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Researchers Find that Head and Neck Cancers May Be Different Diseases

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Different risk factors for head and neck cancer have been identified by researchers at Johns Hopkins Kimmel Cancer Center, raising the possibility that they are different forms of these diseases.

Head and neck tumors caused by the human papillomavirus (HPV) were generally associated with sexual behaviors and smoking marijuana, rather than tobacco and alcohol. It was also found that people with the viral-linked cancer were mostly white, younger, married, and college-educated with income of $50,000 or more. Those not attributable to HPV were associated with tobacco, alcohol and poor oral hygiene, most generally listed as the causes of head and neck cancer. The findings are to be published in the March 12 issue of the Journal of the National Cancer Institute.

"Our results indicate that HPV-positive and HPV-negative head and neck cancers have different risk-factor profiles and should be considered two distinct diseases," says Maura L. Gillison, M.D., Ph.D., an associate professor of oncology and epidemiology at Hopkins. "They just happen to occur in the same place."

HPV infection has been seen in up to 72% of patients, and is associated with the development of some neck and head cancers, mostly in the upper throat and back of the tongue. Gillison noted that the incidence of HPV-linked cancer has nearly doubled over the past 30 years, and that head and neck cancer patients with HPV-positive tumors are mlore responsive to treatment and survive longer than HPV-negative patients.

According to Gillison, the American Joint Committee on Cancer is now considering incorporating HPV status in its guidelines for determining clinical stages of head and neck cancer.

For this study, 240 patients at the Johns Hopkins Hospital with head and neck squamous cell carcinomas were studied between 2000 and 2006, to identify HPV-positive or negative tumors. All study participants completed a computerized interview that asked questions about their risk factors.

Source: Journal of the National Cancer Institute, March 12, 2008

Increased Risk of Breast Cancer Recurrence Tied To High Levels of Estrogen

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Women whose breast cancer returned after treatment had almost twice as much estrogen in their blood than did women who remained cancer-free, according to a newly published study.

The study’s lead author, Cheryl L. Rock, Ph.D., a professor in the Department of Family and Preventive Medicine at the University of California, San Diego, said that high levels of estrogen—which lead to the initial development of breast cancer—could be associated with an increased risk of recurring cancer.

"While this makes sense, there have been only a few small studies that have looked at the link between sex hormones in the blood and cancer recurrence," she said. "This is the largest study to date and the only one to have included women taking agents such as tamoxifen to reduce estrogen’s effect on cancer growth."

"What the results mean for women who have already been treated for breast cancer is that they should do as much as they can to reduce estrogen in their blood, such as exercising frequently and keeping weight down," she added. "Taking anti-estrogen drugs like tamoxifen may not completely wipe out the hormone’s effect in women who have high levels of estrogen."

The Women’s Healthy Eating and Living Study (WHEL) provided participants for the breast cancer study, a dietary intervention trial that monitored 3,088 women treated for breast cancer but cancer-free when recruited for the study. Subjects were placed in two groups—one that ate a " normal" healthy diet, one that ate extremely large amounts of fruits, fiber and vegetables. After 7 years, participants were checked for breast cancer, which was about the same for each group. Researchers interpreted the findings to mean that a normal diet that incorporates the U.S. Food and Drug Administration guidelines for recommended amounts of fruits and vegetables is sufficient.

In the current study, 153 WHEL participants whose cancer had recurred were matched with 153 participants who remained cancer-free. These pairs were alike in terms of tumor type, body size, age, ethnicity, use of chemotherapy and other variables. Two-thirds of the participants were using tamoxifen, Rock said.

When they enrolled, researchers tested the women’s blood for concentrations of the steroid hormones estradiol (the primary human estrogen) and testosterone. They analyzed different forms of estradiol and testosterone in the blood, such as how much was bound to transport proteins (such as to the sex hormone binding globulin, or SHBG) and how much was "free" circulating and able to enter a cell.

The study was published in the March issue of Cancer Epidemiology, Biomarkers and Prevention, a journal of the American Association for Cancer Research.

Lung Cancer Patient Response to Treatment May Be Predicted by Biomarkers

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Researchers at UCLA’s Jonsson Center, led by Dr. Steven Dubinett, have discovered biomarkers capable of predicting the response to a combination treatment by Celebrex and Tarceva by patients with advanced non-small cell lung cancer.

It is believed that these findings may help oncologists avoid prescribing conventional treatments that don’t work, in favor of drugs to which they know patients will respond.

In 2008 more than 213,000 Americans will be diagnosed with lung cancer, and of these some 160,000 will die. If further studies confirm the findings of this first study, said Dr. Steven Dubinett, a professor of pulmonary and critical care medicine and senior author, this personalized drug therapy would offer a much-needed alternative therapy. "We need good predictors of response to targeted therapy in lung cancer so individual patients receive the specific therapy that targets the particular molecular abnormalities of their tumors," he said.

The Phase 1 dose-escalation study of the drug combination surveyed a group of patients for whom all other treatments had been unsuccessful. The tumors in 50% of the patients decreased by more than 30%, or had tumors that did not grow—described as stable disease.

When the UCLA team analyzed tumor, blood and urine samples to find out why some patients did so well, they found several biomarkers that could help identify patients likely to respond to the combination Celebrex and Tarceva therapy. The answer appeared to be in the levels of certain proteins in the patients’ blood: Dubinett said that changes in these proteins may help explain the potential benefit of Celebrex in making the tumor cells more vulnerable to Tarceva.

Cycloxygenase-2 (COX-2) is an enzyme that makes cancer cells resistant to death, and causes resistance to drugs like Tarceva, allowing the cancer to grow.

Dr. Dubinett and his team found that if they inhibited the COX-2 pathway, they could restore the sensitivity of lung cancer tumor cells to Tarceva. The samples from Phase 1 patients showed that patients with low levels of MMP9 before treatment responded best to the combination therapy.

If these findings are confirmed in larger studies, in the future that protein biomarker could be used to place patients into groups with patients having low blood levels of MMP9 receiving the Celebrex and Tarceva therapy and responding. A larger, multi-site Phase 11 study of 10 patients is now under way, to confirm if there is a connection between tumors that express the proteins named in the Phase 1 study and a response to combination treatment.

"This study cold determine whether these biomarkers can be used in the future before treatment to select the patients likely to respond," said Dr. Dubinett.

The findings of the study were published in the February 1, 2008 issue of the Journal of Thoracic Oncology.

Source: University of California Los Angeles (UCLA), Health Sciences

Hormonal Components in Some Dietary Supplements May Promote Progression of Prostate Cancer

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A recent study by researchers at UT Southwestern Medical Center concludes that hormonal components in over-the-counter dietary supplements may actually accelerate the progression of prostate cancer, at the same time decreasing the effectiveness of anti-cancer drugs.

The study, published in the January 11, 2008 issue of Clinical Cancer Research, strongly advises patients to tell their doctor if they are taking any herbal or hormonal dietary supplements. It is also recommended that the use of such supplements is routinely documented as part of the patient’s health assessment.

"Physicians need to ask their patients not only about the prescription drugs they may be taking, but—perhaps even more importantly—about the over-the-counter drugs and supplements, which may have a profound impact on certain health conditions," said Dr. Claus Roehrborn, chairman of urology at UT Southwestern and one of the study’s authors.

The research commenced when two UT Southwestern patients developed aggressive prostate cancer mere months after starting daily use of the same dietary supplement—one for muscular development, the other for sexual enhancement. When Dr. Roehrborn and Dr.Shariat, a resident in urology and the study’s lead author, and their colleagues analyzed the product (not named in the study) they found that the label listed ingredients not present, misrepresented the concentrations of the ingredients that were present, and did not list all the steroid hormones in the product.

Hormone analysis showed the presence of testosterone and estradiol, a sex hormone. Testing of the product’s effect on human prostate cancer-cell lines revealed that the product was a more potent stimulator of cancer-cell growth than testosterone. Use of the anti-cancer drug bicalutamide, in increasing concentrations, proved ineffective.

"Bicalutamide is an oral nonsteroidal anti-androgen used to treat prostate cancer," Dr. Shariat said. "The fact that this supplement caused the drug to be less effective is very troubling." The researchers filed an adverse event report with the Food and Drug Administration, which in turn issued a warning letter to the manufacturer, who withdrew the product from the market.

"Unlike prescription and over-the-counter drugs, the law does not require nutritional supplements to undergo pre-market approval for safety and efficacy," Dr. Shariat said. "The current FDA regulatory system provides little oversight or assurances that dietary supplements will have predictable pharmacological effects or even that product labels provide accurate information for consumers."

It is estimated that 42% – 69% of U.S. adults use dietary supplements, at an estimated cost of $34 billion. People often use supplements in the belief that these natural products are safe and drug-free. The sale of androgenic steroids meanwhile is increasing exponentionally, with 2004 sales U.S. expenditures on testosterone supplements totalling an estimated $425 million.

"Given that testosterone supplements are in high demand, there is significant concern that supplements, in addition to the one we evaluated, may pose an urgent human health risk," Dr. Shariat said.

Researchers from Baylor College of Medicine in Houston also contributed to the research.

"The current FDA regulatory system provides little oversight or assurances that dietary supplements will have predictable pharmacological effects or even that product labels provide accurate information for consumers."

Infertility and Testicular Cancer Linked, Says Study

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University of California, San Francisco researchers have found that men with a history of infertility have a markedly increased risk of subsequently developing testicular cancer. The purpose of the study was to assess testicular cancer in infertile men usingna cohort study methodology.

More than 51,000 couples, drawn from 15 California infertility centers during the period 1965 and 1995, were evaluated for infertility. Male subjects’ medical records were linked to the California Cancer Registry, the cumulative Surveillance Epidemiology and End Results Registry (SEER) for the State of California. Cancers preceding infertility were excluded from analysis, and the incidence of testicular cancer in this cohort was compared to age-matched men from the general population.

The study found that men from infertile couples were 60% more likely to develop testicular cancer than other men (standardized incidence ratio 1.695% confidence interval 1.2 to 2.2). This risk was relatively constant across all age strata.

Source: UroToday

Improved IMRT Cancer Treatment Reduces Radiation Exposure to Healthy Tissue

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Recent studies by researchers at Montefiore Medical Center have shown that improved IMRT (intensity modulated radiation therapy) treatment provides far better patient care than standard radiation procedures because it safeguards healthy tissue surrounding cancerous tumors.

"We compared treatment techniques for cancers of the lung, abdomen, pelvis and head and neck, and were able to quantify just how much better IMRT was for patients in the studies than conventional radiation therapy," said Shalom Kalnicki, MD, chairman of the Department of Radiation Oncology at Montefiore.

Using the new IMRT technology, oncologists can now deliver thousands of precisely focused beams of radiation that follow the exact contours of a cancerous tumor. Today’s standard therapy uses cross-firing X-ray beams, and is not nearly as accurate.

A study of lung cancer patients showed that the average dose of radiation to the esophagus is reduced by 20 percent, and reduced by 30 percent to the area of the lung most critical for breathing.

"By developing and carrying out a tailor-made IMRT treatment plan for each patient, we reduced significantly the chance of having radiation beams harm healthy lung tissue and therefore impaired breathing," said Dr. Kalnicki.

In another study, Montefiore researchers used IMRT technology to treat patients with pancreatic cancer. Radiation dosage to the nearby kidneys was reduced by 38 percent, and radiation dosage to the normal bowel was also reduced by 38 percent.

A third Montefiore study used image guided adoptive planning, another advanced form of IMRT, to treat complex-shaped head and neck cancers.

The salivary glands, mandible, nerves and oral cavity lining were dramatically safeguarded using this method, resulting in significant improvement of patient quality of life.

Source: Montefiore Medical Center

FDA Approves Bristol-Meyers Squibb’s Drug Ixempra for Breast Cancer Treatment

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The U.S. Food and Drug Administration has approved Ixempra (ixabepilone), a new anti-cancer treatment, for use in patients with metastatic or locally advanced breast cancer who have not responded to certain other cancer drugs.

Ixempra is indicated as monotherapy for the treatment of metastatic or locally advanced breast cancer in patients whose tumors are resistant or refractory to anthracyclines, taxanes, and capecitabine.

"This approval is important because it provides certain patients with a new chemotherapy option in instances where other drugs have failed," said Douglas C. Throckmorton, M.D., deputy director of the FDA’s Center for Drug Evaluation and Research.

The FDA evaluated Ixempra under priority review, completing its assessment of the drug’s safety and effectiveness in six months.

Ixempra was approved for use in combination with another cancer drug, capecitabine, in patients who no longer benefit from two other chemotherapy treatments. These prior treatments included an anthracycline (such as doxorubicin or epirubicin) and a taxane (such as paclitaxel or docetaxel).

Ixempra was also approved for use alone in patients who no longer benefit from an anthracycline, a taxane and capecitabine.

According to the American Cancer Society, about 180,000 new cases of breast cancer are diagnosed each year in the United States. Metastatic breast cancer is the most advanced stage of breast cancer and has the potential to spread to almost any region of the body.

Ixempra has been shown to bind to cancer cell microtubules, which are structures within cells that help to support and shape them. Microtubules also play a role in cell division.

The safety and efficacy of Ixempra in combination with capecitabine were evaluated in 752 patients in a randomized clinical trial comparing the combination to capecitabine alone. This combination therapy demonstrated improvements in delaying cancer progression or death compared to capecitabine alone.

The safety and efficacy of Ixempra administered alone were evaluated in a study of 126 patients. Clinically significant tumor shrinkage occurred in 12 percent of the patients.

Ixempra’s significant side effects included peripheral neuropathy (numbness, tingling or burning in the hands or feet) and bone marrow suppression. Other commonly observed toxicities included constipation, nausea, vomiting, muscle paint, joint pain, fatigue and general weakness.

Women taking Ixempra should avoid taking drugs that are strong inhibitors of CYP3A4, one of the enzymes that metabolizes Ixempra.

Ixempra should not be taken by women who have had severe allergic reactions to drugs that contain Cremophor or its derivatives, or by women who have baseline bone marrow suppression determined by low white blood cell or platelet count.

The combination of Ixempra and capecitabine should not be given to patients with moderate or severe liver impairment due to the increased risk of toxicity and death.

Ixempra is administered by intravenous infusion. It is distributed by Bristol-Meyers Squibb Company, Princeton, New Jersey.

Source: FDA (October 22, 2007)

Three Alcohol Drinks Per Day May Significantly Increase Breast Cancer Risk

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It isn’t the type of alcohol but the quantity which increases a woman’s risk of contracting breast cancer.

In fact, the increased breast cancer risk from drinking three or more alcoholic drinks a day is similar to the increased breast cancer risk from smoking a pack of cigarettes or more a day, according to Kaiser Permanente researchers Yan Li, MD, PhD and Arthur Klatsky, MD.

"Population studies have consistently linked drinking alcohol to an increased risk of female breast cancer, but until now there has been little data, most of it conflicting, about an independent role played by the choice of beverage type," said Klatsky, who is presentied these findings on Sept. 27 at the European Cancer Conference (ECCO 14) in Barcelona, Spain.

The study found there was no difference between wine, beer or spirits in the risk of developing breast cancer. Even when wine was divided into red and white, there was no difference. However, when researchers looked at the relationship between breast cancer risk and total alcohol intake, they found that women who drank between one and two alcoholic drinks per day increased their risk of breast cancer by 10 percent compared with light drinkers who drank less than one drink a day. The risk of breast cancer increased by 30 percent in women who drank more than three drinks a day.

"A 30 percent increased risk is not trivial. To put it into context, it is not much different from the increased risk associated with women taking estrogenic hormones. Incidentally, in previous research completed at Kaiser Permanente, we have found that smoking a pack of cigarettes or more per day is related to a similar (30 percent) increased risk of breast cancer," Klatsky said.

Although breast cancer incidence varies between populations and only a small proportion of women are heavy drinkers, Dr Klatsky said that a 30 percent increase in the relative risk of breast cancer from heavy drinking might translate into approximately an extra 5 percent of all women developing breast cancer as a result of their habit.

"Klatsky said that all medical advice needed to be personalized to the individual. "Our findings provide more evidence for why heavy drinkers should quit or cut down."

Source: Kaiser

Obesity linked to increased risk of esophageal cancer

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Writing in the aptly named online journal Gut, Australian researchers have discovered a disproportionate incidence of increased esophageal cancers in overweight individuals.

According to the researchers, those with a "body mass index (BMI) of 40 or more, were six times as likely than those with a BMI of between 18.25 and 25."

Gastric reflux increased the incidence of this cancer 5X, and combined with obesity, the risk increased 15X.

Men 50 years old and younger were particularly vulnerable.

Prostate Cancer Mortality Rate Lower with Surgery Than Other Treatment Options

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Prostate cancer patients who opt for radiation treatment, hormone therapy, observation, or other forms of treatment for localized prostate cancer have a higher rate of death within 10 years than patients who have undergone surgery for prostate cancer, according to a recent Swiss study, published in the Archives of Internal Medicine.

As there have not yet been any notable randomized trials for prostate cancer treatments, treatment decisions are currently strongly influenced by the patient and physicians’ personal perferences and experiences, say the study’s authors.

Researchers used data from the Geneva Cancer Registry to assess all 844 patients diagnosed with localized (not yet spread) prostate cancer in Geneva between 1989 and 1998.

Of those men, 158 received prostatectomy, or surgery to remove all or part of the prostate; 205 had radiation treatment (radiotherapy); 378 chose watchful waiting, which entails active follow-up and treatment if the disease progresses; 72 underwent hormone therapy; and 31 had another type of therapy.

After 10 years, survival rates were 83 percent for those who underwent surgery to remove the prostate (prostatectomy), 75 percent for radiation therapy, 72 percent for watchful waiting, 41 percent for hormone therapy and 71 percent for other treatments.

"At 10 years, patients treated with radiotherapy or watchful waiting had a significantly increased risk of death from prostate cancer compared with patients who underwent prostatectomy," the authors wrote.

The increased mortality associated with radiotherapy and watchful waiting was primarily observed in patients under 70 years of age and in patients with poorly differentiated tumors, or tumors that have certain cellular characteristics and are more likely to spread aggressively.

While the authors recognize that their study can be improved through randomized clinical trials, they noted that "until clinical trials provide conclusive evidence, physicians and patients should be informed of these results and their limitations."

Source: Archives of Internal Medicine  2007;167(18):1944-1950.