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P T. 2012;37(7): 380-386, 391, 422

New Drugs/Drug News/New Medical Devices July 2012


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-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 FDA-approved 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


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 treatment 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


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 attention-deficit/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 non-hormonal 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 prescription 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 doctor-shopping 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,

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 post-menopausal 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 without 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 follow-up 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 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 neuropro-tective 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 medium-dose 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, 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 requirements 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-the-counter 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


Hormone Therapy Can Provide Benefits for Younger Women

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 government-sponsored 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 post-menopausal 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.

Sources: Medical Progress, May 24, 2012; Wall Street Journal online, June 4, 2012

New Herceptin Conjugate For Breast Cancer

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 survival 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 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 awry 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

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 double-blind 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 nerves 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 type-2 diabetes suggest that other factors, besides high glucose levels, play a role in causing nerve 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 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


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


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 stent-delivery 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.


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 care physicians, gastroenterologists, gerontologists, urogynecologists, and obstetrician–gynecologists.


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%.


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