“Paradigm Changes from the Prairie”

By: Roscoe F. Morton, M.D., F.A.C.P.

Cancer ultimately affects one in every three Americans. The best hope of cure is early detection and earlier intervention with more effective therapies. Cancer research is the agent of change. It is through research we will achieve more effective and less toxic therapies. When a family member develops cancer, we want their healthcare providers to have the latest and most effective treatment strategies for them. It is medical research that provides us with treatments that have been proven to be effective: evidence-based medicine.

Cancer research is carried out in many venues. On the most fundamental level, there is basic science research which involves molecular biology, chemistry, immunology,pharmacology, pharmocogenomics, genetics, and epidemiology. Translation of this knowledge from the basic sciences to the bedside is the providence of clinical research. The goal of clinical research is to test ideas brought forward by the basic science cancer researchers and apply them in the clinical setting to test their effectiveness. Clinical trials are the research tool by which emerging new therapies are tested against older established treatment to discover which is the more effective and has the least side effects.

Nation-wide approximately 3% of cancer patients participate in a clinical research trial as part of the treatment for their disease. This participation avails them of the latest in cancer treatments and helps clinical researchers develop more effective therapies. These clinical trial participants blaze the trail for those with their disease who will subsequently follow. This is a most important legacy for the next generation Americans: better and more effective treatment for diseases that affect humankind.

Central Iowa is fortunate to have a major clinical research program in cancer medicine. In 1979 the Iowa Oncology Research Association was formed in Des Moines by four visionary physicians. They affiliated their fledgling research group with the Mayo Clinic’s Comprehensive Cancer Center’s cooperative oncology research group: the North Central Cancer Treatment Group (NCCTG).

These visionary physicians, Drs. Louis Maher, Robert Strickler, John Green, and S. Fed Brunk, firmly believed with the Mayo Clinic’s Dr. Charles Moertel that cancer research belonged in the community and should be above medical and hospital politics. Since then, the Iowa Oncology Research Group has grown to include the Iowa cities of Ames, Mason City, Ottumwa, and the surrounding communities they serve. These physicians realized that bringing the latest in cancer treatment to local communities was important as over 90% of cancer patients receive all of their care in their local communities. Overall, the Iowa Oncology Research Association reaches approximately a million Iowans in its catchment area.

The community-based research venue is the ultimate crucible in which to determine if new treatments are more effective than the standard established ones. If the treatment works in Des Moines, Duluth, and Peoria, then it will be effective in any community. Too often new treatments have initially appeared to be promising in small elite groups of patients treated at major cancer centers only to fail when generalized to the average cancer patient. There are multiple reasons for this disparate result with the major one being that the patients in the small trials at academic medical centers often are not representative of the average patient with that cancer. Dr. Charles Moertel of the Mayo Clinic Cancer Center was one of the first to recognize this. Dr. Moertel used the mandate of the National Cancer Act of 1971 to develop a community-based cancer research group: the North Central Cancer Treatment Group (NCCTG). The NCCTG serves many communities and now has over thirty primary research sites in North America, of which one is the Iowa Oncology Research Association consortium of Des Moines, Ames, Mason City, and Ottumwa oncology physicians and hospitals. Like Des Moines, each of the thirty primary research sites also have a number of smaller affiliates

Initially, the Iowa Oncology Research Association was privately funded by small gifts by the Des Moines area hospitals and a few philanthropic individuals. All physician time was donated. In 1983 the Iowa Oncology Research Association successfully competed for a National Cancer Institute designation as a Community Clinical Oncology Program or CCOP. Since then, they have been successful in their re-competition for this research grant funding from the National Cancer Institute. The most recent award is for more than $750,000 per year to fund the research effort in Central Iowa. They are one of 50 designated Community Clinical Oncology Programs (CCOPs) by the National Cancer Institute (NCI) and the National Institutes of Health (NIH).

The Iowa Oncology Research Association’s affiliation with the North Central Cancer Treatment Group (NCCTG) has been a most fruitful relationship, producing paradigm changing research results in three areas of colorectal cancer. The bounty of this research is now saving tens of thousands of lives each year in the United States.

The first major breakthrough was in 1989 when researchers from the NCCTG and the Mayo Clinic Cancer Center reported that the combination of 5-FU chemotherapy and the anti-helmenthic agent levamisole could reduce the risk of recurrent colon cancer by 33% if given to node positive patients after potentially curative surgery. A second clinical trial by this group discovered that patients with rectal cancer at high risk to relapse after potentially curative surgery could reduce their risk of death by 40% with the addition of 5-FU chemotherapy and radiation therapy after surgery. In these two seminal clinical trials, 5% of these pioneering patients were from our Central Iowa communities. The results of these clinical trials have been generalized and are now helping save the lives of countless patients with colon and rectal cancers.

In May 2002 Dr. Richard Goldberg of the Mayo Clinic and Dr. Roscoe Morton of Des Moines reported another paradigm changing treatment for patients with advanced and incurable cancers of the colon and rectum. These investigators, with their colleagues, reported the North American Intergroup Study of several different combinations of chemotherapy. They tested the standard IFL regimen (irinotecan, 5-FU, and leucovorin) of Dr. Leonard Saltz of Memorial Sloan Kettering Cancer Center in New York against the FOLFOX-4 (5-FU, leucovorin, and oxaliplatin) of Dr. Aimery de Gramont of Paris. Drs. Goldberg and Morton demonstrated that the French FOLFOX-4 regimen gave superior control and improved survival for patients with metastatic colon and rectal cancers with less toxicity. This paradigm changing treatment has now been presented by Dr. Goldberg in Orlando, England and Italy and by Dr. Morton in Spain, San Francisco, and San Diego. In August 2002, the Food and Drug Administration used the data of Drs. Goldberg and Morton to approve oxliplatin for the United States market.

In addition to research studies for the treatment of cancer, the Iowa Oncology Research Association is actively involved in the arena of cancer prevention. Currently, we are participating in the National Surgical Adjuvant Breast and Bowel Project’s (NSABP) Breast Cancer Prevention Trial which is comparing the efficacy of tamoxifen (NoveldexÔ) with that of raloxifen (EvistaÔ) in postmenopausal women for the reduction of risk of the development of invasive breast cancer. In an earlier trial by the NSABP, reported in 1998, tamoxifen was shown to reduce the risk of invasive breast cancer by 49% in women at increased risk. Reduction of the incidence of breast cancer is an important strategy in the fight against cancer, as this disease will affect 12.5% of all American women. Individuals interested in participating in a cancer prevention trial may call (515) 244-7586 for more information.

For Caucasian men of 55 years of age or older and African-American males of 50 years or old, the second Prostate Cancer Prevention Trial is available. This randomized trial is comparing selenium, vitamin E, the combination of selenium and vitamin E to placebo to determine if the incidence of prostate cancer can be reduced. This is an important study as prostate cancer will affect 12% of all African-American males and 10% of Caucasian males. Individuals interested in participating in a cancer prevention trial may call the Iowa Oncology Research Association at (515) 244-7586 for information.

In the arena of early diagnosis, the Iowa Oncology Research Association is collaborating with Dr. David Ahlquist of the Mayo Clinic to determine if a polymerase chain reaction (PCR) amplification technique for detecting oncogene products in the stool far earlier that can the guaiac test can detect fecal occult blood. This study is aimed at individual 65 years or older who have not had fecal occult blood testing within the past year or colonoscopy within the past ten years who are undergoing surveillance colonoscopy. Individuals interested in participating in a cancer prevention trial may call (515) 244-7586 for more information.

The Iowa Oncology Research Association and the North Central Cancer Treatment Group appreciate the willingness of the cancer patients of Central Iowa to participate in clinical research trials. The best way a cancer patient can receive the latest in cancer therapy is to participate in a clinical trial. This not only benefits the patient but also helps to benefit one’s fellow human beings by helping researchers discover new and more effective treatments.

Please encourage your patients to participate in cancer clinical trials when they are asked. They can seek information about available clinical trials by calling the Iowa Oncology Research Association office at (515) 244-7586 or visit its web site at http://www.iora.org. The National Cancer Institute’s web page at http://www.cancer.gov/ with its PDQ section is a wealth of peer reviewed information for cancer patients and their families well as their physicians.