Trials in the past decade offer the first evidence that some of the most prevalent cancers in the population are preventable, and a host of ongoing trials are testing new prevention strategies, Peter Greenwald, MD, DrPH, director of the National Cancer Institute's Division of Cancer Prevention, said at the 50th Annual Meeting of the Southwest Oncology Group (SWOG).
SEATTLE--Trials in the past decade offer the first evidence that some ofthe most prevalent cancers in the populationare preventable, and a host of ongoingtrials are testing new preventionstrategies, Peter Greenwald, MD, DrPH, director of the National Cancer Institute'sDivision of Cancer Prevention, said atthe 50th Annual Meeting of the SouthwestOncology Group (SWOG). However,he noted, critical challenges in thefuture will include putting the knowledgegained into practice and ensuringan adequate supply of health care professionalsto implement prevention efforts.
Dr. Greenwald noted that this yearmarks the 23rd anniversary of the CommunityClinical Oncology Program(CCOP), the main mechanism by whichNCI provides funding for clinical cancerprevention trials. The program currentlyhas 3,325 participating physicians, 390participating hospitals, and 56 ongoingcancer prevention and control trials.
Prostate Cancer Prevention
The Prostate Cancer Prevention Trial,conducted among men who had a PSAlevel of 3 ng/mL or lower, found that relative to placebo, finasteride was associatedwith a roughly 25% reduction inthe incidence of prostate cancer of anygrade, but also with a higher incidence ofcancers of Gleason grades 7-10, Dr.Greenwald said. Subsequent investigationsuggested that the latter finding was likelydue to a detection bias related to finasteride-induced shrinkage of the prostateand, therefore, a greater likelihood of hittinga high-grade area of a cancer duringa biopsy. Furthermore, he noted, analysesrestricted to men with tumors ofGleason grades 8-10 showed that amongthose treated with finasteride, the tumorswere smaller and less often had aggressivefeatures.
"Based on this SWOG-led study, wehave the first definitive evidence thatprostate cancer, at least in part, is preventable,"Dr. Greenwald commented. "We also have a unique tissue bank withcontrols that is helping in a major reevaluationof the PSA test, and providinga lead toward understanding, at a biologicallevel, what makes these tumorsaggressive."
He noted that further data on prostatecancer prevention are awaited fromthe Selenium and Vitamin E Cancer PreventionTrial (SELECT), in which menare receiving one or both supplements,or placebos, for 7 years. "It is a wonderfultrial. It is in progress. It is tremendouslywell run and managed," he said.
Breast Cancer Prevention
The Breast Cancer Prevention Trialfound that relative to placebo, tamoxifenwas associated with a nearly 50% reductionin the incidence of breast canceramong women at high risk, Dr. Greenwaldsaid. Further, the Multiple Outcomesof Raloxifene Evaluation (MORE)trial found a 76% reduction in the risk ofinvasive breast cancers with raloxifene(Evista), compared with placebo among postmenopausal women with osteoporosis."These two trials were the main drivingfactor for the decision to initiate theSTAR [Study of Tamoxifen and Raloxifene]trial, the head-to-head comparisonof tamoxifen and raloxifene," he said.
In the recently reported STAR trial,among postmenopausal women, the twodrugs were equally effective in preventingprimary invasive breast cancer,achieving reductions of 40% to 50%,while raloxifene was less effective in preventingnoninvasive breast cancers.
Overall, quality of life did not differbetween treatments; symptom profilesslightly favored raloxifene, whereas sexualfunctioning slightly favored tamoxifen.In terms of adverse events, raloxifene wasassociated with lower rates of thromboembolicevents, endometrial cancer,and cataracts.
"We look forward to two majorevents," Dr. Greenwald commented."First, we think that Eli Lilly is likely tobring raloxifene to the FDA for approvalfor an indication for breast cancer prevention.Assuming that will happen, afterthat, we think it might be useful tohave an education program so thatwomen have a balanced view of the prosand cons, and the options, of preventingbreast cancer in this way."
The second event is a planned head-to-head trial comparing raloxifene withan aromatase inhibitor for breast cancerprevention, he said. This trial, called P-4,should begin within the year if funding isobtained. "We think, in a sense, that havingthese successes will raise the understandingby the public and will directlybenefit the public in a way that shouldhelp us get support for clinical researchof all sorts," he added.
Turning to the future of cancer prevention,Dr. Greenwald discussed worrisometrends in the relative numbers ofoncology patients and oncology professionals.Data from the Surveillance Epidemiologyand End Results (SEER) programsuggest that the number of peopleliving with cancer will roughly doublebetween 2000 and 2050, he noted (seeFigure). At the same time, data from theAmerican Society of Clinical Oncologyshow that the organization currently hasonly about 540 US oncologist membersyounger than 35 years of age, and datafrom the Oncology Nursing Societyproject that the number of nurses nationallywill remain flat or slightly decreaseby 2020.
"So we have a situation of a growingpopulation of cancer patients who stillneed care, even with the best of moderntherapy, and a limited number of professionalsin oncology. It is even a greaterproblem for prevention," he said. "I thinkwe need to . . . figure out how to addresstraining more people to work in this fieldand all of the relevant professions. Wealso need to look toward, as has beendone in cardiology, making stronger tiesto primary care physicians and the otherspecialties we will be working with."
Cancer prevention trials are "here tostay" in the medical setting, and therealso are public health approaches to preventingcancer, Dr. Greenwald concluded, giving a few examples. "One ofthe exciting frontiers is the anti-nicotinevaccines. There are phase II trials inprogress by at least three companies withdrugs that bind the nicotine in an immunologicway that prevents it from reachingthe receptor in the brain," he said.Such vaccines would likely be applied toavert relapses in smokers trying to quit.
Addressing the unfavorable trends inobesity and inactivity that may be contributingto cancer incidence "probablymeans not only working with the healthsector but also with city planners so thatplaygrounds are safe and streets are safefor riding a bicycle," he said.
Turning to use of the anti-HPV vaccineto prevent cervical cancer, he notedthat the vaccine "is certainly going towork, but we are going to have to figureout socially how best to apply it to teenagegirls and maybe others."
Finally, Dr. Greenwald noted that itwill be essential to build cancer preventioninto clinical practice and commendedSWOG members for theirparticipation in clinical trials. "The factthat you are taking part in some of thecancer prevention trials means that asthe results come in, we are a leg up in thediffusion and adoption of the knowledgegained from them," he commented.