Childhood Cancer Death Rates Decline

Improvements in the treatment of childhood leukemias have contributed to a decline in cancer death rates among U.S. children and adolescents from 1990 to 2004, researchers from the U.S. Centers for Disease Control and Prevention reported in the December 7 Morbidity and Mortality Weekly Report.

"The good news is that the overall cancer death rates decreased significantly during this period in boys and girls, children and adolescents, most racial and ethnic groups, and all U.S. Census regions," said co-author Dr. Jun Li.

Using data from the National Vital Statistics System, the researchers identified 2,223 cancer deaths among children and adolescents in 2004, compared with 2,457 in 1990. Adjusted for population growth, this translates into 27.3 cancer deaths per million in 2004 versus 34.2 deaths per million in 1990. In 2004, leukemia was the leading cause of childhood cancer deaths, followed by brain and other cancers of the nervous system. Together, these accounted for more than 50 percent of the deaths.

"We really have made a lot of strides in treating leukemias, and this is reflected in the improvements we are seeing," said co-author Dr. Loria Pollack. She noted, however, that children are still dying from these devastating diseases and more progress is needed.

Between 1990 and 2004, death rates for leukemias declined by 3 percent per year, for brain and other nervous system cancers by 1 percent per year, and for all other cancers combined by 1.3 percent per year. Meanwhile, incidence rates for all childhood cancers increased by 0.6 percent per year from 1975 to 2002. Cancer is the fourth-leading cause of death among children and adolescents, after accidents, homicides, and suicides.

The analysis revealed some disparities. Hispanics and non-Hispanics had similar childhood cancer death rates in 1990, but these rates declined more rapidly for non-Hispanics than Hispanics between 1990 and 2004. Lack of health insurance and access to health care may be factors, but differences in tumor aggressiveness, cancer stage at diagnosis, and response to treatment also should be considered, the researchers said.

Mediterranean Diet and Physical Activity Associated with Lower Death Rates

Separate analyses from the NIH-AARP Diet and Health Study indicated significant reductions in the overall death risk for people who adhere to the so-called "Mediterranean diet" as well as among those who engaged in physical activity levels suggested by national exercise guidelines, according to two studies published in the December 10/24 Archives of Internal Medicine.

The NIH-AARP study was developed by an NCI research team that is now part of the Division of Cancer Epidemiology and Genetics (DCEG). The study monitored the health status of more than 500,000 AARP members in the U.S. aged 50-71 from 1995 to 2005 using mailed questionnaires, death records, and tumor registry data.

In the first study, researchers used a 9-point scale to assess adherence among 380,296 healthy AARP members to the Mediterranean dietary pattern, which includes high intake of vegetables, legumes, fruits, nuts, whole grains, fish, higher intake of monounsaturated than saturated fat, moderate alcohol consumption, and low red meat intake. The dietary pattern was associated with a 21-percent decreased risk of all-cause mortality (17 percent for cancer deaths and 22 percent for cardiovascular deaths) in men, and a 20-percent decreased risk of all-cause mortality (12 percent for cancer deaths and 19 percent for cardiovascular deaths) in women. The beneficial effect of the Mediterranean dietary pattern was more pronounced in smokers, especially those with a healthy body mass index.

In the second study, researchers examined the effect of adherence to national guidelines for both "moderate" and "vigorous" physical activity among 252,925 AARP members. Compared with inactive, sedentary respondents, people who engaged in moderate exercise (at least 30 minutes, most days of the week) had a 27-percent decrease in overall mortality, and those who exercised vigorously (at least 20 minutes, three times a week) reduced their death risk by 32 percent.

"Our findings strongly confirm the importance of these national physical activity guidelines," noted study leader Dr. Michael Leitzmann of DCEG's Nutritional Epidemiology Branch. A secondary finding showed that even those individuals who engaged in physical activity at less than the guideline recommendations had a reduced mortality risk.

DCEG is pursuing additional research on physical activity, Dr. Leitzmann added. "We're now drilling down to the effect of exercise on specific forms of cancer. Those impacts may differ from that on total mortality," he said.

Allogeneic Transplant Does Not Increase Survival in High-Risk ALL

In a collaborative clinical trial from the UK Medical Research Council and the U.S. Eastern Cooperative Oncology Group, adult patients with standard-risk Philadelphia-chromosome-negative acute lymphoblastic leukemia (ALL) had significantly increased overall survival after high-dose, chemotherapy-induced first remission followed by allogeneic stem cell transplantation. However, while patients with high-risk ALL had a decrease in the risk of relapse with allogeneic transplantation, their overall survival did not significantly increase, due to the high rate of transplant-related mortality.

"Surprising though it might appear, the high-risk patients benefit less from having a donor than the standard-risk patients in terms of overall survival," state the authors in their paper published online November 29 in Blood. "This is an important finding since there is often a view that high-risk patients should go immediately to allogeneic transplant."

The trial also tested autologous (self) transplantation versus maintenance chemotherapy for patients who did not have a matched sibling donor available for allogeneic transplantation. Unmatched patients who went into remission after the initial high-dose chemotherapy were randomly assigned to receive either autologous transplantation or 2.5 years of maintenance chemotherapy.

Those patients receiving chemotherapy had significantly improved overall survival compared with patients undergoing autologous transplantation, and there was no significant difference in nonrelapse (i.e., treatment-related) mortality between the two groups. However, in an analysis comparing all patients with a donor versus those without a donor, those with a donor had better overall survival rates.

"Sibling donor allogeneic transplant is the treatment of choice for adults with standard-risk ALL in remission providing the greatest chance for a long-term survival. Autologous transplant has a less favorable outcome than consolidation/maintenance chemotherapy for those without a donor," conclude the authors.

Trials Demonstrate Investigational Compound's Chemoprevention Potential

A combination of the investigational compound DFMO with low doses of the anti-inflammatory agent sulindac may be a powerful chemopreventive approach in people at high risk of developing colorectal polyps, researchers reported last week.

The combination of the two drugs significantly decreased the formation of new colon polyps, including advanced polyps, compared with placebo. The 375 participants in the phase III, double-blind, randomized trial all had previously had colon polyps removed.

The results were presented during a session on cancer prevention clinical trials at the American Association for Cancer Research's (AACR) fourth annual Frontiers in Cancer Prevention Research meeting in Philadelphia.

The trial was stopped early, following a recommendation of its Data Safety Monitoring Board, because its primary goals had been met, explained lead investigator Dr. Frank L. Meyskens from the University of California, Irvine. Toxicities - including audiologic toxicities, a concern raised in earlier studies of DFMO - were minimal and similar between the two trial arms.

Results from a subgroup analysis of a different phase III trial investigating DFMO for the prevention of nonmelanoma skin cancer were also presented at the same AACR meeting session, demonstrating a significant protective effect against basal cell carcinoma.

Bortezomib Tested as First-Line Treatment for Multiple Myeloma

At last week's annual meeting of the American Society of Hematology, researchers announced results of several phase III European clinical trials testing the drug bortezomib (Velcade) as a first-line treatment for multiple myeloma. Bortezomib is currently approved in the U.S. as a second-line treatment for the disease.

One multicenter study involved 482 patients who were randomized to receive either a combination of bortezomib and dexamethasone or a combination of vincristine, doxorubicin, and dexamethasone, followed by transplantation with allogeneic stem cells. The results showed that 21 percent of patients who received the bortezomib regimen went into complete disease remission before transplantation, whereas only 8 percent did so in the control group. Of the 404 patients who went on to receive stem cell transplantation, 41 percent in the bortezomib group were in complete remission, compared with 29 percent in the control group.

Another study included 256 patients who were randomized to receive bortezomib, thalidomide, and dexamethasone, or thalidomide and dexamethasone alone. Patients in the test group showed 36 percent complete remission before stem cell transplantation, whereas 9 percent of patients had complete remission in the control group. After stem cell transplantation, the complete remission rates were 57 percent versus 28 percent, respectively.

A third study, named VISTA, involved 682 patients who were ineligible for allogeneic stem cell transplantation. In the test group, which received bortezomib, melphalan, and prednisone, 35 percent of patients went into complete remission, compared with 5 percent in the control group who received melphalan and prednisone alone. The bortezomib group also saw a 40-percent lower risk of death compared with the control group.