An investigational vaccine directed against 4 types of human papillomavirus (HPV), including the 2 responsible for 70 percent of all cervical cancers (types 16 and 18), reduced their incidence and any HPV-related diseases by 90 percent compared with placebo, researchers reported last week. The findings are the latest in a string of successful studies testing HPV vaccines.
The phase II randomized, double-blind, placebo-controlled study of the quadrivalent HPV vaccine evaluated 552 women from the United States, Europe, and Brazil aged 16 to 23. Participants were randomized to receive the vaccine or a placebo three times over 6 months. They were followed for 2 ½ years, with a primary endpoint of reduction in the combined incidence of persistent HPV types 6, 11, 16, and 18 infections and related diseases, which included precancerous conditions such as cervical intraepithelial neoplasia (CIN).
"The study was not originally powered to assess vaccine efficacy for the disease endpoints of each HPV type separately," wrote Dr. Luisa Villa and colleagues in the paper, released April 6 as an early online publication by The Lancet Oncology. "However, the fact that all three women with external genital lesions and all three with CIN were in the placebo group is encouraging in terms of protection against these endpoints."
Merck, which manufactures the vaccine and funded this study, has already begun a phase III trial of the vaccine, which will test only the lowest of the three doses used in the phase II study. NCI also is leading a phase III HPV vaccine trial in Costa Rica testing a similar vaccine manufactured by GlaxoSmithKline.
The risk of developing rectal cancer after radiation treatment for prostate cancer is low. But, compared with men whose prostate cancer is treated with surgery alone, those treated with external radiation, with or without surgery, have a nearly two-fold increased risk of rectal cancer 5 or more years after treatment. These study results by Dr. Nancy Baxter of the University of Minnesota Medical School and colleagues appear in the April issue of Gastroenterology.
The results are based on a retrospective cohort study using Surveillance, Epidemiology, and End Results (SEER) registry data between 1973 and 1994 collected from men with nonmetastatic prostate cancer and no previous history of colorectal cancer. Among those who received radiation, there was a 1.7 hazard ratio of developing rectal cancer, but no increased risk in other areas of the colon that had less exposure to the radiation.
Because the overall rates of rectal cancer in both the surgery and radiation groups were low - 5.1 and 10 per 1,000, respectively - the authors note that these findings do not indicate needed changes in prostate cancer treatment. Dr. Baxter noted that more targeted treatment, such as conformal radiation, may lower risk to the rectum. The article recommends that men who have radiation therapy for prostate cancer receive endoscopic evaluation for rectal cancer beginning 5 years after treatment.
Dr. C. Norman Coleman, chief of NCI's Radiation Oncology Branch, noted that a variety of risk factors, and the rates of success, complications, and late effects, should be considered in treatment decisions, and that the lack of information about overall survival in the study is a minor limitation. "Even so, these findings show the importance of a team approach to prostate cancer treatment," he said, noting that primary care clinicians and subspecialists "are all critical in the long-term cancer follow-up to help minimize adverse long-term consequences and improve patients' survival and quality of life."
There is a direct correlation between the minimal improvements seen in 5-year survival rates of patients with soft-tissue sarcomas in certain age groups and poor participation by patients in the same age groups in sarcoma treatment clinical trials, researchers reported last week. In an early online release of a study to be published in Cancer, researchers from the University of Texas M.D. Anderson Cancer Center, the Children's Oncology Group, and NCI showed that, during the study period, the smallest improvements in survival for patients with bone and non-Kaposi's soft-tissue sarcomas were seen between 15 and 45 years of age. This correlated directly with the lowest age-related participation rate in NCI-sponsored sarcoma clinical treatment trials.
Further evidence supporting a cause-and-effect relationship can also be found, the authors argue, by study data showing that the strongest age-related improvement in Kaposi's sarcoma (KS) survival occurred in an older age range, which correlated directly with increases in KS treatment trial participation. "There was a statistically significant, age-dependent correlation between survival improvement and clinical trial participation rates, whether or not the type of sarcoma evaluated had a rate decline in young adults (non-KS soft-tissue sarcomas and bone sarcomas) or a peak (KS)," the study's lead author, Dr. Archie Bleyer, wrote.
The study analyzed data from NCI's SEER program on more than 38,000 young adults diagnosed with sarcoma between 1975 and 1998 and correlated it with data on more than 3,200 sarcoma patients entered into NCI-sponsored clinical trials between 1997 and 2002. "There are no easy solutions to the accrual dilemma," the authors conclude. They noted encouragement, however, by the overall increase seen in cancer treatment trial participation by those over 45 years old and recent progress with increasing accrual in treatment trials for patients with sarcomas.
A common treatment for anemia in cancer patients effectively reduces the need for blood transfusions and enhances hematologic response, according to a new meta-analysis, but the data do not clearly show better survival or fewer adverse events. Erythropoietin is a red blood cell stimulator naturally produced by the kidneys, and human recombinant forms can be manufactured as drugs.
In 27 randomized controlled trials conducted between 1985 and 2001, 3,287 patients with a confirmed malignancy took a form of the drug or served as case controls. The meta-analysis of these trials showed that patients receiving the drug were a third less likely to need a blood transfusion. Among all patients, including those with a low hemoglobin level who did need a transfusion, those taking the drug were more likely to have a hematologic response to treatment.
Though the data suggested, but were inconclusive, that overall survival was improved, two additional large randomized controlled trials including more than 1,200 patients found survival to be worse among patients treated with erythropoietin.
The possible harmful effects are an important question, said Andreas Engert and colleagues in the April 6 Journal of the National Cancer Institute, because there is "strong and consistent" evidence that treatment with human recombinant erythropoietins works to reduce the need for blood transfusions and improve response rates to other cancer therapies.
The first study to examine dietary patterns and pancreatic cancer risk shows no significant link between the two. The findings of Dr. Dominique Michaud of the Harvard School of Public Health and colleagues appear in the April 6 Journal of the National Cancer Institute.
Pancreatic cancer is the fourth-leading cause of cancer mortality in this country, but only a few environmental risk factors for the disease have been identified. These include cigarette smoking, diabetes, and obesity. To determine if a link exists between cancer risk and individual dietary components, the researchers analyzed data from two prospective cohort studies, the Health Professional Follow-Up Study and the Nurses' Health Study. Both studies collected demographic and diet information through self-reported participant questionnaires; information on pancreatic cancer was obtained from death records and pathology reports.
The researchers classified participants' diets into two categories: prudent - characterized by vegetables, legumes, fruit, whole grains, fish, and poultry - and western - characterized by red and processed meats, refined grains, French fries, high-fat dairy products, sweets and desserts, and high-sugar drinks. Those who followed the prudent diet had healthier lifestyles overall, but even after controlling for cigarette smoking, exercise, and history of diabetes, there was no link between either diet category and the risk of pancreatic cancer. The authors state that "a different dietary model may be required to understand the underlying mechanism that ties diabetes to pancreatic cancer risk. Alternatively, dietary patterns earlier in life, which we are not able to capture in these cohorts, may be a more relevant exposure."
Researchers have identified a genetic mutation shared by three blood disorders. It occurs in a gene called JAK2 and may permanently activate an enzyme - a tyrosine kinase - involved in the proliferation of blood cells. The defect was found in patients with polycythemia vera (PV), essential thrombocythemia (ET), and myeloid metaplasia with myelofibrosis (MMM).
Two research teams working independently made the discovery. Dr. Tony Green of Cambridge Institute for Medical Research, and colleagues found the JAK2 mutation in 71 of 73 PV patients, 29 of 51 ET patients, and 8 of 16 patients with MMM, according to results published March 19 in The Lancet.
A team led by Dr. Gary Gilliland of Brigham and Women's Hospital in Boston found the JAK2 mutation in 74 percent of PV patients, 32 percent of ET patients, and 35 percent of MMM patients, according to a study published online March 24 in Cancer Cell. The study included 347 patients.
"At this point all we know is that the mutation is common in people with these diseases," said Dr. Stephanie Lee of Brigham and Women's Hospital. "There is evidence that the mutation can cause some of the biologic findings, but we can't say yet that it's the cause of the diseases."
A third study, published early online on March 24 in Nature, found the JAK2 mutation in more than 80 percent of patients with PV. The three blood diseases, which affect about 100,000 people in the United States annually, are known as myeloproliferative disorders.