Gloucester Pharmaceuticals announced that results from two studies of romidepsin, its novel, cyclic peptide, histone deacetylase inhibitor under investigation for the treatment of hematologic malignancies, will be presented at the American Society of Clinical Oncology (ASCO) Annual Meeting in Orlando, Florida on Saturday, May 30, 2009.

Poster Q11 #8546 entitled “Pooled analyses of 2 international, multicenter clinical studies of romidepsin in 167 patients with cutaneous T-cell lymphoma (CTCL)” by M Demierre, S Whittaker, Y Kim, E Kim, R Piekarz, M Prince, J Nichols, J Balser, A Prentice and S Bates, describes clinical results from a pooled analysis of two Phase 2 international studies of romidepsin in cutaneous T-cell lymphoma (CTCL).

Poster S13 #8584 entitled “Histone deacetylase inhibitors potently synergize the antineoplastic effects of the proteasome inhibitor bortezomib in mantle cell lymphoma (MCL)” by L Paoluzzi, L Scotto, Seshan and O O’Connor, describes data from a preclinical study of romidepsin in combination with Velcade® (bortezomib) in mantle cell lymphoma (MCL). This study was conducted in collaboration with researchers from the Herbert Irving Comprehensive Cancer Center, College of Physicians and Surgeons, The New York Presbyterian Hospital and Columbia University.

Both posters will be presented during the General Poster Sessions Saturday, May 30, 2009 from 8:00am - 12:00pm ET on Level 2 of West Hall C at the Orlando Convention Center.

About Romidepsin

Romidepsin is a late-stage oncology drug candidate being studied across a range of hematologic malignancies. A registration trial in cutaneous T-cell lymphoma (CTCL) has recently been completed, successfully exceeding its primary endpoint based on overall response rate. A registration trial in a second indication, peripheral T-cell lymphoma (PTCL), is currently enrolling patients. Complete and durable responses were observed in a previous National Cancer Institute trial including both patients with CTCL and PTCL. Numerous other trials are ongoing in additional indications including multiple myeloma. Over 750 patients, to date, have received romidepsin in clinical trials with the most common adverse effects including fatigue, gastrointestinal disturbances and hematologic toxicities. Romidepsin’s cyclic peptide structure is novel among members of a new class of cancer drugs known as histone deacetylase (HDAC) inhibitors. HDAC inhibition has been shown to increase acetylation of histones and other proteins. The downstream effects of HDAC inhibition include growth inhibition, apoptosis, inhibition of angiogenesis and differentiation. Preclinical studies suggest that romidepsin is a pan-HDAC inhibitor and is a potent inhibitor of Class I, Class II and Class IV HDACs. Gloucester Pharmaceuticals retains worldwide rights to romidepsin which received Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) for the treatment of non-Hodgkin’s T-cell lymphomas, including CTCL and PTCL, and Orphan status from the European Medicines Agency (EMEA) for the treatment of both CTCL and PTCL. The FDA has also granted Fast Track status for CTCL and PTCL. A New Drug Application submission for romidepsin in CTCL was accepted by the FDA and a PDUFA is scheduled in November of 2009.

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Gloucester Pharmaceuticals

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CHICAGO, June 1 — More precancerous polyps were found in colonoscopies performed with deep sedation than with milder sedation in which patients remained conscious, a researcher reported here.

• Explain to interested patients that colonoscopies may be performed either with deep sedation or with milder sedation in which the patient remains conscious and able to communicate.
• Explain that this study was retrospective analysis of medical records and therefore a weaker form of evidence than a prospective, randomized trial.
• 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.

Doctors found polyps larger than 9 mm or suspected colorectal tumors found at a 25% higher rate (95% CI 9% to 42%) in patients examined under deep sedation, said Katherine Hoda, M.D., of Oregon Health and Science University in Portland, Ore.

The differences persisted after controlling for age, gender, race, American Society of Anesthesiologists (ASA) class, and clinical site type, Dr. Hoda told colleagues at Digestive Disease Week here.

At a press briefing in advance of her formal presentation, Dr. Hoda said colonoscopists may encounter fewer distractions when patients are deeply sedated and hence do a better job of finding polyps.

But the study design — a retrospective review of nearly 105,000 patient records — could not fully exclude the possibility that patients with higher polyp counts were more likely to receive deep sedation, she pointed out.

She said prospective studies are needed to settle the issue.

Dr. Hoda and colleagues at OHSU analyzed data from the Clinical Outcomes Research Initiative, which collects information on colonoscopies performed at 61 U.S. practice sites.

From 2002 through 2007, the database yielded 101,367 procedures conducted with moderate conscious sedation — typically induced with a benzodiazepine plus fentanyl or another opioid — and 3,501 performed under deep sedation, most commonly with propofol.

Dr. Hoda said these proportions reflect the fact that conscious sedation is the predominant U.S. standard.

Large polyps were found more frequently in patients with deep sedation: 7.2% of such patients had large polyps identified, compared with 6.0% of those with conscious sedation (P=0.01).

The difference remained significant after adjusting for several potential confounding factors available in the database records (OR 1.25, 95% CI 1.09 to 1.42).

But Dr. Hoda said the choice of deep versus conscious sedation is not random in clinical practice.

Patients more likely to pose problems during colonoscopy would preferentially receive deep sedation, and it’s conceivable that such patients would be at higher risk for advanced polyps.

She said the analysis showed ASA scores were higher in patients who received deep sedation, reflecting a greater burden of systemic disease.

But she said the likelihood is that deep sedation genuinely allows better polyp detection.

Patients who remain conscious sometimes report discomfort or otherwise interact with the colonoscopist during the procedure, she said. Time and attention spent on making a conscious patient comfortable may detract from the clinician’s ability to focus on the colonoscopy monitor.

She added that recovery times following deep sedation are typically the same or shorter than after conscious sedation. “Propofol is cleared from the body very quickly,” she said.

A downside, though, is that some centers require that deep sedation be delivered by an anesthesiologist, increasing the procedure’s cost.

The database used in the study did not contain cost information.

Kenneth Wang, M.D., of the Mayo Clinic in Rochester, Minn., said the study provided the first hard data on sedation level as an influence on the effectiveness of detection.

“Nobody has ever really looked at [whether] deep sedation can aid in detecting more polyps,” he said, although clinician efficiency and patient satisfaction has been well documented.

“This will really need to be verified in studies to see if this is actually true. I suspect it probably is,” Dr. Wang said.

“Awake or conscious sedation is exactly that — the patient feels things,” he added. “If you’re trying to remove a polyp and the patient is having some issue with discomfort, you tend not to want to do too much more. Whereas if you have the patient under deep sedation, it wouldn’t surprise me that you could look more carefully around folds, for example, or come in and out of a rather tricky turn.”

No external funding for the study was reported. Dr. Hoda reported no potential conflicts of interest. Dr. Wang reported research funding from AstraZeneca Pharmaceuticals, BARRX Medical, Fujinon, Olympus America, and Spectra Science.

Primary source: Digestive Disease Week

Source reference:
Hoda K, et al “More large polyps are seen on screening colonoscopy with deep sedation compared with moderate conscious sedation” DDW 2009; Abstract 722.

LITTLE FALLS, N.J., June 1 — Taking a break from hormone replacement therapy doesn’t reduce a woman’s chances of having to return for a second screening mammogram, researchers say.

• Explain that brief hormone therapy suspension was associated with small changes in breast density but did not affect overall mammography rescreening rates.

Hormone therapy increases breast density, and abnormal screening mammograms are more common among women with denser breasts, but recall rates were not significantly different between women who didn’t take a break from hormone therapy and those who took one or two months off prior to screening, according to Diana S. M. Buist, Ph.D., M.P.H., and colleagues.

“No evidence supports short-term hormone therapy suspension before mammography,” they reported in the June 2 issue of the Annals of Internal Medicine.

To prevent false positives and avoid recalls, some women take short breaks from using postmenopausal hormone therapy before having mammography.

However, no evidence exists for the efficacy of this practice.

So to test whether one or two months off the hormones decreases mammography recall rates, the researchers looked at 1,704 women ages 45 to 80 who had used hormone therapy at their most recent screening in the Radiological Evaluation and Breast Density (READ) trial.

All of the women were due for mammography and were still using hormones when they were included in the study.

About a third of the women suspended their hormones for one month, and another third for two months before getting a mammogram. The rest, who continued on their hormone regimen, served as the control group.

The researchers found no significant differences between recall rates among the three groups — 11.3% in the continuous-hormone group, 12.3% in the one-month suspension group, and 9.8% in the two-month suspension group.

They also found that decreases in percentage of breast density were not statistically significant, although they trended downward — 0.1% for no suspension, ­-0.9% for one-month suspension, and -1.5% for two-month suspension.

However, women in the groups who stopped hormone treatment experienced increased menopause symptoms.

The linear trends of increased recall were seen with increasing percentage of density, signaling that “density is still an important factor influencing recall rates, but it is likely that change in density needs to be large to have any clinical effect on recall rates,” the researchers said.

“We really hoped to find that a brief break in hormone therapy would lower false-positives and remove unnecessary costs and anxiety by improving mammography,” Dr. Buist said. “We were disappointed to find that it didn’t, but we’ll keep trying to find ways to reduce recall rates for women.”

The researchers noted that their study is limited in that it can only be generalized to women ages 45 to 80 who have used hormone therapy for at least one year.

TThe study was supported by a grant from the National Cancer Institute. The researchers reported no conflicts of interest.

Primary source: Annals of Internal Medicine

Source reference:

Buist DSM, et al “Short-term hormone therapy suspension and mammography recall” Ann Intern Med 2009; 150: 752-65.