Use of cholesterol-lowering drugs called statins reduced the risk of colorectal cancer in adults by 51 percent, researchers from the University of Michigan reported last week at the ASCO annual meeting in New Orleans. The population-based, case-control study compared 1,849 Israeli colorectal cancer patients with 1,959 controls. After controlling for potentially confounding factors such as family history, ethnicity, and aspirin use, the reduction in risk was 46 percent. Statins are the number one selling class of drugs in the United States and two statins, atorvastatin (Lipitor) and simvastatin (Zocor) and are the two top selling drugs, respectively.
The study results, said senior investigator Dr. Stephen B. Gruber, are "very exciting and potentially good news." But despite the study's results, he cautioned, "this is an observational study and should not yet change the standard of care or the indications for statins.
"The findings appear to reinforce findings from several earlier studies. A study published in the June 1 issue of Cancer, for example, showed that 5 years of sustained statin use decreased the risk of breast cancer in postmenopausal women.
As for the mechanism by which statins may reduce colorectal cancer risk, Dr. Gruber noted that several cholesterol-dependent molecular targets are also important cancer genes, including the genes Ras and Rho.
"Cholesterol regulates a lot of cellular proteins, so it's not surprising that [statins] may have diverse effects." His group, Dr. Gruber added, is pursuing the development of a study to examine the impact of statin use on people at high risk for colorectal cancer.
"There is a mechanistic basis for this finding," said Dr. Ernie Hawk of the NCI Division of Cancer Prevention. "We've been waiting to see whether more mature observational data like these would show a preventive benefit. There is potential with these drugs, but these findings are still very preliminary. They need confirmation in additional mechanistic and observational studies, and we need to explore their use in early phase trials before we can really say whether statins will offer any benefit in colorectal cancer risk reduction." NCI is interested in the chemopreventive potential of these agents, Dr. Hawk added, and is pursuing two phase II trials to test whether they can prevent melanoma and colon cancer.
Early results from an international phase III trial show that bortezomib (Velcade), a targeted cancer drug, is more effective than a standard therapy at delaying disease progression in patients with multiple myeloma that has relapsed or become resistant to other treatments. The results, presented at the ASCO annual meeting by the study's principal investigator, Dr. Paul G. Richardson of the Dana-Farber Cancer Institute, were so encouraging that the trial was stopped early and patients on the standard therapy, dexamethasone, were allowed to switch to bortezomib.
Conducted at 94 centers in the United States, Canada, Europe, and Israel, the study enrolled 669 patients with relapsed or resistant multiple myeloma, a disease that kills about 12,000 people per year in the United States.
After a median follow-up of 8 months, disease-free progression was 5.7 months for patients treated with bortezomib versus 3.6 months for dexamethasone. After 1 year, 89 percent of patients in the bortezomib group were still alive, compared with 65 percent of those in the dexamethasone group. To date, there have been 48 deaths in the bortezomib group, compared with 81 among those given dexamethasone.
"Bortezomib is a very promising new targeted agent," said Dr. Wyndham Wilson of the NCI Center for Cancer Research. "However, these results are preliminary, and further studies will be necessary before it will be clear that bortezomib sets a new standard of care for relapsed or resistant multiple myeloma."
A significant risk for thromboembolism was found among children and young adults with sarcomas, according to the results of a study presented this week at the ASCO annual meeting.
The research, conducted by NCI's Pediatric Oncology Branch (POB), reviewed records on 122 consecutive patients treated for sarcoma, ranging in age from 4 to 32 years (median age was 18). There were 23 thromboembolic events (TEEs) recorded, affecting 19 (16 percent) of the patients in the study group. Of those events, 57 percent were detected at presentation, 22 percent during the initial treatment cycle, and 22 percent at recurrence. Incidence rates were higher among patients with metastases (23 percent) compared with those with localized disease (9 percent).
Nearly half (43 percent) of the TEEs were asymptomatic, detected in routine imaging or autopsy. By far, the most common site of thromboses was deep veins of the extremities (43 percent), followed by pulmonary (22 percent), inferior vena cava (17 percent), right atrium (9 percent), and other much less frequent sites.
Previous research had detected high rates of TEEs among adult cancer patients but data on pediatric patients has been limited, explained POB Clinical Director Dr. Alan Wayne. "Thromboembolism is a potentially life-threatening, yet manageable, complication of cancer," he said. "Patients with sarcoma and other types of cancer should be closely monitored. The appropriate use of anticoagulant therapy should decrease morbidity and mortality associated with thromboembolic events."
Three studies presented this week at the ASCO annual meeting showed that the addition of the monoclonal antibody rituximab (Rituxan) to standard treatments for different forms of lymphoma can prolong survival in some instances and improve outcomes such as progression-free survival in others. In a study led by the Eastern Cooperative Oncology Group, the use of rituximab as maintenance therapy following initial chemotherapy treatment in patients with advanced indolent (or slow-growing) non-Hodgkin's Lymphoma (NHL), significantly improved progression-free survival compared with chemotherapy alone. After 4 years, progression-free survival was 58 percent in patients given rituximab versus 34 percent in the chemotherapy-alone group. "The effect of maintenance therapy with rituximab was much more robust than we anticipated," said the study's lead author Dr. Howard S. Hochster of the New York University School of Medicine.
Meanwhile, an 18-country study, dubbed MINT, examined combining rituximab with various forms of a chemotherapy regimen (often referred to as CHOP) as a first-line treatment in patients under 60 with aggressive NHL. Compared with a CHOP regimen alone, the combination approach yielded significant improvements in "time to treatment failure," the study's primary endpoint, explained lead author Dr. Michael Pfreundschuh of Saarland University Medical School in Hamburg, Germany. In addition, at 2 years, overall survival was 95 percent in the combination therapy group and 85 percent in the chemotherapy-alone group.
Lastly, a German research group assessed the effect of adding rituximab to a CHOP chemotherapy regimen for the treatment of a rare, aggressive, and often fatal form of lymphoma called mantle cell. Patients treated with the combination therapy more often experienced complete remission (34 percent versus 7 percent) and were able to stay in remission for longer periods of time (22 months versus 14 months).
The study's lead author, Dr. Wolfgang Hiddemann of the University of Munich, said that all three studies pointed to a paradigm change in the treatment of lymphomas toward combining therapies - and doing so at different points of treatment.
Improvements in overall survival among patients with head and neck cancers were seen in two studies presented this week at the ASCO annual meeting. In one study, the combination of the monoclonal antibody cetuximab (Erbitux) and high-dose radiation therapy nearly doubled survival in patients with locally advanced head and neck cancer. Patients were randomized to high-dose radiation therapy (213 patients) or radiation therapy and cetuximab (211 patients). Median survival for patients in the latter group was 54 months versus 28 months in the radiation-alone group, with a significant survival advantage at 2 and 3 years. The improvement in survival - as well as in locoregional control, the study's primary endpoint - was seen without further exacerbation of the often toxic effects of radiation therapy, said study lead author Dr. James A. Bonner, from the University of Alabama at Birmingham.
A second study found that treating patients with locally advanced head and neck cancer not amenable to surgery with a platinum drug-based chemotherapy regimen that included the drug docetaxel (Taxotere) improved overall and progression-free survival rates compared with the same regimen without docetaxel. Advances in such patients are needed, said the study's principal investigator, Dr. Jan B. Vermorken of the University of Antwerp in Belgium, because 5-year survival rates are below 10 percent, with most patients dying within 18 months. The median progression-free survival for patients on the docetaxel regimen was 12.7 months, compared with 8.4 months for those on standard therapy. Median overall survival was 18.6 months versus 14.5 months.