SAN FRANCISCO, April 27 — Lapatinib (Tykerb) may offer an option for inflammatory breast cancer when other treatments have failed, researchers said.

• Explain to interested patients that inflammatory breast cancer is a relatively uncommon but aggressive tumor type with few treatment options once patients have failed chemotherapy and trastuzumab.
• Caution patients that lapatinib monotherapy is not FDA approved for treating refractory or relapsed inflammatory breast cancer.

Lapatinib yielded tumor responses in 39% of women with HER2+ inflammatory breast cancer heavily pretreated with chemotherapy, including trastuzumab (Herceptin), Bella Kaufman, M.D., of the Chaim Sheba Medical Center in Tel Hashomer, Israel, and colleagues found.

In the phase II study, lapatinib responses lasted 20.9 weeks on average, a clinically meaningful effect, the researchers reported online in The Lancet Oncology.

Inflammatory breast cancer is an aggressive type with a higher frequency of HER2 overexpression than other breast cancers (40%).

Treatment is typically multimodal involving neoadjuvant combination chemotherapy followed by surgery, adjuvant chemotherapy, or radiotherapy.

For patients with tumors overexpressing HER2 who are refractory to or fail these treatments, there are currently no other options, Dr. Kaufman’s group noted.

Since lapatinib is a tyrosine kinase inhibitor selective for HER2, the researchers tested its efficacy in a phase II study of 126 patients with relapsed or refractory HER2+ inflammatory breast cancer.

Prior treatment included more than four chemotherapy regimens for 61% of patients, trastuzumab for 75%, and more than three trastuzumab regimens for 9%.

All patients got lapatinib 1,500 mg once a day in a nonrandomized, open-label fashion.

None of the patients had a complete response, defined as disappearance of all measurable disease on combined clinically evaluable skin-disease criteria and RECIST criteria, although one had response as measured by skin disease only.

After a median 12.1 weeks of lapatinib, 39% of the women (95% confidence interval 30% to 48%) met the primary endpoint of an objective response with at least a 50% decrease in the extent of skin disease from baseline.

Looking only at the clinically evaluable skin-disease criteria, the objective response rate was 40% (95% CI 31% to 50%), but the rate by RECIST criteria that included only patients with measurable sites of locally advanced or metastatic disease at baseline was just 15% (95% CI 9% to 24%).

Response rates were lower in patients previously treated with trastuzumab (35% versus 48%). But among those who responded, median overall survival after the first lapatinib dose was not significantly different for those who had prior trastuzumab treatment (18.4 versus 14.0 months).

In fact, patients with prior trastuzumab exposure who responded to lapatinib had the longest survival of any group, followed by those who responded without prior trastuzumab treatment.

“This finding confirms the clinical benefit of targeted therapy in these patients,” Dr. Kaufman’s group said.

Adverse event rates and severity were similar to that seen in prior lapatinib monotherapy studies.

Although 32% of patients had at least one serious adverse event, most were judged to be not treatment related. The most common of these were dyspnea (6%) and pleural effusion (4%).

Five patients (4%) died from adverse events considered to be possibly treatment related: one case of acute hepatitis and abdominal sepsis; one case of dyspnea, cyanosis, and pyrexia; one of pulmonary edema; one of superior mesenteric artery syndrome; and one case of jaundice.

However, the researchers noted, these fatal serious adverse events were also possibly related to underlying disease. “The cause of these events is difficult to discern because of the poor clinical outcome inherent in this heavily pretreated population of patients with inflammatory breast cancer.”

The study was funded by GlaxoSmithKline . Five of the researchers reported being employees or former employees of GlaxoSmithKline and holding stock in the company. One reported serving as a consultant to GlaxoSmithKline for the development of a skin scale of measurement for another trial, receiving travel grants from the company, and having given expert testimony at FDA and Health Canada presentations. Another reported having received honoraria from GlaxoSmithKline .

Primary source: The Lancet Oncology

Source reference:

Kaufman B, et al “Lapatinib monotherapy in patients with HER2-overexpressing relapsed or refractory inflammatory breast cancer: final results and survival of the expanded HER2+ cohort in EGF103009, a phase II study” Lancet Oncol 2009; DOI:10.1016/S1470-2045(09)70087-7.

CHICAGO, April 27 — A man’s PSA value at age 60 reliably predicted the risk of fatal prostate cancer over the next 25 years, according to data from a Swedish study.

• Explain to patients that this study showed that a man’s PSA value at age 60 predicted the risk of dying of prostate cancer to age 85.
• The findings require validation in other patient populations.
• Note that this study was published as an abstract and presented orally at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

Men who had PSA values below the median of ?1 ng/mL had less than a 1% risk of dying of prostate cancer by age 85, Hans Lilja, M.D., of Memorial Sloan-Kettering Cancer Center in New York, reported at the American Urological Association meeting.

At the other end, the risk of fatal prostate cancer soared into double digits in men who had a PSA value of 3 to 4 ng/mL or higher at age 60.

“Sixty-year-old men with PSA at or below the population median can be advised that although they may harbor cancer, it is unlikely to become life threatening,” said Dr. Lilja. “Those with PSA elevated above thresholds such as 3 or 4 ng/mL are at greatly increased risk of clinically diagnosed prostate cancer and prostate cancer-specific death.”

Men with PSA values below those that trigger prostate biopsies have a substantial risk of developing prostate cancer. However, the clinical focus should be on men who have an increased risk of developing symptomatic or fatal prostate cancer, not prostate cancer per se, said Dr. Lilja.

“Screening and chemoprevention in men age 60 and above should focus on subgroups of men with PSA levels strongly associated with symptoms or death,” he asserted.

To investigate the relationship, researchers analyzed data from the Malmo Prevention Project, a study of cardiovascular disease conducted from 1974 to 1986 in Malmo, Sweden. PSA testing was uncommon at that time, but frozen plasma samples from study participants permitted PSA assessment more than two decades later.

The analysis included 1,167 men who were born in 1921 and whose blood samples were obtained during 1981 and 1982. Researchers followed the men until death or age 85, whichever came first.

Dr. Lilja said 133 men (11.4%) developed prostate cancer during follow-up, and 31 men (2.7%) died of prostate cancer.

The median PSA value for the entire study group was 1.06 ng/mL. Men who had PSA values at or below the median at age 60 had a 0.3% risk of prostate cancer death by age 85.

The risk of dying of prostate cancer by age 85 increased to 1.5% in men whose PSA value was 1.5 ng/mL at age 60 (67th percentile). Prostate cancer mortality increased to 3.7% in men who had a PSA level of 2.1 ng/mL at age 60 (80th percentile).

From 2.1 to 3.4 ng/mL (90th percentile), the risk of fatal prostate cancer increased to 8.9%. The risk almost doubled to 15% with a PSA value of 5.2 ng/mL at age 60 (95th percentile) and doubled again to 31% with a PSA value of 15 ng/mL (99th percentile).

Two thirds of prostate cancer deaths involved men who had PSA values ≥3.4 ng/mL. A PSA value of 1.5 ng/mL at age 60 identified 90% of the men who would subsequently die of prostate cancer. The median value for the study population (1.06 ng/mL) comprised 93% of all prostate cancer deaths.

Dr. Lilja said the findings must be reproduced in other populations before they can be applied to clinical practice.

Dr. Lilja and colleagues reported no competing interests.

Primary source: American Urological Association

Source reference:
Vickers AJ, et al “Prostate-specific antigen level at age 60 and death from prostate cancer” AUA 2009; Abstract 162.

CHICAGO, April 28 — Men who were taking statins at the time of radical prostatectomy had a 30% reduction in prostate cancer recurrence, data reported here showed.

Statin users also had lower PSA values and were more likely to have T1 disease than nonusers, Robert J. Hamilton, M.D., of the University of Toronto, said at the American Urological Association meeting.

“Our findings suggest that statins may slow prostate cancer progression after radical prostatectomy,” said Dr. Hamilton. However, he emphasized, “at this point we cannot say with confidence that statins reduce the risk of prostate cancer recurrence after radical prostatectomy.”

He said the findings require confirmation in other studies, such as a randomized controlled trial placing men on statins who are about to undergo surgery.

• Explain to patients that use of statin drugs has been associated with benefits related to several urologic conditions.
• All of the data came from retrospective studies of databases and therefore do not prove that statins are beneficial for the conditions.
• Note that these studies were published as abstracts and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

Dr. Hamilton’s study was one of a half-dozen statin-related abstracts featured at an AUA press briefing. Collectively, the studies suggested that statins have favorable effects on prostate cancer risk, lower urinary tract symptoms (LUTS), benign prostatic hyperplasia (BPH), and erectile dysfunction.

Dr. Hamilton reported findings from a study of 1,325 men who underwent radical prostatectomy for prostate cancer. Information collected before surgery included current statin use — 237 (18%) men were taking one of the drugs at the time of surgery. The principal outcomes were pathologic features of the cancer and biochemical recurrence.

There were no differences between those taking statins and those not taking the drugs with respect to the frequency of positive surgical margins, seminal vesicle invasion, extracapsular extension, or lymph node metastases. However, significantly more statin users had a Gleason score of 7 (60% versus 49%, P=0.003).

Statin users presented a mixed bag of risk characteristics. They had a lower mean PSA value (6.2 ng/mL versus 6.9 ng/mL, P=0.04), and 67% of statin users had stage T1c disease compared with 58% of nonusers (P=0.009).

On the negative side, statin users were 2 years older and had a higher rate of obesity, as well as the higher proportion of Gleason 7 disease.

In a multivariate analysis, statin users had an odds ratio for recurrence of 0.70 compared with nonusers (95% CI 0.50 to 0.97, P=0.03).

Adding to statins’ association with prostate cancer, Lionel Banez, M.D., of Duke University in Durham, N.C., reported findings from an analysis of obesity, statin use, and tumor inflammation.

Mounting evidence suggests inflammation may play a role in prostate cancer evolution and progression. Obesity has been associated with inflammation and more aggressive cancer, Dr. Banez said. Statins, on the other hand, have well-documented anti-inflammatory activity and have been associated with reduced cancer risk.

Dr. Banez and colleagues reviewed data on 254 men who underwent radical prostatectomy. About half of the patients reported statin use.

One pathologist graded all of the surgical specimens with respect to inflammatory infiltrates.

Significantly more statin users were overweight (48%) and obese (31%, P<0.001). However, increasing body mass index had only a marginal association with inflammation (OR 2.16, P=0.07).

In a multivariate analysis, statin use was associated with a 72% reduction in the risk of tumor inflammation (OR 0.28, P=0.01).

Stacy Loeb, M.D., of Johns Hopkins, summarized findings from a study that examined statin use and tumor characteristics associated with aggressive disease. The study involved 1,282 men who underwent radical prostatectomy from 2003 to 2008 and included 418 patients who reported statin use at the time of surgery.

Statin users had a significantly lower tumor volume, percentage of cancer in the prostatectomy specimen, prevalence of positive surgical margins, and Gleason score of 7 to 10.

Collectively, the findings suggested statin use was associated with more favorable tumor features at prostatectomy.

The remaining studies came from the Mayo Clinic in Rochester, Minn. Rodney Breau, M.D., presented findings from an analysis of 2,427 men who participated in an observational study of prostate cancer. The cohort included 618 statin users.

During a median follow-up of 14.1 years, 75 (12.2%) statin users had a prostate biopsy and 30 (4.9%) had a prostate cancer diagnosis. Compared with nonusers, patients who used statins had more than a 60% reduction in the odds ratio for prostate biopsy and prostate cancer diagnosis.

Among patients who had biennial PSA measurements, statin users were 65% less likely to have PSA values that exceeded age-specific thresholds.

Dr. Breau offered two possible interpretations of the results: The effect of statins on PSA values might account for the lower rates of biopsy and prostate cancer diagnosis. Alternatively, statin use may lower the risk of developing prostate cancer.

Jennifer L. St. Sauver, M.D., reviewed data from a study examining the impact of statins and nonsteroidal anti-inflammatory drugs (NSAIDs) on benign urinary conditions, specifically LUTS and BPH. Records for 2,447 men showed 729 were using statins.

Statin users had a 63% reduction in the odds ratio for moderate or severe LUTS (as defined by AUA symptoms score), a 52% reduction in the frequency of reduced urinary flow, and a 57% reduction in the odds ratio for prostatic enlargement. The magnitude of the reductions increased with duration of statin use, said Dr. St. Sauver. Men who reported taking statins and NSAIDs had even greater reductions in the outcomes assessed.

Ajay Nehra, M.D., presented data from an analysis of statin use and erectile dysfunction (ED) in the same 2,447 men, including 2,075 who had complete data on erectile function and use of phosphodiesterase type 5 (PDE-5) inhibitors.

Dr. Nehra and his colleagues excluded men with ED or PDE-5 inhibitor use at baseline, those who had no regular sexual partner, and those who had a history of prostate cancer, leaving 1,480 for the analysis. Of those, 417 were statin users.

The statin users had a significantly higher prevalence of comorbid conditions that could adversely affect sexual function, including diabetes, hypertension, and coronary disease. Additionally, statin users were significantly more likely to be taking NSAIDs, antidepressants, and drugs to treat LUTS or BPH.

After adjustment age, comorbidities, and medication use, men taking statins had a 37% reduction in the hazard ratio for ED (HR 0.63, 95% CI 0.51 to 0.77).

Moreover, the risk of ED was lowest in men who had taken statins for the longest period of time.

Collectively, the presentations reflected the growing body of literature suggesting that statins influence PSA levels and certain aspects of prostate cancer risk, said J. Brantley Thrasher, M.D., of the University of Kansas in Kansas City, who moderated the press briefing.

However, he said, the studies reported to date have not provided enough information to warrant prescribing statins for prostate cancer or other urologic conditions.

Dr. Banez disclosed relationships with AstraZeneca and Veridex. Dr. Nehra disclosed relationships with GlaxoSmithKline , Pfizer, and sanofi-aventis. Dr. Thrasher disclosed a relationship with sanofi-aventis.

,

Primary source: American Urological Association

Source reference:
Hamilton RJ et al “Statin medication use and the risk of biochemical recurrence following radical prostatectomy: results from the SEARCH database” AUA 2009; Abstract 1598.

Additional source: American Urological Association

Source reference:
Banez LL et al. “Association between statins, obesity, and prostate tumor inflammatory infiltrate in men undergoing radical prostatectomy” AUA 2009; Abstract 575.

Additional source: American Urological Association

Source reference:
Loeb S et al. “Is statin use associated with prostate cancer aggressiveness?” AUA 2009; Abstract 576.

TORONTO, April 28 — Acrylamide, the suspected carcinogen found in potato chips and french fries, is not associated with an increased risk of lung cancer, Dutch researchers found.

• Explain to interested patients that animal studies raised fears that acrylamide, a compound that arises in some cooked foods, might be a carcinogen.
• Note that this study suggests there is no link to lung cancer in men and a possibly protective association in women.

In male participants in a large case-control study, there was no link between the disease and consumption of foods high in acrylamide, according to Janneke Hogervorst, M.Sc., of Maastricht University, in the Netherlands, and colleagues.

On the other hand, in women, eating more of the compound appeared to be associated with a lower risk of lung cancer, the researchers reported online in the Journal of the National Cancer Institute.

Acrylamide is found in commonly consumed carbohydrate-rich heated foods, such as french fries and potato chips, and is classified as a probable human carcinogen based on results from animal studies.

The evidence on links to human cancers, on the other hand, is mixed, with some studies showing a link and others finding no association.

To clarify the issue in lung cancer, the researchers turned to the Netherlands Cohort Study on Diet and Cancer, which includes 58,279 men and 62,573 women ages 55 through 69.

They estimated intakes of acrylamide-containing foods and risk factors for

cancer using a self-administered questionnaire at baseline in 1986. Those data were combined with acrylamide levels in relevant Dutch foods to assess the total dietary acrylamide intake.

After 13.3 years of follow-up — from Sept. 17, 1986 to Jan. 1, 2000 — there were 2,649 cases of primary and histologically verified lung cancer in the cohort.

For each 10-microgram per day increment of acrylamide intake, the lung cancer hazard ratio for men was 1.03,with a 95% confidence interval from 0.96 to 1.11.

There was also no trend when male participants were divided into quintiles based on acrylamide intake.

For women, the hazard ratio for each 10-microgram per day increment of acrylamide intake was 0.82, with a 95% confidence interval from 0.69 to 0.96, which was statistically significant at P<0.05.

The hazard ratio for lung cancer for the highest quintile of women (median intake of 36.8 micrograms per day) was 0.45, when compared with the lowest quintile (median intake of 9.5 micrograms per day). That trend, too, was significant, at P=0.01.

The researchers said it might be that acrylamide has a hormonal effect on cancer risk, which might explain the contrast between this study and earlier ones showing an increase in postmenopausal endometrial and ovarian cancer.

On the other hand, other factors could also explain the apparent protective effect in women, according to Lorelei Mucci, Sc.D., and Hans-Olov Adami, M.D., Ph.D., both of Harvard School of Public Health.

In an accompanying editorial, they urged caution in interpreting subgroup analyses that are driven by the data rather than a priori hypotheses.

They also said it is hard to rule out chance in such a finding.

“Perhaps the safer conclusion we can make from the Netherlands study is that the findings do not support a positive association between acrylamide intake from diet and risk of lung cancer,” they concluded.

The study was supported by the Dutch Food and Consumer Product Safety Authority and the Dutch Cancer Society. The researchers reported no conflicts.

Primary source: Journal of the National Cancer Institute

Source reference:

Hogervorst JGF, et al “Lung cancer risk in relation to dietary acrylamide intake” J Natl Cancer Inst 2009; 101: 651-662.

Additional source: Journal of the National Cancer Institute

Source reference:

Mucci LA, Adami, HO “The plight of the potato: Is dietary acrylamide a risk factor for human cancer?” J Natl Cancer Inst 2009; 101: 618-21.

SEATTLE, May 5 — Italian multiple sclerosis patients treated with mitoxantrone (Novantrone) developed leukemia at up to 10 times the rate seen in previous studies, researchers reported here.

• Explain to interested patients that the study was conducted in Italy and may not be fully generalizable to U.S. patients.
• Explain that the adverse effects described in this study occurred in a relatively small number of patients. Point out that the balance of risks and benefits is different for each patient, such that mitoxandrone may still be an appropriate choice for some patients.
• Note that the study was published as an abstract and presented orally at a conference. These data and results should be considered preliminary until published in a peer-reviewed journal.

In a retrospective study of patients treated in 35 Italian hospitals, leukemia developed in 7.4 multiple sclerosis patients per 1,000 treated, according to Vittorio Martinelli, M.D., of University Vita-Salute in Milan, Italy.

Earlier studies of the drug in multiple sclerosis patients had reported leukemia rates of 0.7 to 2.5 per 1,000 patients, Dr. Martinelli said.

But he noted that simply avoiding mitoxantrone is not necessarily a simple way to dodge leukemia risk, as the drug is frequently a last-resort treatment for MS patients.

Still, this and other side effects of mitoxantrone “should be carefully considered against the potential benefit,” he said at a press briefing to announce the results.

“On one side, we have the risk of the disease with a progressive course, which has a high risk to develop significant impairment and disability for the patient. On the other side, we have the risk related to the treatment. We all know there is no treatment without any adverse event,” Dr. Martinelli said.

Mitoxantrone is best known as an anticancer drug. It is approved for treating leukemia, as it suppresses rapidly dividing lymphocytes, B cells, and macrophages.

In 2000, it was approved by the FDA for treating multiple sclerosis, including the relapsing-remitting and primary and secondary progressive forms. However, the drug is less popular for these conditions in the U.S. than in Europe, said Dr. Martinelli.

In addition to the previously known risk for acute leukemia, the drug is also cardiotoxic and causes neutropenia with an associated risk of infection. It carries a boxed warning about these effects.

The study examined records of all patients with multiple sclerosis treated with mitoxantrone since 1999 at the participating hospitals. Inclusion criteria included a minimum of one treatment cycle and one year of follow-up.

A total of 2,854 patients were identified, of whom 21 developed acute leukemia, with eight deaths.

Dr. Martinelli said the incidence rate per month of treatment was 0.16.

He said the dose appeared related to the leukemia risk. Patients developing leukemia had received a mean of 8.6 treatment cycles and a mean total dose of 82.4 mg/m², compared with 7.2 cycles (P<0.05) and 62.9 mg/m² (P<0.009) among patients without leukemia.

However, it’s not clear whether ongoing treatment will increase or decrease the chances of developing leukemia, he said. “We do not know the duration of the period of risk,” he said.

In light of the apparent dose-relationship, he concluded, treatment with relatively low doses of mitoxantrone “could be considered.”

Lily Jung, M.D., of the Swedish Neuroscience Institute here, said the findings weren’t suprising since the drug does carry a warning about secondary leukemia. But the numbers were “frightening,” she declared.

Even so, the study probably won’t have a big effect on U.S. clinical practice because the drug is seldom used there, she added.

“The advent of Tysabri (natalizumab), even with the risk of PML (progressive multifocal leukoencephalopathy), has pushed mitoxantrone down to the very bottom of the list of drugs we would think about,” Dr. Jung said.

She said the drug is most commonly prescribed for aggressive forms of multiple sclerosis. “We were telling patients that the risk [of leukemia with mitoxantrone] was about one in 400,” she said.

The Italian study’s figure of about one in 135, she said, “is pretty dang significant. . . . It puts mitoxantrone in an even more difficult competitive position.”

External funding for the study was not reported. Dr. Martinelli reported relationships with Biogen Dompe, Merck Serono, Bayer-Schering, Teva, and sanofi-aventis. Other investigators in the trial reported relationships with Farmades and Novartis. Dr. Jung reported no potential conflicts of interest.

Primary source: American Academy of Neurology

Source reference:
Martinelli V, et al “Incidence of acute leukemia in multiple sclerosis patients treated with mitoxantrone: a multicenter retrospective study” AAN Abstract LB3.001.

Agents used to treat anaemia in cancer patients, that work by stimulating red blood cell production, also increase mortality. The increased risk of death associated with these drugs should be balanced against their benefits in cancer patients. These are the conclusions of an Article in this week’s edition of The Lancet, written by Dr Julia Bohlius, University of Bern, Switzerland, and Professor Andreas Engert, University of Cologne, Germany, and colleagues.

These drugs, called erythropoiesis-stimulating agents (or ESAs), reduce the need for red blood cell transfusions and could improve quality of life for patients with cancer. However, they have been reported to increase the risk of heart attack and stroke, and might also stimulate tumour growth. Uncertainty remains about whether and how these drugs affect survival; their safety has been discussed repeatedly at hearings of the US Food and Drug Administration and the European Medicines Agency. The authors did a meta-analysis of 53 cancer trials featuring almost 14,000 patients to establish the effect of ESAs on mortality. They assessed mortality during the active study period* and during the longest available follow-up.

The researchers found that 1530 patients died during the active study period and 4933 died overall. ESAs were associated with a relative increase in mortality during the active study period of 17%. When an analysis was done of only cancer patients receiving chemotherapy (38 trials, 10,441 patients), the relative increase in mortality attributable to ESAs was 10%. The type of anticancer treatment given did not make a difference to outcomes.

The authors say: “The findings of this individual patient data meta-analysis show that erythropoiesis-stimulating agents increase mortality in all patients with cancer, and a similar increase might exist in patients on chemotherapy… In clinical practice, the increased risks of death and thromboembolic events should be balanced against the benefits of treatment with erythropoiesis-stimulating agents, taking into account each patient’s clinical circumstances and preferences. More data are needed for the effect of these drugs on quality of life and tumour progression, and meta-analyses similar to this one will address these questions.”

Source
The Lancet

LITTLE FALLS, N.J., May 6 — The FDA gave bevacizumab (Avastin) fast-track approval for the treatment of glioblastoma patients who have been unresponsive to prior therapy, according to drugmaker Genentech.

The accelerated approval followed two pilot studies showing that it improved response rates in patients with glioblastoma.

One study, AVF3708g, included 167 patients with glioblastoma that had progressed after initial treatment with temozolomide and radiation. Patients were randomized to either bevacizumab alone or bevacizumab plus irinotecan.

Tumor responses were observed in 26% of the 85 patients treated with bevacizumab alone. Median duration of response was 4.2 months.

In a separate, single-arm study, NCI 06-C-0064E, about 20% of the 56 patients treated with bevacizumab had response rates, and median duration of response was 3.9 months.

Common adverse events included infection, fatigue, headache, high blood pressure, diarrhea, and nose bleeds.

Others included bleeding, hemorrhage, wound-healing complications, gastrointestinal perforation, and posterior leukoencephalopathy syndrome.

Gastrointestinal perforation occurred in 0.3% to 2.4% of patients. Bleeding occurred up to five times more frequently in patients taking bevacizumab, according to Genentech.

The company warned that the drug should not be initiated for at least 28 days following surgery, and until the surgical wound is fully healed.

Two deaths may have been associated with adverse events, including one retroperitoneal hemorrhage and one neutropenic infection.

Related Article(s):

• Bevacizumab Gets FDA Panel’s Nod for Glioblastoma Multiforme

The commonly used prescription statin drugs may have a protective effect in the prevention of liver cancer and lead to a reduction in the need for gallbladder removals, according to two studies published in Gastroenterology. As millions of Americans use statins each day to help lower their cholesterol and risk of heart disease, researchers are learning of the beneficial effects these drugs may have on gastrointestinal disorders. Gastroenterology is the official journal of the American Gastroenterological Association (AGA) Institute.

Statins Benefit Diabetics at High Risk of HCC

Statin use is associated with a significant reduction in the risk of hepatocellular carcinoma (HCC), or liver cancer, among patients with diabetes, according to a new study in Gastroenterology.

“Our study provides the first indication of a cancer preventive effect for statins specific to HCC,” said Hashem B. El-Serag, MD, MPH, of the Baylor College of Medicine and lead author of the study. “While these findings need to be confirmed in future studies, we are hopeful that further research continues to show the beneficial effect of statins for liver cancer prevention in patients with diabetes.”

HCC is a highly fatal malignancy that has been increasing in several regions of the world, including the U.S. Experimental as well as indirect human data suggests that statins exert a beneficial action, reducing the progression of HCC.

Researchers undertook an epidemiological study in a large cohort of diabetics, whose risk of HCC was higher than average, to characterize the relationship between statin use and HCC and other liver disease. The team examined 1,303 cases and 5,212 controls; the mean age was 72 years. Ninety-nine percent were men and 13 percent were African Americans. A significantly smaller proportion of cases (34.3 percent) had at least one filled prescription for statins than controls (53.1 percent).

The research team found a significant inverse association between having statin prescriptions filled and the risk of developing HCC. There was a trend toward stronger risk reduction with longer and more frequent statin prescriptions. The risk reduction observed with statins ranged between 25 percent and 40 percent. Reduced HCC risk was similar, whether the prescriptions were for simvastatin or any other statin dispensed.

Statins May Reduce Risk of Gallbladder Removal Surgery

The use of statins appears to reduce the risk of cholecystectomy, surgical removal of the gallbladder, in women, according to a new study in Gastroenterology.

Gallstone disease is a common abdominal condition in developed countries and is a major cause of digestive disease leading to hospital admissions. In the U.S., more than 800,000 cholecystectomies are performed each year.

Researchers examined the relationship between statin use and the risk of cholecystectomy in a cohort of U.S. women participating in the prospective Nurses’ Health Study. Participants biennially reported their health history, including incidence of gallstone disease and whether they had undergone cholecystectomy.

Researchers conducted a retrospective analysis of statin use through data collected in 2000 to define use from 1994 forward, and a prospective analysis for general lipid-lowering drugs from 1994 to 2004. In the statin analysis, the researchers ascertained 2,479 cases of cholecystectomy during 305,197 person-years of follow-up. The multivariate relative risk for current statin users, compared with nonusers, was 18 percent. In the analysis of general cholesterol-lowering drugs, researchers ascertained 3,420 cases of cholecystectomy during 511,411 person-years of follow-up. Compared with nonusers, the multivariate relative risk for current users of general cholesterol-lowering drugs, mostly statins in this cohort, was 12 percent. Among diabetic women, duration of current statin use was correlated with risk of cholecystectomy. Compared with statin nonuse, the relative risk for current statin use of two or more years was 75 percent.

“Further study, particularly among diabetics, is warranted to evaluate the associations of longer durations of statin use and specific types of statins with risk,” said Chung-Jyi Tsai, MD, of the University of Kentucky Medical Center and lead author of the study. “Our results should have implications for additional clinical, epidemiological and mechanistic research.”

Source:
Alissa Cruz

American Gastroenterological Association

In the U.S., more than 180,000 women are diagnosed with invasive breast cancer each year. Many of these women will undergo mastectomy surgery that will result in disfiguring scars because they are unaware of the availability of skin-sparing mastectomies and did not ask their surgeons about this treatment option. Skin-sparing mastectomy is a surgical technique to remove cancerous breast tissue by using the same minimal and judiciously placed incisions used by plastic surgeons for elective breast surgery.

Despite the availability of skin-sparing mastectomies, a recent California study published in The American Surgeon found that more than one-third of board-certified breast surgeons surveyed still regularly use the archaic practice of cutting across the whole breast, resulting in unnecessarily disfiguring scars even after breast reconstruction.

“Amidst the shock and anxiety of a breast cancer diagnosis, many women and some physicians consider the appearance of the breasts of secondary importance and not worthy of serious consideration compared to the treatment of cancer,” said Joel Aronowitz, M.D., Clinical Chief of Plastic Surgery at Cedars Sinai Medical Center and founder of the Breast Preservation Foundation, a non-profit organization dedicated to increasing awareness and educating women and their caregivers about skin-sparing mastectomy.

“We know that skin sparing and old style transverse mastectomy techniques are equal in effectiveness as cancer treatments. Therefore, every woman has a right to be informed about choices in mastectomy surgery that improve the cosmetic appearance of the breast and be able to consider all options before embarking on major surgery that will impact their overall quality of life.”

The skin-sparing technique uses a simple, small, circular incision around the edge of the nipple area. The surgeon leaves all or most of the overlying breast skin, preserving the natural skin envelope that can be filled with an implant or with a patient’s own fat tissue from another part of the body. This skin-sparing technique is appropriate for women whose breast cancer does not invade the skin of the breast and particularly when immediate reconstruction is planned.

Millions of women have benefited from elective breast surgery by plastic surgeons over the past 60 years to correct congenital deformity and improve size and shape to enhance women’s lives. Great strides have been made in the understanding of breast surgery and now the medical profession is beginning to apply these advances to one of the most dreaded of operations - mastectomy.

Today, effective mastectomy can be performed with far better cosmetic results. Since new breast cancer cases are among the highest rates ever recorded and breast cancer survival rates are also on the rise it is necessary for patients and their physicians to consider what treatment options will positively affect the patients’ overall health, healing and quality of life, post cancer.

As the senior author in The American Surgeon study and founder of the Breast Preservation Foundation, Dr. Aronowitz hopes to also persuade the general surgery community to use plastic surgery principles for placement of incisions for biopsy and mastectomy procedures.

“Increased use of these modern, reconstructive surgery concepts will result in a decreased use of standard, centuries old ‘cut across the chest’ incisions causing severe disfigurement and long-lasting emotional distress for cancer patients. These are the most modern aesthetic techniques and principles that can be applied with the same rigor as is given to the treatment of cancer, and combined can result in a more satisfying outcome,” Dr. Aronowitz added.

For more information about skin-sparing mastectomies, breast cancer survival and the Breast Preservation Foundation, please visit http://www.BreastPreservation.org.

Source
Breast Preservation Foundation

TORONTO, May 12 — Despite treatment, women diagnosed with cervical intraepithelial neoplasia (CIN) remain at higher risk for a recurrence of the disease or invasive cervical cancer, an international team of researchers said.

• Explain to interested patients that this study found that cervical intraepithelial neoplasia (CIN) treatment does not rule out the prospect of recurrent disease or even invasive cervical cancer.
• Caution that the finding is based on a retrospective cohort analysis and needs to be confirmed.

In a retrospective cohort study, the risk of a subsequent diagnosis of CIN2/3 was associated with the initial diagnosis, age at diagnosis, and treatment method, according to Joy Melnikow, M.D., of the University of California Davis, and colleagues.

Importantly, the rate of invasive cervical cancer was about six times higher among women with a previous diagnosis of CIN than among those without abnormal cytology, Dr. Melnikow and colleagues said online in the Journal of the National Cancer Institute.

“We now have a much more clear idea of the risks of recurrent abnormal cells and invasive cervical cancer over time after treatment of these cells,” Dr. Melnikow said in a statement.

The researchers studied records of 37,142 women treated for CIN 1, 2, or 3 from Jan. 1, 1986, through Dec. 31, 2000 from the British Columbia Cancer Agency cytology database. They linked those records with cancer registry and vital statistics data.

The women were treated with cryotherapy, loop electrosurgical excision procedures, cone biopsy, or laser vaporization or excision.

The so-called CIN cohort was compared with 71,213 women with normal cytology and no CIN diagnosis. All the women in the study were followed until Dec. 31, 2004.

In the first six years after treatment, Dr. Melnikow and colleagues found, the cumulative rate of CIN 2/3 was:

• 14.0% for women originally treated for CIN 3
• 9.3% for women treated for CIN 2
• 5.6% for women treated for CIN 1

Rates of CIN 2/3 were higher for those diagnosed with CIN 3, compared with those who had a lower stage of disease. They were also higher for women diagnosed when they were 40 or older and for those treated with cryotherapy.

After six years, the annual rates of CIN 2/3 were less than 1%, regardless of original diagnosis, and comparable to rates seen among the comparison cohort, the researchers said.

The overall incidence of invasive cancer per 100,000 woman-years was 37 in the CIN cohort, compared with 6.0 in the comparison group.

The same three factors were also associated with increased risk:

• Women treated with cryotherapy, compared with other modalities, had an odds ratio for cancer of 2.98 (CI 2.09 to 4.26).
• Those whose initial diagnosis was CIN 3 (compared with CIN 1 or 2) had an odds ratio of 4.10 (CI 2.70 to 6.22).
• Women 40 or older had an odds ratio of 1.75 (CI 1.12 to 2.74) compared to younger women.

“These data may help inform that treatment discussion, because we know more about how age and different treatments appear to influence risks,” Dr. Melnikow said.

The study was limited by its retrospective design, the researchers said. Also, they were unable to account for changing treatment patterns over the study period.

The findings suggest the need for long-term surveillance of women with a diagnosis of CIN even after treatment, according to Edward Wilkinson, M.D., of the University of Florida College of Medicine in Gainesville, Fla.

In an accompanying editorial, Dr. Wilkinson said the results “support evidence that active surveillance has value in identifying the majority of the high-grade CIN lesions and cervical carcinomas.”

One implication of the study, he said, is that some apparently recurrent CIN may be persistence of disease, rather than a true recurrence.

“In the CIN 3 group,” he said, “the possibility of a persistent lesion, rather than a true recurrence of a new lesion, is supported by the finding that the majority of women with lesions that were found during surveillance after therapy were found within the first two years after therapy.”

The study was supported by the National Cancer Institute. The researchers reported no conflicts. Dr. Wilkinson reported financial links with Merck and Guided Therapeutics.

Primary source: Journal of the National Cancer Institute

Source reference:

Melnikow J, et al “Cervical intraepithelial neoplasia outcomes after treatment: Long-term follow-up from the British Columbia Cohort Study” J Natl Cancer Inst 2009; 101: 721-28

Additional source: Journal of the National Cancer Institute

Source reference:

Wilkinson EJ “Women with cervical intraepithelial neoplasia: requirement for active long-term surveillance after therapy” J Natl Cancer Inst 2009; 101: 696-97.

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