Cancer

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Surfing the Net for Cancer related topics to date has yielded little in the way of Canadian content. However, one site whose URL is www.concerningcancer.com manages to fill that void. "Concerning Cancer" has been authored by a Mississauga, Ontario Urologist and is a peer-reviewed discussion of cancers of the prostate, breast, bladder, kidney and testes directed at both patients and physicians with links to related sites chosen for their content and presentation and offering up to date news items. The whole site is available in five languages. Web pages are freely offered to Cancer Support groups and a number are represented there.

Choosing the broadband-oriented path from the home page leads to soft music and rich text with useful illustrations and educational video designed to offer the most pleasing milieu for those starting their search for answers to their questions about these cancers. Based on Canadian guidelines, the site is an attractive option for those physicians engaged in self-education and is a great handout in the office to patients on the Web. We recommend that you visit "Concerning Cancer" soon and leave some words of encouragement in the Guest Book.

91st annual meeting of the American Association for Cancer Research

For the first time, an antisense therapy has been successful in treating a solid tumour in humans. Austrian investigators used a combination of an antisense drug G3139 and dacarbazine (regular chemotherapy) and achieved a 43% response rate in the phase II trial of 17 patients with stage IV melanoma who failed to respond to all standard treatment. The mean survival rate of these patients increased from the usual 5-9 months. One of the patients experienced complete remission. G3139 acts by turning off Bcl-2 gene expression, which has been implicated in chemotherapy resistance. Side effects of this therapy are minor and include transient fever, flushing and rash. A phase III multicenter, international trial with at least 270 patients is sponsored by Genta Inc. (developer of G3139) and is almost ready to begin.

91st annual meeting of the American Association for Cancer Research

While a number of analgesics are shown to inhibit tumour growth, anti-cancer properties of acetaminophen appear to work earlier during the neoplastic process. According to the recent research at the New York Medical College in Valhalla, acetaminophen can prevent the beginning of colon cancer by blocking the action of food mutagens. Treatment of rats with acetaminophen prior to the administration of 3,2'dimethyl-4-aminobiphenyl (a carcinogen, similar to the one formed during cooking) "produced a marked cytoprotective effect," Dr. Gary Williams, principal investigator of the study, said at the 91st annual meeting of the American Association for Cancer Research. While these results are very exciting, clinical trials with people at risk for colon cancer are necessary to determine whether administration of acetaminophen would reduce this risk in humans.

91st annual meeting of the American Association for Cancer Research

http://cancertrials.nci.nih.gov (Web Page of the National Cancer Institute)

Due to the belief that shark cartilage has anti-angiogenic properties, and despite the lack of comprehensive controlled studies, shark cartilage supplements are being widely used as alternative anti-cancer agents. The perceived anti-cancer properties of shark cartilage have come into question due to the recent discovery that sharks not only get cancer, they get cancer of the cartilage. Dr. John C. Harshbarger, director of the National Cancer Institute Registry of Tumors in Lower Animals at Johns Hopkins University, reported three malignant tumors--renal cell carcinoma, lymphoma, and a new cartilage tumor--in sharks. Light on this issue will be shed by the results of Phase III clinical trial, which is expected to be opened in the next couple of months. A liquid shark cartilage extract AE-941/Neovastat (developed by Aeterna Laboratories Inc., Quebec, Canada) is being administered in combination with conventional cancer therapies to several hundred patients with non-small-cell lung cancer across Canada and USA. Smaller trials evaluating patients with other types of cancers are also being initiated to speed up the potential approval of the drug.

Julia Krestow, BSc, MSc

Brain cancer has long been known as one of the most difficult neoplasms to treat. Since the 1970's there has been little change in its management despite considerable laboratory progress in understanding brain tumour biology. Recently, however, advances in imaging techniques have begun to result in earlier and more accurate diagnosis.¹ Correct diagnosis combined with the standardized World Health Organization (WHO) classification system for tumours constitute the first step in a successful treatment strategy. The primary challenge and rate-determining step in brain cancer treatment is understanding the underlying tumour biology. This will determine tumour resistance to radiation and chemotherapy, tumour location and the degree of vascularity and abnormal vessel formation within a tumour. Together these comprise the main challenges of brain cancer treatment. Current research areas include Magnetic Resonance Imaging (MRI), which increa-ses surgical safety, new chemotherapeutics, such as, small molecule targeting drugs, which selectively kill tumour cells, and the still theoretical field of immunotherapy. Together these offer considerable hope to physicians, patients and their families even for the most malignant cancers generally found in older patients.

Pathology
Brain tumours are classified according to the tumour type and cell of origin. They are also classified as primary and secondary depending on the absence or presence of metastases.

Multiple myeloma (MM) is a tumor of mature, isotope-switched plasma cells. Malignant plasma cells replace normal blood cells in the bone marrow and bloodstream, causing anemia, bleeding disorders, and painful bone deterioration. It has recently been determined that MM is characterized by recurrent chromosome translocations to the immunoglobulins heavy chain gene on chromosome 14q32. The neoplastic event in myeloma may involve cells earlier in B-cell differentiation than the plasma cells. Circulating B-cells bearing surface immunoglobulin that share the idiotype of the M component are present in myeloma patients. It is possible that the malignant clone escapes normal control mechanisms at a pre-plasma cell stage of differentiation and the chronic exposure to a particular antigenic stimulus drives the cell to terminal differentiation.

Approximately 14,400 cases or myeloma were diagnosed in 1996, and 10,400 people died from the disease. There is a correspondingly greater incidence of myeloma with age. The median age at diagnosis is 68 years, and occurence in people younger than 40 years of age is very rare. Males are more commonly affected than females, and there is nearly twice the incidence among African Americans then among Caucasians. There is no cure for MM, nor any effective treatment.

Bone pain is the most common symptom of myeloma and is generally felt in the back and ribs. Bone lesions are caused by the proliferation of tumor cells and osteoclast activation, and result in the destruction of bone. Osteoclast proliferation is a response to osteoclast activating factors secreted by the myeloma cells. The overabundance of nonfunctional antibodies produced by the abnormal cells also inhibits the production of normal protective antibodies, which frequently results in infection. Kidney failure is a common side effect, occurring as a consequence of bone breakdown and increased antibody proteins. Associated complaints include hypercalcemia, nausea, confusion, polyuria and constipation. Many of the complications associated with MM are treatable on a symptom by symptom basis.

Several methods are available for both a preliminary diagnosis and staging of the disease. Peripheral blood examinations can be used as a first diagnostic check for rare plasma cells, normocytic anemia, thrombocytopenia, and leucopenia. Blood chemistry should reveal hypercalcemia, hyperuricemia, increased serum creatinine and renal failure. Bone marrow examination will show focal or diffuse plasma cells. Radiological studies may reveal osteolytic lesions but a complete bone survey is essential for evaluating monoclonal gammopathies. Aspiration and biopsy of bone marrow is used to evaluate cell morphology, and CT and MRI can be used to check for bone destruction.

Several major advances have been made in the treatment of MM. Standard treatment has involved chemotherapy including intermittent pulses of an alkylating agent (melphalan, cyclophosphamide or chlorambucil) and prednisone administered for 4 to 7 days every 4 to 6 weeks. High-dose therapy with hematopoietic support is being investigated in younger patients. Sequential treatment with combination chemotherapy regimens followed by two successive high-dose melphalan treatments, each supported with peripheral blood stem cell transplants, have achieved complete responses in 50% of patients treated within a year of diagnosis. The use of thalidomide has been studied and appears indirectly to inhibit the growth and survival of myeloma cells, bone marrow and/or stromal cells. The mechanism of action of thalidomide is unknown, although it has been postulated to inhibit angiogenesis, cutting off blood supply to the tumors. Novel experimental approaches involve the development of a myeloma vaccine. Vaccination of myeloma patients against a myeloma specfic molecule could be used as an adjunct to conventional therapy to eliminate minimal residual disease and prevent re-emergence of the tumor. One group is investigating the use of bacterial DNA- based vaccines to generate immune responses capable of preventing B cells from expressing a tumor-associated immunoglobulin. Another is using customized vaccines made from each patient's myeloma in association with dendritic cells from a sibling donor to help the immune system recognize the myeloma as abnormal. Both of these methods are in preliminary stages of investigation and results may not be available for some time.

For more detail on the causes, classification, complications and treatments of multiple myeloma please see our web site: www.geriatricsandaging.com.

Sources

Harrison's Principles of Internal Medicine Online. [Editors Braunwald, E, Fauci, AS, Isselbacher, KJ, Kasper, DL, Hauser, SL, DL Longo and Jameson, JL]. McGraw Hill Company. (http://harrisonsonline.com)
Multiple Myeloma Research Foundation (http://www.multiplemyeloma.org)

Nat Jackson

The benefits of physical activity are well known throughout the health care profession. Exercise has found its way into programs for patients with conditions such as heart disease, and it is becoming part of standard care. Studies have now begun to look at whether or not the success of programs which include exercise can also be realized with cancer patients. This form of care seems to have met with success.^1,2,3,4

It now appears that rehabilitation has been defined as the process by which a person is restored to an optimal physiological, psychological, social and vocational status.² In the case of cancer patients, rehabilitation can be a challenge due to the significant side-effects of cancer treatment: fatigue, weakness, impaired nutritional status, difficulty sleeping and nausea. The patient often sees a decrease in normal physical performance, and the resumption of regular activities after therapy is often delayed. New studies have shown that including exercise within the rehabilitation program reduces the above-mentioned side effects, and even shortens the length of stay in the hospital following treatment.¹ In one study, patients who participated in an exercise program during high-dose chemotherapy were discharged, on average, sooner than patients in a control group.

Nariman Malik, BSc

Introduction
Prostate cancer is the most frequently diagnosed cancer in Canadian men,¹ and is the second leading cause of death due to cancer among North American men, just after lung cancer.³ In the early nineties, the number of prostate cancer cases diagnosed increased dramatically. By 1995, the incidence had peaked and has since leveled off in both Canada and the United States. In 1999, it was estimated that there would be approximately 16,600 new cases of prostate cancer in Canada.² This increase can be at least partially attributed to newer methods for detecting the disease earlier, particularly since the introduction of routine serum prostate specific antigen (PSA) testing in the early 1990s.¹

The risk of developing prostate cancer increases with age. Sixty to seventy-five percent of cancers are diagnosed in men who are over 65 years of age.³ Because of Canada's aging population, primary care physicians will see an increasing number of prostate cancer cases in their practices. It is, therefore, of utmost importance that physicians dealing with the elderly have a clear understanding of the various aspects of this disease. This article focuses on these various aspects of prostate cancer: risk factors, screening techniques, diagnosis and treatment modalities.

Related Terms: Cancer, Men’s Health, prostate cancer, PSA-based screening tests

Shabbir M.H. Alibhai, MD, FRCP(C)

It is my pleasure to have been invited to write this editorial on the interface of oncology and aging. As a Geriatrician and a researcher in prostate cancer, this topic is near and dear to my heart. Astute readers will realize that this theme has been employed once before in Geriatrics & Aging. Clinicians will also recognize the tremendous burden that cancer in the elderly imposes--hence our decision to revisit this theme annually. In this issue we have attempted to deal with both commonly discussed tumors not focused on previously (prostate), as well as less commonly discussed malignancies (brain, lymphoma). We hope you find this issue informative.

Recently, there has been a tremendous surge in interest directed at the fields of oncology and aging, coming from a myriad of perspectives. For example, oncology training programs in the U.S. are beginning to have mandatory rotations for trainees in geriatric medicine. Whether Canadians will follow suit remains to be seen. I wish to touch further on three areas--cancer screening in the elderly, trends in treatment, and implicit values.

When we examine recommendations for cancer screening for the elderly (from such internationally respected organizations as the Canadian Task Force on Preventive Health Care), there appear to be no recommendations made (based on current evidence) to screen for any malignancy for anyone over the age of 70 to 75. Most other organizations, no matter how "evangelical", echo the CTFPHC's recommendations' principles. This is most interesting and bears further scrutiny. Why is there such consensus? Is it because cancer is uncommon in the elderly? Hardly. Is disease unlikely to be found at a curable stage? No. In general, and for most tumor types, it occurs more often than in younger patients. Is it because of the proven lack of benefit of screening? Once again, no. In most instances, there is simply a paucity of controlled clinical studies which have included patients in this age group. So what else can the CTFPHC fairly conclude? Could it be that the reasons for the recommendations (or absence thereof) have far more to do with lack of proof of efficacy than proof of lack of efficacy.

…there are countless studies demonstrating that older patients are treated less aggressively than younger patients, even with similar stage and grade of disease.

The lessons we learn from the screening recommendations can be extended to the treatment of cancer in seniors. From surgical therapy for localized prostate and lung cancer to adjuvant therapy for colorectal and breast cancer, to intensive chemotherapy for leukemia and lymphoma, there are countless studies demonstrating that older patients are treated less aggressively than younger patients, even with similar stage and grade of disease. What accounts for this disparity? Closer examination of these studies reveals two main reasons: a perception of decreased life expectancy for an older cancer victim, and an increased risk of toxicity in treating the elderly. Note that lack of efficacy is rarely an issue. Clinicians (and family members) argue that older patients are more likely to die of other causes than of their underlying malignancy. Yet the work of numerous cancer scientists in various fields, including some of my own work in prostate cancer, shows that this is often not the case, especially for higher grades of neoplasm in relatively healthy older people. Furthermore, clinicians generally fare poorly when trying to estimate life expectancy, even for dying patients in a palliative care unit (as one recent study reaffirmed). On the toxicity front, numerous studies in the last few years have supported the notion that body-weight-adjusted chemotherapy is generally well-tolerated by the elderly, often to a degree comparable with younger patients. As concerns the morbidity and mortality of surgery, carefully selected older patients have only slightly higher treatment risks than younger ones--these are nowhere near the figures that some experts have been heard quoting at the bedside. Yet misperceptions flourish.

Something obvious but heretofore unspoken needs to be said. Evidence is accumulating that the attitudes of clinicians who treat cancer are ageist; this is to say they are discriminating unfairly or without due justification against individuals on the basis of age. Implicit in this ageist bias is the value that we place on life. For example, a 50-year-old man with localized high grade prostate cancer will gain 9 years of life with surgery, while a 75-year-old man will only gain 2 years; should we treat the older man? I believe that for too long we have implicitly attached our own values to the years of life gained from intervention. If this was done systematically and openly, supported by the society at large, that would be one thing. Done haphazardly and secretly, it is far from ideal. Without question, our patients, young and old, should carefully assess the quantity and quality of life, with or without treatment, before making any decision. Unfortunately, when it comes to the elderly, it has become amply clear that they are not even being given the chance to choose for themselves.

Dr. Tabo Sikaneta, MD
Clinical and Research Fellow
Massachusetts General Hospital
Harvard Medical School

Chronic myeloid leukemia (CML) and chronic lymphocytic leukemia (CLL) are malignant hematologic disorders that predominantly affect the middle-aged and elderly. Although they share certain features in their clinical presentations, these two neoplasms differ significantly with regard to epidemiology, pathogenesis, prognosis, and management issues. This article will compare and contrast CML with CLL in order to highlight these important clinical differences. Particular attention will be given to the treatment issues faced by elderly patients with these chronic leukemias, and to the role that primary care physicians may play in the management of these diseases.

Definition and Epidemiology
CML is the clonal proliferation of hematopoietic stem cells. CLL is the clonal proliferation of small, long-lived, mature B lymphocytes. CML is less common, with an annual incidence of 1-2 per 100,000 members of the general US population. It has an equal distribution among both sexes.¹ Both CML and CLL affect whites more than blacks, are not familial, and are not related to a history of known carcinogenic agent exposure.² Although the median age of onset of CML is 53, a sizeable minority (10-30%) contract CML after age 60.

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concerningcancer.com

Advanced Melanoma Successfully Treated with Antisense Therapy

The Wonders of Acetaminophen: It Also Protects From Colon Cancer

Shark Cartilage: Just Another Unicorn’s Horn?

Treating Brain Cancer: New Therapies Offer Hope for the New Millenium

Multiple Myeloma, Killer Without a Cure

Physical Activity Found Beneficial in Oncology Rehabilitation

New PSA-Based Screening Tests for Prostate Cancer

Oncology and Aging--Bitter Truths and Misguided Paternalism

Chronic Leukemias in the Elderly--Comparing CML and CLL