ORLANDO, June 5 — A third of patients with metastatic breast cancer receive off-label therapy at some point during treatment, according to a study reported here.

• Explain to interested patients that metastatic breast cancer often is treated with drugs that are not approved for use in breast cancer.
• Explain, however, that few of the study patients received medically inappropriate therapy.
• Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

More than 70% of the drugs used off label lacked evidence to support their use in breast cancer, but these drugs were used in only a small percentage of patients, Sharon Giordano, M.D., of the University of Texas M.D. Anderson Cancer Center in Houston, said at the American Society of Clinical Oncology meeting.

Few patients received what was judged to be medically inappropriate therapy, she said.

“Although off-label drug use is widespread among patients with metastatic breast cancer, the vast majority of patients who received off-label drugs were treated with chemotherapy that was considered appropriate for use in treatment of breast cancer,” Dr. Giordano said in an interview.

Estimates of the frequency of off-label therapy in medical practice range from 21% to 51%. Off-label use of chemotherapy drugs is thought to be widespread, but few studies have examined the issue, particularly with respect to the medial appropriateness of off-label therapy.

The last study to evaluate off-label chemotherapy practices was conducted about 20 years ago and covered cancer in general, not just breast cancer, Dr. Giordano said.

In an effort to develop a knowledge base specific to breast cancer, she and her colleagues analyzed merged data from the NCI Surveillance, Epidemiology, and End Results program and Medicare. They limited the analysis to women ages 65 and older who had a diagnosis of metastatic breast cancer from 1991 to 2002.

Investigators used the DRUGDEX drug compendium to evaluate the appropriateness of off-label therapy.

The study involved 2,082 women. Overall, 34.9% of the patients received at least one off-label therapy. Off-label treatment was least common in patients older than 80 (24.4%) and most common those ages 65 to 70 (37.7%, P=0.004).

Off-label drug therapy became less frequent over time. More than half of the therapy in 1991 (52.4%) was off label. Off-label therapy reached a nadir of 29.7% in 1997, rose to 37.6% over the next two years, and then declined again, accounting for 31.5% of treatment in 2002 (P=0.025).

The frequency of off-label therapy varied geographically, from 42.7% in Connecticut to 12.5% in rural Georgia (P=0.019).

The analysis uncovered off-label use of 36 different chemotherapeutic agents. Used most frequently were vinorelbine (Navelbine), 15.98%; gemcitabine (Gemzar), 8.37%; carboplatin, 7.03%; and mitoxantrone, 6.83%.

All four drugs had supporting evidence for breast cancer.

Dr. Giordano said 71% of the drugs lacked evidence for use in breast cancer, making the use medically inappropriate. However, only 6.7% of the patients received medically inappropriate therapy.

Because the study was limited to women 65 and older, the findings may understate the extent of off-label therapy, the researchers acknowledged.

Dr. Giordano has plans for additional studies of off-label therapy across a spectrum of tumor types and stages. She also hopes to examine off-label use in younger breast cancer patients.

Dr. Giordano and her coinvestigators reported no disclosures.

Primary source: Journal of Clinical Oncology

Source reference:

Dean-Colomb W et al. “Off-label drug use in women with breast cancer” J Clin Oncol 2009; 27(15 suppl): Abstract 1016.

CHICAGO, June 5 — Clinicians might eventually be able to find out whether patients have pancreatic cancer by having them spit into a cup, a researcher said here.

• Explain to interested patients that there is currently no screening test for detecting pancreatic cancer in its earliest stages.
• Explain that pancreatic cancer is usually detected in the advanced stages after it can no longer be surgically resected.
• 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.

James Farrell, M.D., of the University of California Los Angeles, and colleagues, discovered a dozen genes in the saliva of patients with pancreatic cancer that showed different patterns of expression between these patients, those with chronic pancreatitis, and healthy controls.

A panel of four of these genes had the best ability to differentiate between the different groups of patients.

Speaking at Digestive Disease Week, Dr. Farrell said his group’s long-term goal is to develop a screening test for the general population.

But in the short term, he and his colleagues are focusing on high-risk subgroups, including people with a family history of pancreatic cancer and those with cystic neoplasms of the pancreas, which are predisposed to cancer.

In order to make an appreciable difference in the prognosis of patients with pancreatic cancer, Dr. Farrell said, the test would have to be able to detect the disease either in its pre-cancer stages or when the tumor is still resectable.

“It’s still considered that you can, not so much cure those patients, but improve their survival,” Dr. Farrell said.

But pancreatic cancer is rarely detected in its earliest stages, and out of an estimated 42,470 people who will be diagnosed with the disease this year, 35,240 will die, according to the American Cancer Society.

That makes pancreatic cancer the fourth leading cause of cancer death.

Using salivary markers for diagnosing cancer is not a new idea, Dr. Farrell said. Such an approach has been evaluated in ovarian and breast cancers.

To explore whether this would work for pancreatic cancer, he and his colleagues collected saliva from 12 patients with early or locally advanced pancreatic cancer and 12 healthy controls matched for gender, age, ethnicity, and smoking history.

The researchers extracted mRNA and identified 12 genes that were differentially expressed between the two groups.

The use of the genes as biomarkers was assessed in a validation cohort comprised of 30 patients with cancer, 30 with chronic pancreatitis, which has a clinical presentation similar to that of pancreatic cancer, and 30 healthy controls.

The expression of all 12 genes was significantly different between the cancer patients and the controls (P?0.014 for all).

The expression of nine of them was significantly different between the cancer patients and those with chronic pancreatitis (P?0.035 for those nine).

None of the 12 genes had significant associations with oral, lung, or breast cancer — with the exception of one gene and lung cancer — which “basically alludes to the point that the markers that we’re finding appear to be specific for pancreatic cancer,” according to Dr. Farrell.

The individual genes on their own did not have enough discriminatory ability to classify patients as having cancer or being free from disease with areas under the receiver operating characteristic curves (AUCs) ranging from 0.682 to 0.823.

So the researchers looked at combinations of genes and identified panels with AUCs ranging from 0.971 to 0.981 with sensitivities ranging from 90% to 96.7% and specificities ranging from 95% to 100% depending on whether the comparison group was healthy controls, patients with chronic pancreatitis, or all individuals free from pancreatic cancer.

The investigators are currently developing prospective clinical validation studies for these gene panels.

Dr. Farrell reported no conflicts of interest.

Primary source: Digestive Disease Week

Source reference:
Farrell J, et al “Multiple salivary biomarkers for pancreatic cancer detection” DDW 2009; Abstract 964.

At the ends of chromosome are special pieces of DNA called telomeres. Think of it as the little tip that caps off a shoelace. The telomeres send signals to the cells to let them know it’s the end point, not a break that should be repaired.

Over time, as cells reproduce, the telomeres become shorter and eventually no longer do their job. The cells then have a higher risk of mutating into cancer.

But, a new study finds, if the telomere becomes dysfunctional at any point - regardless of shortening - it can trigger a cancer event. The study, by researchers at the University of Michigan Comprehensive Cancer Center, was done in mice generally prone to develop cancer. The mice that also had dysfunctional telomeres were particularly prone to develop the usually ultra-rare adrenocortical cancer. This is the first mouse model to specifically address this rare but lethal type of cancer.

“Usually when telomeres get short, they also seem to get deprotected. No one’s been able to say if it’s the shortening or the deprotection that causes cancer to arise. In this study, we were able to show that deprotection alone, even in the absence of a short telomere, is enough to trigger cancer. This may be a general mechanism of adrenal cancer as well as many other cancers in the body,” says study author Gary Hammer, M.D., Ph.D., the Millie Schembechler Professor of Adrenal Cancer at the U-M Comprehensive Cancer Center.

Results of the study appear in the June issue of Cancer Cell.

The researchers also found that a protein called p53 usually prevents the cancer trigger. P53 is critical to the cell destruction process. When it’s missing, cells replicate uncontrolled, the hallmark of cancer. In this study, the researchers eliminated p53 in the mice and found that the dysfunctional telomeres then tried to repair themselves. This led to breaks in the chromosome, causing scrambled genes and mutations.

“P53 mutation together with telomere dysfunction may be the basis for the genomic changes we see in adrenal cortical cancer and other malignancies,” says study author Tobias Else, M.D., a post-doctoral fellow and Garry Betty Scholar in Adrenal Cortical Cancer Research at the U-M Comprehensive Cancer Center.

Adrenal cancer is extremely rare — about 600 new cases are diagnosed each year in the United States. It is typically diagnosed in late stages when there is nearly no chance of survival beyond five years. Researchers hope that a better understanding of how the disease develops will help lead to new treatments for a cancer type that gets little to no attention and limited research funding.

“This work proves a basic science principle and gives us understanding of how these genetic changes occur to give us this cancer. But it is not just limited to adrenal cancer. Our research started with the adrenal gland, but we saw tumors form in multiple parts of the body. This will be of broader interest to the scientific community,” Else says.

Additional authors: Alessia Trovato, Alex C. Kim, Yipin Wu, David O. Ferguson, Rork D. Kuick, Peter C. Lucas all from the U-M Health System

Funding: Garry Betty Foundation, National Institutes of Health, Sidney Kimmel Cancer Research Foundation

Reference: Cancer Cell, Vol. 15, Issue 6, pp. 465-476

Source:
Nicole Fawcett

University of Michigan Health System