and
Web MD, May 30, 2012
Introvale Oral
Contraceptives Recalled
Sandoz, a subsidiary of Novartis, has
voluntarily recalled 10 lots of its generic
Introvale oral contraceptive because of
misplaced placebo tablets in the packs. In
the faulty packs, the placebo tablets were
placed in the slot for the 9th week instead
of the correct 13th-week slot.
Affected lot numbers distributed in the
U.S. between January 2011 and May 2012
included LF00478C, LF00479C, LF00551C,
LF00552C, LF00687C, LF00688C,
LF00763C, LF00764C, LF00765C, and
LF01261C.
Women should immediately stop using
the tablets and should switch to a nonhormonal form of birth control. Sandoz
had not received reports of any adverse
reactions, but the recall was initiated as
a precaution.
This marks the fourth major recall of
oral contraceptives this year. In February,
Pfizer, Qualitest, and Glenmark Generics recalled its birth control products
because of packaging errors.
Source: FDA, June 5, 2012
New Rules
For Opioid Prescribing
In an effort to reduce the misuse of
opioid analgesics, Blue Cross Blue Shield
of Massachusetts plans to review physicians before they can prescribe the drugs
for more than 30 days. Physicians will
be allowed to order one 15-day prescrip-
tion and a 15-day refill before they are
reviewed by the insurer.
The goal of the policy, which was
scheduled to begin July 1, is to prevent
access by teenagers and others for whom
the drugs were not prescribed and to prevent physicians from prescribing 60 days
of an analgesic for a minor ailment, such
as a sprained ankle.
Patients with serious or chronic conditions, or those who are terminally ill,
will be allowed to continue to fill their
prescriptions. Physicians must show that
they have developed a treatment plan,
have counseled patients about the drug’s
risks and benefits, have obtained a written agreement, and have identified a prescriber and a pharmacy to reduce doctorshopping before prescriptions beyond 30
days will be authorized by the insurer.
Some physicians and patient advocates
say that the policy could make access to
medications more difficult for patients
with chronic pain, and some primary
care physicians claim that the approval
process will reduce the already limited
amount of time they have with patients.
Opioids are reviewed in this month’s
Continuing Education article on page 412.
Sources: The Philadelphia Inquirer
June 18, 2012; Kaiser Health News/Washington Post, June 11, 2012; The Advisory
Board Company, June 13, 2012, www.
advisory.com
Mixed Messages on Calcium/
Vitamin Supplements
Calcium and Vitamin D Might Not
Prevent Fractures in Some Women …
The U.S. Preventive Services Task
Force recommends that healthy postmenopausal women not take low doses
of calcium or vitamin D supplements to
prevent fractures. This is the same panel that recently recommended against
routine prostate-specific antigen (PSA)
testing for men. The supplement recommendation did not apply to patients with
osteoporosis.
Most people, the panel claimed, are
not calcium-deficient and can probably
achieve sufficient levels with a healthful
diet. For healthy premenopausal women
and men, the panel said there was not
enough evidence to recommend taking
vitamin D, with or without calcium, to
prevent fractures.
The panel analyzed the effects of the
supplements in 137 studies. The doses, at
least for postmenopausal women, consisted of 400 IU units/day or less of vitamin
D and 1,000 mg/day or less of calcium. At
these low doses, calcium and vitamin D
were not considered sufficient to prevent
fractures. There was also a small risk of
kidney stones.
Sources: The New York Times, May 24
and June 12, 2012; The Detroit Free Press,
June 13, 2012
… And They Might Increase
Heart Attack Risk
Patients who take calcium supplements
to increase bone health might be increasing their risk of heart disease. In a study
from New Zealand, calcium supplements
generally raised the risk of cardiovascular
events.
Researchers reanalyzed data from
the Women’s Health Initiative (WHI)
that looked at calcium and vitamin D
supplements. The initial study of 36,000
women showed no increased risk for
heart disease with 1,000 mg of calcium
and 400 IU of vitamin D per day compared
with placebo. However, some women
were also taking calcium supplements
on their own, which could have masked
the initial findings.
The team looked at a subgroup of
16,718 women who were not taking calcium supplements on their own when
the WHI began. In this analysis, women
who were taking calcium and vitamin D
as part of the trial were at greater risk for
heart disease, primarily heart attacks.
An analysis of data from 13 other trials
showed that taking calcium, with or with-
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out vitamin D, could increase the risk of
heart attack and stroke. In another arm of
the WHI, no evidence of increased heart
risk was seen among women who were
randomly assigned to take calcium plus
vitamin D.
The investigators suggested that high
serum calcium levels lead to clotting abnormalities. If a woman’s risk of heart
disease is higher than her risk of osteoporosis and fractures, calcium supplementation might not be recommended.
In another study, Swiss and German
researchers warned that calcium supplements be taken with caution because of a
moderate risk of MI. Over a period of 11
years, men and women who took calcium
supplements had an 86% increased risk
of heart attack compared with those who
used no supplements. However, the actual
number of heart attacks during the followup period was small, with 354 recorded.
There was an association between the
supplements and heart attacks, but the
study did not show cause and effect.
During the follow-up phase, the researchers recorded 260 strokes and 267
deaths from heart disease but found no
link between total dietary calcium and
stroke and no link between total dietary
calcium and deaths from heart disease. A
higher intake of dietary calcium appeared
to reduce the risk of heart attack.
One group of participants who had the
next-to-highest intake of dietary calcium
showed a 31% reduced risk of heart attacks compared with those who ate the
least amount of calcium-containing foods.
However, subjects who took calcium supplements had an 86% higher risk of heart
attacks compared with those who never
took them.
Findings on calcium and heart health
have been inconsistent. Earlier studies
suggested that dietary calcium could
lower the risk of hypertension, obesity,
and type-2 diabetes. Calcium supplements taken once or twice a day appear
to produce different metabolic effects
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compared with calcium in food. A reassessment of the role of calcium supplements for osteoporosis as well as other
conditions is warranted.
Sources: BMJ and WebMD, April 19,
2011; Heart, May 23, 2012, online; Medline Plus, May 24, 2012
… But They Might Reduce Death Rates
In the Elderly
When given with calcium, vitamin D
supplements appeared to be associated
with lower mortality rates in older
individuals, although the data did not
support an effect of vitamin D alone.
Patients receiving both calcium and
vitamin D had a 9% lower mortality rate
during 3 years of treatment than those
not receiving vitamin D, according to
researchers from Denmark.
A previous meta-analysis had shown a
7% relative reduction in the mortality risk
with vitamin D supplements, although
three more recent meta-analyses failed to
support the finding. Two of these, however, showed a significant reduction in
mortality with the combination of calcium
and vitamin D.
The investigstors used data from randomized controlled trials that evaluated
the impact of vitamin D supplementation
on fracture risk. Supplements included
either cholecalciferol (vitamin D3) or
ergocalciferol (vitamin D2).
In those trials, 5.4% of the participants
died during the 3 years of treatment (5.3%
of those receiving vitamin D with or without calcium and 5% of the controls). After
adjustments for potential confounders
were made, including incident hip and
spine fractures, vitamin D supplementation, with or without calcium, was associated with a 7% lower mortality risk. The
reduction was significant for those taking
calcium and vitamin D together, but not
for those taking vitamin D alone.
Calcium, and not vitamin D, might have
a beneficial effect on mortality—which
might be considered counterintuitive, in
light of recently identified risks of MI
associated with calcium supplementation.
The researchers noted that the relative
increase in MI would probably have a
small effect on overall mortality, however.
They speculated that calcium might have
other benefits that outweigh the potential
MI risks (e.g., possibly reducing the risks
of cancer).
The authors suggested that the effects
of calcium and vitamin D, when combined, might be greater than the efffects
of either supplement alone, However, the
finding of lower mortality with calcium
and vitamin D combined, but not vitamin
D alone, could be related to inadequate
doses and methods of administration in
some trials or in differences between the
trials in detecting outcomes.
The analysis was limited by the lack of
data on causes of death, by flaws found
in the original studies, and by the lack
of consistent information on adherence,
self-administered calcium or vitamin D
supplements, and baseline dietary calcium and vitamin D intake.
Earlier in June, the U.S. Preventive Services Task Force had recommended that
for postmenopausal women, there was
no value in supplements up to 400 IU of
vitamin D and 1,000 mg of calcium for
fracture prevention (see page 381).
Sources: J Clin Endocrinol Metab online; MedPage Today, June 15, 2012
Diuretics Improve Cognitive
Function in the Elderly
Potassium-sparing diuretics improved
verbal learning and memory in elderly
individuals who did not have dementia,
according to a post hoc analysis of the
Ginkgo Evaluation of Memory (GEM)
Study. Although the associations were
modest, they were significant and selective, say the researchers.
Many trials have investigated the effects of antihypertensive medications on
cognitive function, with mixed results.
In some trials, angiotensin-converting
enzyme (ACE) inhibitors and diuretics
had protective effects, whereas other
trials showed no effects of ACE inhibitors, thiazide diuretics, or angiotensin
II receptor blockers (ARBs). However,
these earlier studies did not specify the
types of antihypertensive drugs used, and
cognitive function was often a secondary
endpoint.
The current study is an extension of
earlier work, in which the use of diuretics
and ACE inhibitors for more than 3 years
was associated with a reduced incidence
of impairment in memory and executive
function.
A total of 2,707 community-dwelling
individuals 75 years of age and older
without dementia were included in the
analysis; 53% of the participants reported
using antihypertensive medications. Of
these patients, 17% were using a diuretic;
11% were using an ACE inhibitor; 2% were
using an ARB; and 21% were using other
antihypertensive agents.
Compared with participants who did
not use antihypertensive drugs, those using diuretics showed better verbal learning and memory, suggesting a neuroprotective effect. No association was found
between loop and thiazide diuretics and
cognitive function, but potassium-sparing
diuretics were superior to non–potassium-sparing diuretics in enhancing verbal
learning and memory. The researchers
observed no differences in cognitive outcomes between participants receiving
either ACE inhibitors or ARBs compared
with the non-drug group or with users of
other antihypertensive agents.
Source: Alzheimer Dementia 2012;8:
188–195
Nabiximols Spray and Cancer Pain
When a cancer patient’s pain doesn’t
respond to opioids, the simplest answer
may be to use an adjuvant analgesic to
boost the effect of the opioids. However,
researchers in New York, California, Salt
Lake City, Romania, and Mexico suggest
that the paucity of studies in cancer pain,
particularly with respect to adjuvant analgesics, can complicate therapeutic decision making in this regard. The availability of a safe and effective agent for
cancer pain, they say, would be a treatment advance.
Nabiximols (the U.S. name for Sativex,
manufactured in the U.K.) is a cannabinoid that is being investigated as add-on
therapy for cancer pain. In previous studies, nabiximols, an oral spray, relieved
peripheral neuropathic pain, pain and
spasticity from multiple sclerosis, and
cancer pain.
In this study, each activation of the
pump delivered 100 μL of fluid to the
oral mucosa. A total of 360 patients were
randomly assigned to receive nabiximols
or placebo at one of three doses: a low
dose (one to four sprays per day), a
medium dose (six to 10 sprays per day),
or a high dose (11 to 16 sprays per day).
The study design consisted of a 5- to
14-day baseline period, a 5-week titration
and treatment period, and a post-study
office visit after 2 weeks. The maximum
duration of treatment was 9 weeks.
The patients continued their scheduled
opioid dose without changes and used
their breakthrough opioid analgesic as
needed. On each day, they rated their
pain, sleep, use of other drugs, and quality of life, including constipation, daily
functioning, and well-being.
The study’s primary endpoint (a 30%
response) was not significant for nabiximols when compared with placebo. In a
secondary analysis of average daily pain
from baseline to the end of the study,
nabiximols had a greater treatment effect than placebo; however, this effect
was significant only for patients receiving
the low or medium dose of nabiximols.
When those two groups were combined,
the estimated median difference between
treatment groups was 10.5% in favor of
nabiximols.
The low dose of nabiximols provided a
26% improvement in pain compared with
baseline status. Sleep disturbance scores
also decreased slightly with treatment.
However, nabiximols did not have a
positive effect on pain-related functional
impairment, constipation, impression of
global change scores, or overall quality
of life. This lack of clinical improvement
might have been related to the severity
of the disease, the short duration of the
study, or a lack of sensitivity of one or
more questionnaires. Most patients had
advanced disease and multiple comorbidities, and it is likely that the pain relief
achieved with nabiximols could not address the various factors causing functional impairment.
Adverse events were dose-related.
Of the 90 patients receiving high-dose
nabiximols, only 59 (65%) continued
at that dose until the end of the study.
More high-dose patients (28%) withdrew
from treatment, compared with 14% of
the low-dose group, 17% of the mediumdose group, and 18% of the placebo group.
However, serious adverse events were
more common among the low-dose
patients—an unanticipated finding—
compared with the placebo-treated
patients (30% vs. 24%, respectively).
More patients in the low-dose group
died (21%) than in the placebo group
(18%). The deaths appeared to be related
to disease progression.
Source: J Pain 2012;5:438–449
Getting Young Smokers to Quit
Approximately 22% of young adults are
smokers. The years between ages 18 and
24 are critical; that is when the habit becomes entrenched. In some recent studies, however, an increasing number of
young people appear to be willing to try
to quit.
The Department of Health and Human
Services has clinical practice guidelines
for smoking cessation in adults, but they
do not specifically address young adults,
say researchers at the University of Iowa,
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the University of Illinois at Chicago, and
the University of Michigan. Young adults
are more likely to smoke fewer cigarettes
than older adults and are less likely to
smoke daily. That means that nicotine
dependence might be less of a factor for
them.
The researchers gathered data
from 14 studies to determine which
smoking-cessation programs might
work best for younger smokers. Looking
at pharmacotherapy with nicotine
replacement or bupropion (Wellbutrin,
GlaxoSmithKline) and at cognitive–
behavioral therapy, counseling, and social
support, the researchers discovered that
it wasn’t the tools that mattered; it was
the motivation to use the tools. Further, it
wasn’t necessarily the type of intervention
that made the difference; it was the fact
that the smoker used the intervention.
All interventions in young adults were
associated with a higher chance of
quitting smoking as they were for older
people. Motivating younger smokers to
make use of evidence-based treatments
seems to be the key to success.
Source: Am J Prev Med 2012;42:655–
662
Body Weight Affects
Vasopressin Therapy
The standard method of administering
vasopressin by a fixed dose might put
some patients at risk, say researchers at
Sinai–Grace Hospital in Detroit and at the
University of Michigan. A retrospective
study of 64 patients with septic shock
showed that a patient’s weight might
influence how the drug works.
The study was designed to determine
the short-term effects of vasopressin on
catecholamine dosing requirements and
to see whether those effects were related
to body weight. Secondary objectives included evaluations of blood pressure and
heart rate. The primary outcome was the
relationship between the change in catecholamine vasopressor dosing require-
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ments at 0, 2, and 4 hours compared with
the hour before the start of vasopressin
(baseline minus 1 hour) and vasopressin
dosing adjusted for body weight.
Sixty patients were receiving norepinephrine monotherapy at the time of
vasopressin initiation, and three patients
were receiving norepinephrine with dopamine, epinephrine, or phenylephrine. One
patient was being treated with dopamine
monotherapy.
Most patients received vasopressin at
a dose of 0.04 U/minute. Three patients
received doses of 0.02, 0.03, and 0.033 U/
minute. The weight-adjusted dosing of
vasopressin ranged from 0.229 to 0.871
μU/kg per minute—nearly a four-fold
difference.
Changes in vasopressor administration were significantly correlated with
weight-adjusted vasopressin at 2 hours
and 4 hours. Vasopressin was associated
with significant increases in systolic and
diastolic blood pressure and mean arterial pressure at each time point, compared
with values at baseline. Heart rate was
significantly reduced at 2 hours and 4
hours compared with the previous time
point. Thus, a patient’s body weight might
be an important consideration when determining the effects of vasopressin on
catecholamine dosing requirements.
Source: J Crit Care 2012;27:289–293
More Evidence That
Daily Aspirin May Increase
Risk of Bleeding
Taking daily low-dose aspirin to prevent heart disease may increase the risk
of gastrointestinal (GI) or cerebral bleeding, Italian researchers found. In a large
study, daily aspirin was associated with a
55% relative increase in the risk of major
bleeding (an excess of two cases of bleeding per 1,000 patients treated each year).
Diabetic patients had a high rate of major bleeding whether or not they were
using aspirin. It was thought that diabetes
might represent a different population in
terms of the benefits and risks associated
with antiplatelet therapy.
Aspirin has long proved effective for
secondary prevention in patients with
a moderate-to-high risk of cardiovascular events, but the drug’s benefit in the
primary prevention of heart disease has
been controversial. Diabetes may impose
an increased risk of hemorrhage.
The researchers evaluated data from
patients who had received new prescriptions for low-dose aspirin (300 mg or
less). Over a median follow-up period of
5.7 years, the overall rate of hemorrhagic
events was 5.58 per 1,000 person-years
for aspirin users, compared with 3.60 per
1,000 person-years for non-aspirin users.
In addition, an excess risk of both GI and
intracranial bleeding was associated with
aspirin use.
Aspirin use and the risk of bleeding
increased with age. Bleeding rates were
higher in men and in patients taking
antihypertensive agents, prescription
nonsteroidal anti-inflammatory drugs
(NSAIDs), and other antiplatelet and
antithrombotic agents. However, diabetes
was independently associated with an
increased risk of major bleeding. Aspirin
use resulted in only a slightly increased
risk of bleeding in diabetic patients,
suggesting that aspirin’s efficacy in
suppressing platelet function is reduced in
that group. This finding might be related
to the accelerated platelet turnover seen
in diabetes, the researchers said.
Statins were associated with reduced
GI and intracranial bleeding, which could
be attributable to the concomitant use
of proton pump inhibitors (PPIs) in this
population. Obesity, smoking, alcohol
consumption, and the use of over-thecounter NSAIDS or over-the-counter
aspirin were not considered.
The results suggest that aspirin can be
used in patients at intermediate or high
risks of bleeding, but it is important to
know a patient’s risk factors before prescribing aspirin.
Sources: JAMA 2012;307(21):2286–
2294; 2318–2320; MedPage Today, June
5, 2012
Sources: Medical Progress Today.com,
May 24, 2012; Wall Street Journal online,
June 4, 2012
RESEARCH NEWS
Hormone Therapy Can Provide
Benefits for Younger Women
New Herceptin Conjugate
For Breast Cancer
New analyses of hormone therapy
(HT) for menopausal symptoms, published by the International Menopause
Society, suggest that HT is not as risky
as had been thought, especially if it is
started in younger women approaching
menopause. The benefits of HT may also
outweigh the risks for women with severe
symptoms.
For a decade, the large governmentsponsored Women’s Health Initiative
(WHI), terminated in July 2002, had left
the impression that HT was dangerous for
all menopausal women, regardless of age
or symptom severity. Actually, the WHI
study primarily involved older women
(most were 60 years of age or older), and
the average study participant was postmenopausal for an average of 12 years.
The WHI found that HT was associated
with higher rates of heart disease, stroke,
and breast cancer, compared with placebo, in that age group. Over the years,
however, these findings were generalized
to all women.
Subsequent studies reported that
younger women (50–59 years of age)
who started HT near menopause had
fewer cardiovascular problems and fewer
deaths from any cause than women who
started treatment years later. Women who
took only estrogen also had lower risks of
heart disease and breast cancer.
More recent analyses indicate that
women who start using HT before the
age of 60 or within 10 years of menopause
are more likely to derive clinical benefits
compared with those who use HT later in
life. Nevertheless, both the U.S. Preventive Task Force and the North American
Menopause Society recommend against
using HT to prevent chronic diseases.
An experimental drug being developed
by Roche delayed disease progression
and appeared to improve survival in women with a specific type of breast cancer.
T-DM1 combines Roche’s trastuzumab
(Herceptin) with a potent chemotherapy
agent and is delivered directly to cancer
cells. The two drugs in combination are
considered to be more effective in treating tumors than trastuzumab alone; the
combination also causes fewer adverse
events associated with chemotherapy.
Trastuzumab targets the HER-2 protein, which is found on 20% to 25% of
breast cancer tumors. The other components of T-DM1 are emtansine, which
is too potent to be delivered as a conventional medication, and a linker that
connects the two drugs. Both emtansine
and the linker were developed by ImmunoGen Inc.
T-DM1 is an antibody–drug conjugate.
Genentech, a Roche subsidiary, has 25
such agents under development for different cancers, including eight in human
studies. The first agent of this type to gain
FDA approval was Adcetris (Seattle Genetics), which is indicated for Hodgkin’s
lymphoma and another rare cancer.
The recent EMILIA study enrolled approximately 1,000 women with HER-2–
positive breast cancer who had previously
received trastuzumab and a traditional
chemotherapy drug. About half of the
women were then treated with T-DM1,
and the other half were treated with gemcitabine (Xeloda, Roche) plus lapatinib
(Tykerb, GlaxoSmithKline).
Median progression-free sur vival
for patients receiving T-DM1 was 9.6
months, compared with 6.4 months for
those receiving gemcitabine/lapatinib
(a statistically significant difference).
At 2 years, 65.4% of the T-DM1 group
was alive, compared with 47.5% of the
comparator group.
More patients who were treated with
T-DM1 had elevated liver enzyme levels
and thrombocytopenia, whereas more
patients treated with gemcitabine/
lapatinib required dose reductions;
these patients also experienced diarrhea,
vomiting, and swelling and pain of the
hands or feet.
Roche plans to file for FDA approval of
T-DM1 by the end of 2012.
Source: The Wall Street Journal, June
4, 2012
Breast Cancer Recurrence
Linked to Circulating
Tumor Cells
In a prospective study conducted at the
MD Anderson Cancer Center in Houston,
finding even one circulating tumor cell at
the time of surgery correlated with more
than a four-fold risk of death or recurrence over a follow-up period of 2 years in
patients with nonmetastatic breast cancer.
The risk of cancer recurrence increased
with the number of tumor cells detected
in peripheral blood.
Circulating tumor cells had proved to
be prognostic in previous studies. The
new results suggest that a blood test
might be a minimally invasive way of
obtaining more information. However,
although the test is commercially available, it is not ready for routine clinical use
in early-stage breast cancer.
The study included 302 patients with
operable stage 1 to 3 breast cancer who
did not have bilateral disease or any
other malignancy within 5 years of the
diagnosis.
Overall survival was 4.04-fold less likely at 2 years for patients with at least one
tumor cell detected in a baseline blood
sample. The patient’s nodal status did
not predict the presence of circulating
tumor cells.
One promising use of the blood test
Vol. 37 No. 7 • July 2012 • P&T 385
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might be to compare levels of circulating
tumor cells at baseline and after one or
two cycles of chemotherapy to determine
whether it is necessary to change agents.
It is too early to tell whether current
treatment could eradicate circulating tumor cells or even whether such treatment
is necessary for better outcomes.
Sources: Lancet Oncol June 2012;
MedPage Today, June 5, 2012
Blood Test of Immune System
Activity May Predict Early Death
A blood test that measures a marker of
immune system activity may help doctors
identify people who are at risk of dying
at an early age. Mayo Clinic researchers
measured levels of immune system molecules known as free light chains in
almost 16,000 residents of Minnesota
50 years of age and older. Those with
molecule levels in the top 10% were four
times more likely than the other study
participants to die over the next 13 years.
Doctors commonly test for free light
chains to diagnose and manage blood
disorders and blood-related cancers. This
study is the first to link high levels of free
light chains with early death in people
without any known blood disorders.
Generally, light chains bind with
heavy chains to form infection-fighting
antibodies. The presence of unattached
“free” light chains has long been recognized as a signal that the immune
system has gone awr y because of
inflammation, infection, or both.
The investigators recommended
that the test not be used as a screening
instrument, because the results might
alarm patients and the test might not be
any more powerful than existing methods
of measuring immune system function or
inflammatory markers, such as C-reactive
protein.
The authors did not compare the free
light chain test with these other tests.
Sources: Mayo Clin Proc June 2012;
Science Daily, June 4, 2012
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Cymbalta Reduces Pain
After Chemotherapy
In preliminary findings presented at
the American Society of Clinical Oncology (ASCO) annual meeting, held in June,
the antidepressant drug duloxetine (Cymbalta, Eli Lilly) appeared to reduce the
numbness and tingling associated with
taxane- or platinum-based chemotherapy.
Pain from chemotherapy-induced
peripheral neuropathy and its interference with daily life showed a significant
decrease after treatment with the drug.
A significant reduction in pain scores
occurred in 33% of duloxetine patients
compared with 17% of placebo patients.
Duloxetine, a serotonin–norepinephrine
reuptake inhibitor (SNRI), is thought to
increase the amount of pain-inhibiting
neurochemicals in the brain, such as
dopamine.
The study included 220 patients (mostly
survivors of breast and gastrointestinal
cancer) with peripheral neuropathy that
had been induced by paclitaxel (Taxol,
Bristol-Myers Squibb) or oxaliplatin (Eloxatin, Sanofi). Patients received doubleblind treatment with either duloxetine or
placebo.
More duloxetine-treated patients experienced at least some pain reduction
compared with placebo-treated patients
(59% vs. 38%, respectively). Duloxetine
was well tolerated and caused fewer adverse events than were seen in previous
trials of patients with diabetic neuropathy.
Sources: ASCO meeting 2012; MedPage
Today, June 4, 2012
Cochrane Reviews
Tight Glucose Control Prevents
Neuropathy, but What Is the Risk?
Aggressive control of blood glucose
levels in diabetes can help prevent painful neuropathy, according to a review in
The Cochrane Library. However, optimal
target levels need to be established to
prevent complications.
Up to 50% of patients with diabetes
develop diabetic neuropathy, a disabling
condition that affects ner ves in the
feet and legs. It is possible to prevent
neuropathy with insulin regimens and
diet modifications, but the effects of this
approach have not been systematically
reviewed until now.
Researchers reviewed the results of
six studies that investigated the risk
of neuropathy in people who received
enhanced glucose-control treatments,
including extra insulin injections,
antidiabetic drugs, and dietary changes.
The review considered evidence in
type-1 and type-2 diabetes separately.
In two studies involving 1,228 patients
with type-1 diabetes, significantly fewer
patients developed neuropathy each year
with enhanced glucose-control treatment
compared with those receiving routine
care. In four studies involving a total of
6,669 patients with type-2 diabetes, there
was only a small, insignificant reduction
in new cases of neuropathy.
A more aggressive approach to
controlling glucose levels seems to
delay the onset of neuropathy. The less
dramatic effects in patients with type2 diabetes suggest that other factors,
besides high glucose levels, play a role
in causing ner ve damage. However,
the risk of adverse effects, including
hypoglycemia, was higher with enhanced
glucose control. Future studies should
establish target levels for glucose control
that will balance the benefits and side
effects of this approach, the researchers
said.
Source: Cochrane Database of Syst Rev,
June 13, 2012, Issue 6, Art. No. CD007543
Weekly Fertility Treatment Works
As Well As Daily Treatment
New long-lasting weekly injections of
fertility hormones appear to be as safe
and as effective as standard daily injections.
Women undergoing fertility treatments are usually given daily injections
continued on page 391
July 2012 • Vol. 37 No. 7
continued from page 386
of follicle-stimulating hormone (FSH) to
increase the number of eggs that their
ovaries release each month. In in vitro
fertilization and intracytoplasmic sperm
injection, the eggs are then removed
and fertilized outside the body. Daily
hormone injections can be painful and
stressful.
A longer-lasting form of FSH (corifollitropin alfa) was recently introduced.
One injection can replace the first 7 days
of FSH injections that are required with
the standard regimen. Women who received medium doses of the new hormone
weekly were as likely to become pregnant
and had no more chance of a miscarriage
or an ectopic pregnancy compared with
women who received daily FSH injections.
Further study is needed to establish
whether the weekly regimen is as effective
for women who respond poorly to fertility hormones and for those who produce
higher than expected numbers of eggs.
Source: Cochrane Database Syst Rev,
June 13, 2012, Issue 6, Art. No. CD009577
DEVICE NEWS
Sales of Vaginal Mesh Halted
Ethicon, a subsidiary of Johnson &
Johnson, will stop marketing most of its
vaginal mesh implants. The company will
no longer sell TVT Secur and the Prosima, Prolift, and Prolift + M pelvic floor
repair system products. Lawsuits have
been filed by about 1,000 women who
claim that the products caused internal
injury.
Ethicon asked the FDA to grant it 120
days to notify customers of the change
and to enable hospitals and surgeons
to choose alternative treatments. The
company also requested a label update
for its Gynemesh PS product, restricting
its use in abdominal sacrocolpopexy, a
procedure for treating pelvic organ
prolapse.
Last year, the FDA warned that using
the mesh to treat pelvic organ prolapse
might carry more risks and confer less
benefit than other surgical options. The
mesh was considered to be associated
with vaginal tissue erosion, pain, infection, bleeding, pain during intercourse,
and urinary problems, along with organ
perforation from surgical tools used to
place the mesh. Some reports cited the
need for additional surgeries to treat complications or to remove the mesh.
In September, an FDA advisory panel
called for a more rigorous premarket
approval process for mesh used to treat
pelvic organ prolapse. The move is yet
another setback for Johnson & Johnson,
which has been dealing with recalls of
Tylenol, hip replacements, and other
products for nearly 2 years.
Sources: Reuters and MedPage Today,
June 5, 2012
New Medical Devices
Marvin M. Goldenberg, PhD, RPh, MS
Name: PioNIR plus Stent (Presillion
plus CoCr Coronary Stent on RX System)
Manufacturer: Medinol/Cordis/
Johnson & Johnson, Israel
Approval Date: May 13, 2012
Purpose: This bare-metal stent is
used to open narrowed coronary arteries caused by buildup of plaque in patients
with coronary artery disease. The system
is to be used in coronary arteries 30 mm
or less in length and with reference vessel
diameters of 2.5 mm to 4.0 mm.
Description: A catheter with a small
balloon mounted on the end is inserted
into a blood vessel in the groin or arm
and is advanced into a coronary artery.
The catheter is then placed at the narrowed portion of the artery, and the balloon is inflated. As the balloon inflates, it
stretches the coronary artery wall. The
balloon is then deflated, and the catheter
is removed from the artery. The stentdelivery catheter is then positioned at
the narrowing of the coronary artery.
The balloon on the stent-delivery catheter
is inflated, which expands the stent and
presses it against the coronary artery
wall. The stent remains permanently
implanted within the coronary artery to
maintain patency.
Benefit: The stent improves blood
flow and may relieve angina. This is the
only stent that is capable of differential
cell lengthening. This enables the stent to
conform to the natural curve of the vessel
in the expanded configuration.
Source: www.fda.gov
Name: Mcompass Anorectal
Manometry Device
Manufacturer: Medspira Inc.,
Minneapolis, Minn.
Approval Date: May 21, 2012
Purpose: The device is used to evaluate pelvic floor function in patients with
constipation or fecal incontinence. The
tests are used to measure the pressures
of the anal sphincter muscles, sensation
in the rectum, and the neural reflexes needed for normal bowel movements.
Description: The device is portable
and weighs only 3 pounds. With comparative systems, a cart and a dedicated room
are required, whereas the Mcompass can
be set up anywhere in minutes. Testing
can be easily conducted in nursing homes
or other community facilities.
Built-in software prompts guide new
users through the testing process. Results are displayed in real time on the tablet personal computer workstation. The
encrypted data packet can be e-mailed to
others for interpretation, if needed, via
built-in wireless connectivity.
A disposable catheter for enhanced
testing accuracy and a single connector
to streamline the setup are included.
The catheter consists of a central
rectal balloon and four radial anal-canal
balloons at 90-degree relative positioning.
Each balloon provides independent
measurements. The anal canal balloon
is 20 mm long, enabling one or two positioned measurements.
Benefit: The technology is designed
for use by colorectal surgeons, primary
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continued from page 391
care physicians, gastroenterologists,
gerontologists, urogynecologists, and
obstetrician–gynecologists.
Sources: www.businesswire.com;
www.healthflashmarketing.com; www.
medspira.com/mcompass
Name: Epic Vascular Self-Expanding
Stent
Manufacturer: Boston Scientific
Corp., Natick, Mass.
Approval Date: May 22, 2012
Purpose: The Epic stent is used to
open blocked arteries in patients with
iliac artery stenosis, a form of peripheral
vascular disease.
Description: The self-expanding
nitinol stent is designed to sustain
vessel patency while providing enhanced
visibility and accuracy during placement.
Stent flexibility and fracture resistance
are featured. All stent sizes are compatible
with 6 French sheaths. The stent-delivery
system is available in shaft lengths of
75 cm and 120 cm for all sizes and is
compatible with 0.035-inch guide wires.
Benefit: In an intent-to-treat population, only 3.4% of patients experienced
a major adverse event during a 9-month
period. This rate was significantly lower
than the prespecified performance goal
of 17%.
Sources: www.masshightech.com;
www.bostonscientific.com
Device Recall
Curlin Infusion Administration Sets,
made by the MOOG Medical Devices
Group, were recalled on May 18, 2012,
because of the potential for the reverse
pump segment in the set. The sets deliver
drugs and other fluids. The malfunction
may cause fluids or medications to flow
in reverse from what was intended,
resulting in delayed or deficient therapy.
Use of the affected sets may also cause
serious adverse health consequences,
including death.
Source: FDA, June 1, 2012 n
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