Preventive Health Exams May Lead to Cancer Screenings

new report by researchers at the University of California, Davis (UCD), shows that health plan members who receive regular preventive exams are more likely to undergo screening for colorectal, breast, and prostate cancers. The UCD researchers, led by Joshua Fenton, presented their findings in the March 26 issue of 

	The researchers evaluated 64,288 people age 52 to 78 who were enrolled in a Washington State health plan from 2002 to 2003. This population included 39,475 enrollees eligible for colorectal cancer screening, 31,379 women eligible for breast cancer screening, and 28,483 men eligible for prostate cancer screening. The researchers divided the patients into two groups—those who had a preventive health exam or general physical during the two-year period and those who did not. About half of the patients had a preventive health exam from 2002 to 2003.

	After controlling for factors that influence cancer screening rates, such as patient demographics and historical use of medical care, the researchers found that patients who received general health exams were significantly more likely to undergo cancer screening. Men and women who had a general checkup were more than three times as likely as the others to receive colorectal cancer screening, and men were three times as likely to be tested for prostate cancer.

	The corresponding difference was smaller in women eligible for breast cancer screening—about 74% of women who had general health exams got screened as compared to about 56% of women who did not have general checkups. This is because the Washington State health plan “has a longstanding, innovative breast cancer screening program that operates independently of primary care,” Fenton told 

. Women receive mailed reminders about mammography and can schedule mammograms without a physician’s referral. “This may diminish the impact of a physical on mammography in this population,” he said.

	In addition to reinforcing the value of health plan coverage for regular wellness visits, these results should provide a significant lesson to doctors and patients. Some doctors have questioned the value of regular check-ups, Fenton said, but check-ups may give them time to think about prevention and recommend screening tests. In comparison, the study suggests that visiting the doctor only when ill does not have the same effect. “Doctors may simply be too busy to be effective advocates of prevention when they’re taking care of acute or chronic illness,” Fenton said.

Canine Cancer Vaccine Being Investigated for Use in Humans

    First therapeutic vaccine approved by FDA in either animals or humans

joint research effort between one of the nation’s leading cancer centers and a major veterinary hospital has yielded a DNA-based therapeutic vaccine to treat melanoma in dogs. Researchers hope the breakthrough will open the door for treatment in humans as well.

	The vaccine recently received conditional approval from the United States Department of Agriculture (USDA), making it the first therapeutic cancer vaccine approved in the United States to treat cancer in either animals or humans.

	“Both humans and dogs develop this cancer in exactly the same way,” said Dr. Jedd D. Wolchok, an oncologist at New York’s Memorial Sloan-Kettering Cancer Center, who handled the human arm of the laboratory research. “By conducting trials in humans and in animals that live in the same surroundings as humans, there can be a synergy that we hope will result in improved cancer treatment for all.”

	With the USDA’s conditional approval, the vaccine will be marketed for veterinary use while additional safety and efficacy tests are conducted.

	Dr. Philip Bergman of New York’s Animal Medical Center—just blocks away from Memorial Sloan-Kettering&mdash;conducted the vaccine trial in dogs. Dogs in the clinical trial had longer lifespans, even those with advanced-stage melanoma. In dogs, melanoma often starts in the mouth or paws and spreads rapidly, with death often occurring within one to five months once it has spread beyond the primary site. In contrast, the median survival time for dogs in the vaccine therapy group was more than one year.

	“Historically speaking, treatment of oral melanoma with surgery, radiation, or chemotherapy has not been very effective,” Dr. Berman said.

	The novel vaccine will also be delivered in a new way. It will be administered to dogs via Canine Transdermal Device through the skin instead of a traditional needle. The delivery mechanism was developed by Vical Incorporated and Bioject.

	From a business standpoint, the USDA’s conditional approval of the vaccine also represents a breakthrough for veterinary pharmaceutical maker Merial, a joint venture of Merck & Co., Inc. and sanofi-aventis. Both Merck and sanofi-aventis have been aggressively seeking ways to increase their investment in biotech in recent years, with mixed results.

	Melanoma, the most serious type of skin cancer, is primarily caused by overexposure to UV light and can be deadly if not diagnosed and treated early.

                                                                                         — Diane West

Antirejection Drug Shows Promise In Preventing Lung Cancer in Smokers

    Drug already approved for organ, bone marrow and cardiac stent recipients slows the development of cellular changes associated

drug normally used as an antirejection agent in organ and bone-marrow recipients is showing early clinical promise in the prevention of lung cancer in smokers.

	The drug, rapamycin, was shown to block the activity of Akt and mTOR, proteins found in lung cells which, when activated, are associated with precancerous changes. Nicotine and its carcinogenic byproduct, NNK, kick these two proteins into gear, making smokers susceptible to lung cancer. Rapamycin targets mTOR and blocks it from activating, potentially preventing the cells lining the walls of the lungs from becoming precancerous and developing into malignant tumors.

	“By exploring methods of chemoprevention via agents such as rapamycin, we may be able to further reduce lung cancer risk,” NCI director John E. Niederhuber, MD, said.

	In the study, conducted by the National Cancer Institute and published in the April issue of 

, one group of mice injected with NNK received rapamycin one week after exposure to the tobacco-specific carcinogen, while another group was given rapamycin six months after exposure. Mice given rapamycin after one week showed a 90 percent decrease in the number of tumors they developed compared to the other group. Early rapamycin recipients also demonstrated a 74 percent decrease in the size of tumors they did develop and their cancer cells showed fewer abnormalities. Lung tumors which developed in mice, which were given their first dose of rapamycin six months after exposure to NNK shrank, but the rate of tumor cell growth remained unchanged.

	Whether rapamycin can prevent lung cancer in cigarette smokers remains to be seen. “The critical question is whether this approach would be safeand effective in smokers at high risk of developing lung cancer,” NCI’s Dr. Phillip Dennis said. “Given that rapamycin is relatively inexpensive and FDA-approved for other indications, we are designing clinical trails in humans to address these questions and hope to have these answers in the near future.”

                                                                                 — Diane West

Colon Cancer Survival Linked to Number of Lymph Nodes Examined

n analysis of 17 studies found that the more lymph nodes that are removed and examined during surgical treatment of colon cancer, the better the outcome. The study results suggest that removal of the nodes takes away a reservoir for potentially lethal cancer and that knowing how far a cancer has spread leads to better treatment, according to researchers at The University of Texas M.D. Anderson Cancer Center.

	“The importance of adequate lymph node evaluation is not a new concept, but the data have never been evaluated in a systematic fashion such as this before,” noted lead author, George Chang, MD, assistant professor in the department of surgical oncology at M.D. Anderson. “The important message is that surgeons need to adhere to the principles of cancer surgery that are already in place. But, the surgeons are not the only ones responsible for adequate lymph node evaluation; the pathologist must find the

	lymph nodes within the resected specimen.

	“There are many factors that are at play, but the surgeon and pathologist both appear to be important variables in lymph node recovery rates. This is an important issue that potentially impacts not only prognosis but treatment decisions.”

	The results of this study should help efforts to consider a minimum number of lymph nodes that are extracted and examined during the surgery, continued Dr. Chang. “Surgeons do not decide how many lymph nodes to remove. Surgeons perform a cancer-directed operation with en bloc resection of the associated colonic mesentery. Within the mesentery are the lymph nodes. Depending on how adequately the mesentery is resected, there will be more or fewer lymph nodes.

	“In a recent evaluation of the SEER registry by Baxter et al, JNCI 97(3):219-25, only 37% of patients had 12 or more lymph nodes evaluated,” Dr. Chang added. Surgeons sometimes leave nodes because less mesentery is removed than should be. Another reason is that some surgeons believe that the identification of lymph node metastasis was only prognostic, therefore there is no need to remove all of the lymph nodes once metastatic lymph nodes are identified, according to Dr. Chang.

	One of the 17 studies examined, a national clinical trial that enrolled more than 3,200 patients to look at the effects of chemotherapy on colon cancer recurrence after surgical resection, demonstrated a 14% increase in five-year survival if more than 20 lymph nodes were examined, compared with less than 11 nodes in patients with Stage II cancer. The survival advantage was even greater—23%&mdash;in patients with Stage IIIA and IIIB cancer if more than 40 nodes were evaluated, compared with less than 11 nodes.

	All but one study of Stage II cancer showed the same association between the number of nodes evaluated and improved outcome. Also, four of six studies of more advanced cancer showed similar associations, Chang said.

	“This tells us,” Dr. Chang pointed out, “that surgeons and pathologists involved in the care of colon cancer patients should make every effort to improve their collection and evaluation of lymph nodes.”

	Because all of the studies examined were observational, the researchers asserted that they cannot definitively say increasing the number of lymph nodes examined leads to improved survival. Only a randomized, controlled clinical trial, ethically impossible to do, would be able to make such a definitive statement, the researchers explained.

Combined Therapies Improve Breast Cancer Survival

omen with early-stage breast cancer who are given a combination treatment of chemotherapy and tamoxifen have a higher survival rate compared to women who receive only tamoxifen, according to two new studies published in the April 4 

Journal of the National Cancer Institute (JNCI)

. The studies also showed that there were no additional benefits from a combination of ovarian suppression and tamoxifen.

	“These results are important for oncologists and health professionals, because they support current research initiatives to evaluate anti-estrogen strategies in addition to tamoxifen in premenopausal women who avoid chemotherapy or [women] with preserved ovarian function after chemotherapy,” the study’s chief investigator, John Yarnold, who is professor of clinical oncology at the Institute of Cancer Research in Sutton, England, told 

	Treatment with tamoxifen, chemotherapy or ovarian suppression individually is known to increase the survival rate in early-stage breast cancer patients. In 1992, the Adjuvant Breast Cancer Trials were initiated to assess the additional benefits of combined therapies. The studies published in 

 are the results of two international randomized clinical trials, the ABC Chemotherapy (CT) trial and the ABC Ovarian Ablation or Suppression (OAS) trial, that were undertaken by Yarnold, professor of clinical trials Judith Bliss, and their colleagues at the Institute of Cancer Research.

	The two randomized, controlled phase III trials included a total of 3,854 women with early-stage breast cancer. All of these patients were treated with tamoxifen for five years.

	In the ABC (CT) trial, about half of 1,991 women between the ages of 26 and 81 were randomly assigned to receive chemotherapy while the rest did not. Of the 619 premenopausal women in this group, 244 received ovarian suppression. Bliss and her colleagues found that chemotherapy in combination with tamoxifen led to modest improvements in relapse-free and overall survival. They also found that patients younger than 40 years benefited less from chemotherapy than those who were between 40 and 49 years old. Moreover, the benefit was higher for premenopausal women who did not receive ovarian suppression.

	For the ABC (OAS) trial, nearly half of the 2,144 premenopausal women were randomly assigned to receive ovarian suppression while the others did not. Some of the patients also received chemotherapy. The research team found that neither relapse-free nor overall survival was affected by adding ovarian suppression to the tamoxifen treatment of early-stage breast cancer. However, the results pointed to a possible benefit of adding ovarian suppression for a small group of women less than 40 years of age who have ER-positive tumors. This was especially true when the patients were not receiving chemotherapy.

                                                                                                                                                                — Prachi Patel-Predd

Articles

News items featured in this month's issue: 1) Preventive Health Exams May Lead to Cancer Screenings     by Prachi Patel-Predd 2) Canine Cancer Vaccine Being Investigated for Use in Humans    by Diane West 3) Antirejection Drug Shows Promise In Preventing Lung Cancer in    Smokers by Diane West, and more

By Querida Anderson, Prachi Patel-Predd, Nick Rose, Diane West,

Articles

News Reports: May 2007