NCI Cancer Bulletin: A Trusted Source for Cancer Research NewsNCI Cancer Bulletin: A Trusted Source for Cancer Research News
July 13, 2004 • Volume 1 / Number 28 E-Mail This Document  |  Download PDF  |  Bulletin Archive/Search  |  Subscribe

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Cancer Research HighlightsCancer Research Highlights

SELECT Recruits African Americans

The final enrollment figures for the Selenium and Vitamin E Cancer Prevention Trial (SELECT), the largest-ever prostate cancer prevention trial, boast 35,534 participants - more than 3,000 above the accrual goal. As reported in the April 20 NCI Cancer Bulletin, enrollment for SELECT - funded by NCI and coordinated by the Southwest Oncology Group - was closed to accrual about 2 years ahead of schedule.

Approximately 15 percent of SELECT participants are African American. "That is a significant accomplishment," said Dr. Lori Minasian, chief of the Community Oncology and Prevention Trials Research Group in the NCI Division of Cancer Prevention. Because African American men frequently develop prostate cancer at an early age, their eligibility age for the study was dropped from 55 to 50. And in fact, one-third of African American SELECT participants are between 50 and 55. "Opening accrual to younger African American men was a key element in recruiting so many participants from this population," Dr. Minasian said.

Both general and targeted recruitment mechanisms proved effective. For one national event, called "SELECT Sunday," SELECT sites worked with predominantly black churches across the country to educate their parish-ioners about prostate cancer and how to enroll in SELECT. Trial leaders also took advantage of local and national media. "It was heartening that so many men volunteered to participate in this study," remarked Dr. Minasian.

COX-2 Inhibitor Studied in Pancreatic Cancer

Patients with advanced pancreatic cancer may receive some benefit with minimal toxicity from a combination regimen that includes a COX-2 inhibitor, according to the results of a small pilot study by Italian researchers. In the study, published in the July 1 Cancer, 17 patients with progressive advanced pancreatic ductal adenocarcinoma (PDAC), who had received gemcitabine-based chemotherapy, were given continuous treatment with the COX-2 inhibitor celecoxib (Celebrex) and protracted intravenous 5-fluorouracil (5-FU). Of the 16 patients for whom there were results that could be evaluated, 2 had partial responses (23 and 68 weeks, respectively) and 2 had stable disease (10 weeks and 13 weeks, respectively). The overall response rate was 12 percent. Median time to disease progression was 8 weeks and median overall survival was 15 weeks.

PDAC has proven to be resistant to chemotherapy, lead author Dr. Michele Millela of the Regina Elena National Cancer Institute in Rome, wrote. Whereas bolus administration of 5-FU in patients with metastatic, advanced pancreatic cancer has shown to be relatively inactive, continuous 5-FU combined with COX-2 inhibition appears to be "feasible and demonstrates encouraging preliminary activity even in a population of chemotherapy- pretreated patients with far-advanced PDAC." In the study, they noted, "treatment-related toxicity was minimal and manageable, making this combination very attractive in an essentially palliative setting."

PSA Velocity and Prostate Cancer Treatment Outcome

PSA velocity - the rate at which prostate-specific antigen (PSA) levels rise - has a direct relationship to mortality from the disease, according to a study published in the July 8 New England Journal of Medicine. The prospective study by researchers at Harvard Medical School, the University of Connecticut, and Washington University School of Medicine in St. Louis followed 1,095 men for a median of 5.1 years and focused on whether men at risk for death from prostate cancer after radical prostatectomy can be identified using information available during the year before diagnosis.

Measuring PSA blood levels is the current standard for monitoring a man's status/risk of prostate cancer. A cutoff point is used to determine whether further screening is necessary; levels between 0 and 4 are considered normal while levels 20 and higher are considered extremely elevated. "The vast majority of men with prostate cancer present with a nonpalpable tumor and come to medical attention because of an elevated or rising level of PSA," the study authors report.

Men followed in this study who had annual PSA velocities greater than 2.0 nanograms per milliliter (ng/ml) had a higher risk of death from prostate cancer than those with scores of 2.0 ng/ml or less. The scientists also found that initial PSA velocities greater than 2.0 ng/ml remained significantly associated with prostate cancer mortality regardless of pathological reports from prostatectomies. However, they caution that although PSA velocity is linked with prostate cancer death, the initial Gleason score, clinical tumor stage, and PSA level must also still be considered important risk factors.

Late Cardiac Effects in Childhood Cancer Survivors

Use of the free-radical scavenger dexrazoxane (Zinecard) may protect children with acute lymphoblastic leukemia (ALL) from cardiac damage associated with doxorubicin (Adriamycin), University of Miami researchers reported in the July 8 New England Journal of Medicine. Doxorubicin is a component of highly effective treatments for children with ALL, the most common malignancy in children. However, it has also been associated with late cardiac effects, including congestive heart failure, as well an increased risk of death from cardiac causes.

In the study, 206 children newly diagnosed with high-risk ALL were randomized to treatment with only the standard multiagent protocol for ALL, which includes doxorubicin, or to standard treatment plus an infusion of dexrazoxane 30 minutes before receiving doxorubicin. Patients' troponin T blood levels - a sensitive and specific biomarker for cardiac injury - were measured at the time of diagnosis and at various points until the end of therapy. While 50 percent of the children in the chemotherapy-only arm of the study had elevated troponin T levels, only 21 percent of the children who received dexrazoxane showed an increase. Dexrazoxane appeared to have no impact on the chemotherapy's short-term effectiveness.

Long-term follow-up on dexrazoxane's effects is still needed, cautioned Dr. Malcolm Smith, associate branch chief for pediatrics in NCI's Cancer Therapy Evaluation Program and Dr. Noreen Aziz, program director in NCI's Office of Cancer Survivorship. "Additional data are needed to demonstrate that dexrazoxane has no effect on the antileukemia activity of doxorubicin and can be used in the treatment of children with ALL without fear of compromising their overall survival," Dr. Smith said. Long-term follow-up and a recently completed NCI-sponsored trial that evaluated dexrazoxane in more than 500 children with T-cell ALL, he added, should help determine dexrazoxane's optimal role.

HPV May Play Role in Head and Neck Cancer

Head and neck squamous cell carcinomas (HNSCCs) that harbor human papillomaviruses (HPV) have a different pattern of genetic changes than tumors without HPV. These patterns suggest that HPV may play a role in the development of HNSCC, according to Dr. Boudewijn Braakhuis and colleagues at the VU University Medical Center in Amsterdam in the July 7 Journal of the National Cancer Institute.

Previous studies have suggested that HPV may play a role in the development of HNSCCs, and HPV DNA has been detected in the tumors of 10-20 percent of HNSCC patients. To find a possible mechanism by which HPV might cause HNSCC, researchers looked at HPV DNA and RNA and genetic alterations in the tumors of 143 HNSCC patients. HNSCCs with transcriptionally active and inactive HPV DNA had different genetic patterns that support the idea that HNSCCs can be subdivided into two distinct categories and that HPV infection is involved in the early development of some HNSCCs. "Our results are consistent with the hypothesis that HNSCCs develop by two different etiologies: one driven by exposure to environmental carcinogens (e.g., tobacco and alcohol) without HPV involvement and the other involving infection with transcriptionally active [HPV]," the authors wrote.

In an editorial, researchers from the University of Texas M. D. Anderson Cancer Center noted that "understanding how the [HPV] viral proteins interact with cellular proteins and/or DNA in host cells may allow us to design strategies to block malignant transformation."

Carcinogenic Food Ingredient Studied

Researchers have discovered a possible mechanism by which acrylamide - a chemical by-product of processing common foods, such as breakfast cereals and french fries - causes cancer in mice. They also found a similar mutagenic mechanism at work in human bronchial tissue exposed to the chemical and its metabolite, glycidamide.

In a study in the July 7 Journal of the National Cancer Institute, Dr. Ahmad Besaratinia and his colleagues at the City of Hope National Medical Center in Duarte, Calif., reported on the effects of acrylamide and glycidamide on specific genes in mouse cells and in human bronchial epithelial cells. They found that acrylamide and glycidamide, in particular, bind to the DNA, forming adducts at similar specific locations in each of the genes studied. These DNA adducts, which were more common when the cells were treated with glycidamide, coincided with the locations of specific gene mutations in both the mouse and human cell models.

The authors report, "…glycidamide is largely responsible for the mutagenicity of acrylamide." The doses used in the study "might seem too high to be achieved by human dietary exposure alone," they acknowledged. "However, the ever-presence of human exposure to acrylamide on a daily basis makes these estimates somehow more tangible if not achievable. From a public health standpoint, these findings reiterate the need for reconsidering the presence of acrylamide in the human diet and the environment."