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ASCP is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.
This home study web activity has been assigned 3.5 credit hours. ACPE UPN: 0203-0000-10-041-H-01-P Release Date: 3/15/2010 Expiration Date: 3/15/2013
To receive continuing education credit for this course, participants must complete an on-line evaluation form and pass the online assessment with a score of 70% or better. If you do not receive a minimum score of 70% or better on the assessment, you are permitted 4 retakes. After passing the assessment, you can print and track your continuing education statements of credit online.
Geriatric Pharmacy Review courses have not yet been approved for Florida consultant pharmacy continuing education.
Content Experts
Trinh Pham, PharmD, BCOP Assistant Clinical Professor University of Connecticut School of Pharmacy Yale New Haven Hospital
By the end of this Review Concept you should be able to: Describe the incidence and mortality trends associated with oncological disorders among the elderly Describe the process of malignant transformation and the development of a clinically significant tumor Cite some of the current theories regarding the relationship between age and the incidence of cancer Describe primary strategies for the prevention and treatment of cancer Explain the importance of early cancer screening and reasons why early detection is difficult Understand the importance of a comprehensive geriatric assessment and its role in determining the appropriate therapy for the elderly cancer patient List the patient and disease related factors that influence the choice of cancer treatment Describe the complications that can occur as a result of cancer treatment and how they are managed
Cancer is the second leading cause of death in the United States and it is a major problem for the elderly. The most common cancers include breast, lung, colon, and prostate. The incidence of cancer increases with age and it is estimated that by the year 2030 approximately 20% of the United States population will be 65 years of age or older, compared to 12.4% at the present time. Since over 60% of all newly diagnosed cancers and 71% of all cancer deaths occur in persons over the age of 65, it may be expected that the burden of cancer care will rise dramatically in the United States in the future.This shift in the population demographics is due to the aging of the baby boomers and has created an increased interest in developing programs and fostering research focusing on the optimal care of geriatric cancer patients.This module will focus on the management of cancer in the geriatric patient population and the following specific areas will be addressed:the biology of cancer in the older person; the goals of cancer prevention in the elderly; the determination of the fitness of the elderly patient using the comprehensive geriatric assessment; the pharmacologic, pharmacodynamic and pharmacokinetic changes involved with the process of aging, their impact on therapy selection and consequences on toxicity outcomes; the evidence based guidelines for the treatment of cancer; and, lastly, the evidence based guidelines for the management of toxicities related to the treatment of cancer.
Malignant transformation or carcinogenesis involves a number of different genetic alterations that occur sequentially in a cell. These alterations include deletion of tumor suppressor genes, the mutation of proto-oncogenes, and other chromosomal aberrations. These genetic changes may be caused by exposure to carcinogens, viruses or occur as a result of hereditary predisposition. The result is the generation of cells that lack the specific appearance and function of the normal cells. Under normal conditions, hormones and growth factors tightly control the proliferation of cells; however, these control mechanisms have failed in the process of carcinogenesis and the result is an uncontrolled proliferation of malignant cells that eventually may invade and metastasize to other tissues in the body.
As a person ages, the potential for malignant transformation of cells increases.Why is there this increased risk with age? Several theories have been proposed to explain the increased susceptibility of cells to neoplastic alteration in older adults. First, older persons have less resistance and longer exposure to carcinogens. They also have a decline in their immune function, changes in defense mechanisms against tumors, and furthermore, they have defects in tumor suppressor genes and a decreased ability to repair DNA.
Copyright 2011 American Society of Consultant Pharmacists
For most cancers, there is no consistent difference in clinical presentation for different age groups. While the five-year survival rate for many cancers is lower in the elderly, there are some cancers that behave less aggressively in older adults and sorting out the biologic factors that differentially affect neoplastic behavior in elderly patients is complex.
Colorectal Cancer
Ter:ary3
Lung Cancer
Secondary
Secondary
Ter:ary
1-Prevent de novo malignancies in otherwise healthy person 2- Prevent the progression of pre-malignant lesions to cancers 3- Preventing second primary tumor in patients cured of initial cancer
An encouraging area of research in oncology is in the field of cancer prevention. This is an enticing concept because the proactive approach of cancer prevention may eliminate or decrease the chance of being diagnosed with cancer, preserve life, and avert the complications associated with a malignancy or its treatment. However, when cancer prevention is being considered in the elderly, it is essential to consider that due to the limited life expectancy of this population, the benefit of survival gain may be reduced. Thus, the value of chemoprevention should be assessed in terms of its potential in averting cancer-related morbidity and preserving quality of life in addition to the outcome of possible gain in survival time. Cancer prevention may be either primary or secondary. Primary prevention involves the elimination of exposure to carcinogens and environmental factors that are associated with the growth of some cancers.Chemoprevention, defined as the administration of natural, synthetic, or biologic chemical agents to suppress, reverse, or prevent the development of cancer, is also considered to be primary prevention.
Cancer screening guidelines in the elderly patient is uncertain. The recommendations for this population should not be based exclusively on age-specific guidelines but rather accompanying factors such as life expectancy, the risk of cancer related deaths, the potential for harm due to psychological stress, the possibility of false positives, and the possibility of treating clinically insignificant cancers should be taken into consideration.
Signs/Symptoms Increased Skin Pigment Age Spots Rectal Bleeding Cons:pa:on Dyspnea Decreased Urinary Stream Breast Change Fa:gue
Possible Malignancy Melanoma Squamous Cell Carcinoma Colorectal Rectal Lung Prostate Breast Metasta:c or Hematologic Cancer Metasta:c Cancer, Mul:ple Myeloma
Confused with
Hemorrhoids, Aging
Aging, Out of Shape Dribbling, BPH Normal Atrophy Aging, Out of Shape
Bone Pain
Arthri:s, Aging
Assessment of Aging
Category
of
Aging
Young-Old
Old-Old
Oldest-
Old
Age
Range
70-75
years
76-84
years
>
85
years
Beginning
of
frailty
ClassicaAon
Beginning
of
senescence
Comprehensive Geriatric Assessment (CGA) Domain Health Instrument Number of comorbid condi:ons Charlsons Comorbidity Scale Chronic Illness Ra:ng Scale-Geriatric Performance Status Instrumental Ac:vi:es of Daily Living (IADL)- (shopping, use of transporta:on, cooking, cleaning, managing money, taking medica:ons) Ac:vi:es of Daily of Living (ADL)- (bathing, grooming, toile:ng, dressing, feeding, appropriate behavior)
(CIRS-G) FuncAon
Assessment of Aging
Comprehensive Geriatric Assessment (CGA) Domain CogniAon Instrument Folstein Mini Mental Status (MMS) Demen:a Ra:ng Scale (DRS) Geriatric Depression Scale (GDS) Living condi:ons, marital adjustment, caregiver adequacy, caregiver stress, income, transporta:on Mini Nutri:onal Assessment (MNA) Drug list and interac:on
Defining the Frail Elderly Age > 85 Dependence in 1 or more activities of daily living (ADLs) 3 or more comorbid conditions 1 or more geriatric syndromes
Assessment of Aging
Originating from Medicare and Social Security regulations, the arbitrary definition of geriatric or elderly is a person who is 65 years of age or older. This population, however, is heterogeneous and the definition does not reflect the underlying health status of the individuals in this group. Although aging is associated with a progressive decline in a persons functional reserve, this is an individualized process and different people develop disease, functional restrictions and physiologic limitations at varying rates that are not reflective of chronologic age. It is significant, however, to note that starting at the age of 70 years, the incidence of age related changes increases steeply and starting at the age of 85 years the functional reserve is almost exhausted and an individual may be categorized as frail elderly. Given this diversity of functional status in the elderly population, the process of assessing the fitness of these individuals is challenging. The comprehensive geriatric assessment is a multidisciplinary tool, which assesses the domains of health, functional status, nutrition, cognition, socio-economic aspects, and emotional aspects that are likely to change with aging. This multidimensional, interdisciplinary patient evaluation instrument is effective in identifying unsuspected comorbid conditions, physical or emotional dysfunction, and incompetence in daily functional activities. These factors have been shown to be independent predictors of survival and are vital in determining the ability of the patient to undergo and withstand surgery, cytotoxic therapy or other types of treatment. The National Comprehensive Cancer Network (NCCN) has developed guidelines for the treatment of older patients with cancer to ensure that therapy is adequate, toxicities are avoided, and quality of life is maintained. Performing a comprehensive geriatric assessment is one of their recommendations for the initial evaluation of elderly patients diagnosed with cancer.
Aggressive surgery, radiation therapy, and standard chemotherapy are viable treatment options for the elderly patient diagnosed with cancer.Elective cancer surgery and standard doses of radiation therapy is tolerated well by patients even in their 80s.Therefore, the arbitrary implementation of less aggressive therapy for cancer patients based upon chronologic age is not acceptable as there are no data to support this practice.
Pharmacokinetics in the Elderly Patient & Considerations for Chemotherapy Drug Administration
Absorption Decreased gastrointestinal motility Decreased splanchnic blood flow Decreased secretion of digestive enzymes Mucosal atrophy Distribution Increased body fat Decreased intracellular water content Decreased plasma albumin Decreased red blood cell concentration Metabolsim Decreased liver size and liver blood flow Decreased Phase I metabolism CYP450 1A2:20 30% decrease in clearance Excretion Decreased renal mass Decline in renal function and glomerular filtration rate (GFR)
Pharmacokinetics in the Elderly Patient & Considerations for Chemotherapy Drug Administration
Dose Modification with Renal Impairment Dose Modification with Hepatic Impairment, Elevated Bilirubin Bleomycin Anthracyclines Daunorubicin Doxorubicin Epirubicin Idarubicin Busulfan Etoposide Carboplatin Fluorouracil Capecitabine Imatinib Carmustine Taxanes Paclitaxel Docetaxel Cisplatin Vinca Alkaloids Vincristine Vinorelbine Vinblastine Cytarabine
Copyright 2011 American Society of Consultant Pharmacists
Pharmacokinetics in the Elderly Patient & Considerations for Chemotherapy Drug Administration
It is reasonable to anticipate that an elderly person may have reduced functional reserve of many organ systems and that the pharmacologic, pharmacodynamic and pharmacokinetic aspects of drug therapy will be altered. The absorption of oral chemotherapy agents may be reduced due to mucosal atrophy, decreased splanchnic blood flow or secretion of digestive enzymes. As a person ages, their body fat content doubles and intracellular water decreases which results in decreased volume of distribution of polar drugs and increase in volume of distribution of lipid soluble drugs. Furthermore, the reduction in serum albumin and red blood cell concentration associated with aging may increase the toxicities of chemotherapy agents that have high binding affinity with these compounds due to the increase in free drug concentrations. Chemotherapy drugs that are metabolized by the cytochrome P450 system may be affected since it has been demonstrated that there is a decrease in clearance of CYP1A2 by 20-25% in healthy elderly patients as compared to younger patients. And lastly, the decline in renal function as manifested by the decrease in glomerular filtration rate may result in elevation in serum concentrations and toxicity of drugs that are mainly renally eliminated. In spite of all of these anticipated changes in organ function in the elderly, the key message however, is that chemotherapy should be tailored for the individual patient and the doses of the drug should be adjusted based upon the patients calculated glomerular filtration rate and liver function status as assessed by liver enzymes and bilirubin levels. There is no data to corroborate an empiric dose decrease based on chronological age alone.
Chlorambucil
In the last 20 years the availability of oral chemotherapy agents for the treatment of various malignancies has increased. Factors such as patient preference, improved quality of life, and cost of therapy have been influential in the development of these agents. On the other hand, the issue of compliance can be a major obstacle in the implementation of an oral chemotherapy regimen. Some factors associated with higher rates of noncompliance include lower socioeconomic status, treatment in a community based setting, female gender, poor recall of the medication regimen, and the complexity of the medication regimen. The implication is that the effectiveness of the medication will be diminished and the chance of disease free survival is affected if the patient is not taking their medication as directed.
Another facet to consider in the use of oral chemotherapy is the issue of polypharmacy and drug interactions.On average, the older patient takes at least four medications and self-medication with alternative herbal therapies is increasing. The consequence is an increase in the probability of drug interactions and toxicities. The dilemmas that may limit the use of oral chemotherapy agents can be minimized by prescribing simple dosage regimens, suggesting the use of devices that helps with compliance, and educating patients on the importance of adhering to the dosing schedule and the necessity of consulting with a pharmacist or other health care providers prior to self initiation of alternative therapies. On the whole, the expanding role of oral chemotherapy in the treatment of malignancies is a positive step forward in providing cancer patients with more options, convenience, and control in the management of their disease.
Consequences of Neutropenia Increased risk of infection Febrile neutropenia Hospital admission Antibiotic administration
Consequences of Older Age and Chemotherapy Administration Increased neutropenic complications Increased risk of febrile neutropenia (FN) Increased risk of death from FN Reduced dose intensity of chemotherapy Increased risk of 1st cycle hematologic toxicity
Role of Colony Stimulating Factors in Elderly Patients: Should be administered in patients older than 70 years of age receiving moderately toxic chemotherapy: i.e., CHOP (Cyclophosphamide, doxorubicin, vincristine, prednisone) Or regimens with toxicity level of CHOP Consider adding colony stimulating factor early in the course of treatment i.e. 1st or2nd cycle of chemotherapy
Anemia Toxicity Scale Grade Severity NCI1 Scale (Hemoglobin in g/dl) 10-normal* WHO2 scale (Hemoglobin in g/dl) 9.5 10
Mild
2 3 4
National Cancer Institute Definition of Anemia Male: Normal Hemoglobin =14 - 18 g/dl Female: Normal Hemoglobin =12-16 g/dl
World Health Organization Definition of Anemia Male: Hemoglobin < 13 g/dl Female: Hemoglobin < 12 g/dl
Risk Factors for Developing Symptomatic Anemia Transfusion in past 6 months History of prior myelosuppressive therapy History of radiation therapy to > 20% of skeleton Myelosuppression potential of current therapy Age Hemoglobin level
Anemia is one of the most common symptoms experienced by patients diagnosed with cancer.The causes may be the underlying cancer disease, nutritional deficiencies, anemia of chronic disease, the toxic effect of therapy such as chemotherapy or radiation, or a combination of these factors. According to the World Health Organization, the definition of anemia is a hemoglobin level less than 13 g/dl in males and less than 12 g/dl in female.There is a minor discrepancy in the definition for mild and moderate anemia between the National Cancer Institute and the World Health Organization; however, they are identical in their classification of more severe anemia.
Indications for Erythropoietin Asymptomatic with risk factors of developing anemia Symptomatic - Consider when Hgb = 10 11 g/dl Strongly consider when Hgb < 10 g/dl Package Insert Recommendation Epoetin alfa 150 units/kg or 10,000 units; administered SC 3x a week dose to 300 units/kg or 20,000 units; administered SC 3x a week Darbepoetin 2.25 mcg/kg/week SC up to 4.5 mcg/kg/week SC
Common Clinically Used Regimens Epoetin alfa 40,000 units weekly SC dose to 60,000 units weekly SC Darbepoetin 3 mcg/kg every 2 weeks SC to 5 mcg/kg every 2 weeks SC Darbepoetin 200 mcg every 2 weeks SC up to 300 mcg fixed dose every 2 weeks SC Reduce dose by 25% if Hgb by > 1 g/dl in 2 week period Hold Therapy if Hgb > 12 g/dl, reinitiate 75% of dose when Hgb < 12 g/dl
* All patients should have iron panel studies with serum iron, total iron binding capacity, and serum ferritin and add iron supplementation if ferritin is < 100 and transferrin saturation is < 20%
High (>90%)
There are many pharmacologic options for the treatment of chemotherapy induced nausea and vomiting and they include the serotonin antagonists, corticosteroids, phenothiazines, anticholinergics, and the newly approved neurokinin antagonists. The administration of the serotonin antagonist in conjuntion with a corticosteroid has been proven to be effective in the management of acute-onset nausea and vomiting and should be considered as first line therapy for highly to moderately emetogenic chemotherapy regimens. The NK-1 antagonist, aprepitant, should be added for multi-day chemotherapy regimens that are highly emetogenic and is associated with significant risk for delayed nausea and vomiting.
References
For additional information, see: Balducci L. Anemia, Cancer, Aging. Cancer Control 2003 Nov/Dec; 10(6); 478-484. Balducci L. Evidence-based management of cancer in the elderly. Cancer Control 2000 Jul/Aug; 7(4); 368-374. Balducci L, Beghe C. Prevention of cancer in the older person. Clin Geriatr Med 2002 Aug; 18(3); 505-528. Balducci L, Beghe C. Cancer and age in the USA. Crit Rev Oncol Hematol 2001;37;137-145. Balducci L, Beghe C. The application of the principles of geriatrics to the management of the older person with cancer. Crit Rev Oncol Hematol 2000;35;147-154. Balducci L, Extermann M. Cancer and aging. An evolving panorama. Hematol Oncol Clin North Am 2000 Feb;14(1);1-16. Balducci L, Hardy CL, Lyman GH. Hemopoietic reserce in the older cancer patient: clinical and economic considerations. Cancer Control 2000 Nov/Dec; 7(6); 539-546. Balducci L, Lyman G, Ozer H. Patients aged > 70 are at high risk for neutropenic infection and should receive hemopoietic growth factors when treated with moderately toxic chemotherapy. J Clin Oncol 2000; 19; 1583-1585. Balmer C., Valley A. W.(1996).Basic Principles of cancer treatment and cancer chemotherapy. In: Dipiro JT, Talbert RL, Yee GC, et al. (Eds). Pharmacotherapy: A Pathophysiologic Approach. Samford: Appleton and Lange, 2403-2466. Carbone PP. Advances in the systemic treatment of cancers in the elderly. Crit Rev Oncol Hematol 2000;35;201-218.
References
Cohen, H. J.(1994).Oncology and aging:Generaly principles of cancer in the elderly.In Hazzard, W. R., Bierman, E.L., Blass, J. P., Ettinger, W. H. & Halter, J. B. (Eds.). Geriatric Medicine and Gerontology, 3rd ed.New York:McGraw-Hill: 77-90. Ettinger, D. S. (1995).Preventing chemotherapy-induced nausea and vomiting: An update and a review of emesis. Semin Oncol; 22(4) Suppl 10:6-18. Groopman JE, Itri L. Chemotherapy-Induced Anemia in Adults: Incidence and Treatment. J Natl Cancer Inst 1999 Oct; 9(19); 1616-1634. Grunberg,S. M., HeskethP. J. (1993). Control of chemotherapy-induced emesis. N Engl J Med; 329(24):1790-97. Jacox, A. K., Carr, D. B, Payne, R, et al. (1994). Management of cancer pain. Clinical practice guideline no. 9. Rockville, MD: Agency for Health Care Policy and Research (AHCPR publication no. 94-0592).
Kennedy BJ. Aging and cancer. Oncology (Huntingt)2000 December; 14(12);1731-1740. Levy, M. H. (1996). Pharmacologic treatment of cancer pain. N Engl J Med; 335(15):1124-32. Lichtman, SM. Chemotherapy in the elderly. Semin Oncol 2004 April; 31(2);160-174. Lichtman, SM. Guidelines for the treatment of elderly cancer patients. Cancer Control 2003 Nov/Dec; 10(6); 445-452. Lichtman, S. M. (1995). Physiological aspects of aging Implications for the treatment of cancer. Drugs-Aging;7(3):212-21.
References
National Cancer Institute http://www.nci.nih.gov/ National Comprehensive Cancer Network. Practice Guidelines in Oncology. Version.1.2004. Antiemesis National Comprehensive Cancer Network. Practice Guidelines in Oncology. Version.2.2004. Cancer and Treatment Related Anemia. Pharmaceutical Information Network: Cancer Information Center http://pharminfo.com/disease/cancer_db.html Pizzo, P. A. (1993). Management of fever in patients with cancer and treatment-induced neutropenia. N Engl J Med; 328 (18):1323-1332. Portenoy, R. K. (1993). Cancer pain management. Semin Oncol;20(2) Suppl 1:19-35. Repetto L, Biganzoli L, Koehne CH, Luebe AS, Soubeyran P, Tjan-Heijnen VCG, Aapro MS. EORTC Cancer in the elderly tsk force guidelines for the use of colony-stimulating factors in elderly patients with cancer. Eur J Cancer 2003; 39; 2264-2272. Repetto L, Balducci L. A case for geriatric oncology. Lancet Oncol May 2002; 3; 289-297. Repetto Lazzaro, Comandini D. Cancer in the elderly: assessing patients for fitness. Crit Rev Oncol Hematol 2000;35;155-160. Rosti G, Kopf B, Cariello A, Monti M, Dazzi C, Papiani G, et al. Prevention and therapy of neutropenia in elderly patients. Crit Rev Oncol Hematol 2003; 46; 247-253.
References
Schwartz R. N. (1995). Cancer in the Elderly. In: Delafuente J. C., Stewart,R. B., (Eds.) Therapeutics in the elderly. Cincinnati: Harvey Whitney Books, 500-12. Tsao AS, Kim ES, Hong WK. Chemoprevention ofCancer. CA Cancer J Clin 2004 May/June; 54; 150-180. University of Pennsylvania Cancer Center: OncoLink http://cancer.med.upenn.edu/ Yancik R, Ries L Aging and cancer in America. Demographic and epidemiologic perspectives. Hematol Oncol Clin North Am 2000 Feb;14(1);17-23 Yancik R, Ries L.Cancer in older persons: An international issue in an aging world. Semin Oncol 2004 Apr;31(2):128-136 Zagonel V, Fratino L, Sacco C, et al. (1996). Reducing chemotherapy-associated toxicity in elderly cancer patients. Cancer Treat Rev; 22:223-244. Zoorob R, Anderson R, Cefalu C, Sidani M. Cancer screening guidelines. Am Fam Physicians 2001; 63: 1101-1112. Zulian GB. Health care delivery in the older person with cancer. Crit Rev Oncol Hematol 2000;35;227-232.
Cite the epidemiologic trends associated with lung, breast and brain cancers. Differentiate the signs and symptoms of presentation and diagnosis of lung, breast and brain tumors. Analyze the various treatment regimens and related effects for lung, breast and brain cancers. List common sites for metastases for lung, breast and brain cancers.
Lung Cancer
Incidence Estimated 219,440 new cases in 2009 Male: 116,090 cases Female: 103,350 cases Mortality Estimated 159,390 deaths in 2009 Male: 88,900 deaths Female: 70,490 deaths Overall 5 year survival rate is 15% 88% mortality rate More than 2/3 of patients are over 65 years of age Epidemiology in Elderly Patients Median age at diagnosis is 69 years More than 50% are over 65 years of age More 30% are over 70 years of age Lung cancer is the most common cause of cancer-related death in both men and women in the United States. It accounts for 15% of all cancer diagnosis and 29% of all cancer related deaths. The risk of developing lung cancer rises with age. During the last decade, the incidence and mortality from lung cancer has decreased among individuals who are 50 years of age or younger; on the other hand, the incidence has increased among those 70 years of age and older. In considering gender, the incidence rate of lung cancer declined significantly in men and the death rate declined at 2% per year from 1994 to 2004. In women, there was a sharp rise in lung cancer incidence in the 1960s and since 1987, more women have died from lung cancer than breast cancer. After increasing for many decades in women, the lung cancer death rates are finally approaching a plateau
Lung cancer is divided into 2 major histologic types: non-small cell lung cancer and small cell lung cancer. Non-small cell lung cancer is the more common subtype and accounts for more than 85% of all lung cancer cases. Small cell lung cancer accounts for only 15% of all lung cancer cases. Non- small cell lung cancer is often diagnosed in the advanced stage of the disease and is generally considered to be chemotherapy resistant. Small cell lung cancer is rarely cured and it is characterized by a rapid doubling time, high growth fraction, and early development of metastasis. Non-small cell lung cancer is further classified as adenocarcinoma, squamous cell carcinoma and large cell carcinoma. Adenocarcinoma is the most common subtype and is most frequently observed in patients who never smoked, women, and is rising in incidence in younger adults. Adenocarcinoma may also metastasize rapidly to other sites such as liver, bones, brain, and adrenal glands. Squamous cell carcinoma is the second most common subtype of non-small cell lung cancer and tends to be more indolent.
Tobacco 20 fold increase in lung cancer risk cause of 90% of lung cancers in men cause of 75-85% of lung cancers in women Exposed non-smokers (second-hand smoke) 25-35% increased risk compared to nonsmokers Genetic predisposition Family history Germ-line mutation in: DNA repair genes Epidermal growth factor receptor gene p53 tumor suppressor gene Occupational and chemical exposure Radon, ionizing radiation Asbestos Arsenic Chromium Nickel
Cigarette smoking is the most important risk factor for lung cancer. Smoking causes all types of lung cancer but it is most strongly linked with small cell lung cancer and squamous cell lung cancer. There is a dose-response relationship in the development of lung cancer where the risk increases with increased duration of smoking and the number of cigarettes smoked per day. The risk of developing lung cancer decreases after smoking cessation and quitting smoking can benefit at any age no matter how long a person has smoked. The decrease in risk, however, will not be equal to that of a non-smoker. Reports of familial clustering of lung cancer suggest that there is a hereditary basis to the development of lung cancer. Lung cancer susceptibility and risks are increased in germ line mutations p53 tumor suppressor genes, epidermal growth factor receptor genes or DNA repair genes. Other less common causes of lung cancer include exposure to radon gas, asbestos, and carcinogenic chemicals such as organic arsenic compounds, nickel, and chromium.
A new or changing cough that is sometimes associated with blood is the most common presenting symptom of lung cancer. Frequently, patients may also manifest dyspnea, hoarseness, anorexia, weight loss and fatigue. Patients with metastatic disease to the brain can present with neurologic symptoms such as severe headaches and double vision. Other extrapulmonary symptoms include bone pain or pathologic fractures secondary to bone metastasis or liver dysfunction due to spread of the cancer to the liver. Compression of the superior vena cava by the lung cancer may cause patients to develop shortness of breath and swelling of the face and arms because blood is not able to return to the heart. Patients with small cell lung cancer may present with a paraneoplastic syndrome, which are a collection of symptoms that result from the production of biologically active substances by the tumor. These signs and symptoms occur remotely from the primary tumor site or the metastatic site and may be endocrine, neuromuscular or musculoskeletal in nature. Eaton Lambert myasthenic syndrome presenting with proximal leg weakness is an example of a neurologic manifestation. SIADH due to the production of vasopressin or Cushings syndrome due to the production of adrenocorticotropic hormone by the cancer cells is a another common manifestation of the paraneoplastic syndrome.
Copyright 2011 American Society of Consultant Pharmacists
Factors that predict good prognosis include early stage at diagnosis, good performance status, weight loss of less than 5%, and female gender. Unfortunately, only about 30% of non-small cell lung cancer patients are diagnosed with stage I or II of the disease, the remaining 70% are diagnosed with advanced stage III or IV. For small cell lung cancer, about one-third of patients present with limited disease and two thirds present with extensive disease. As can be seen from the table, 5-year survival rate is highest for patients diagnosed with stage I or II non small cell lung cancer. Survival is poorest in patients diagnosed with extensive stage small cell lung cancer where the 2-year survival rate is less than 5%.
Radiotherapy Unresectable cancers (stage I through IIIB) Radiation alone or in combination with chemotherapy Adjuvant radiation therapy with chemotherapy after surgery Stage III Surgical resection is the cornerstone of therapy for patients with stage I through IIIA non-small cell lung cancer. For stage I and II disease, it is the best option for cure if the cancer can be completely resected and the patient is able to tolerate the surgical procedure. Radiation with curative intent is a viable alternative for patients who are not able to tolerate surgery because of other comorbid conditions. It also indicated for non-resectable stage IIIB non-small cell lung cancer. For these situations, radiation is usually administered in combination with chemotherapy to optimize outcome. Radiation in combination with chemotherapy is also indicated as adjuvant therapy after surgical resection in patients with stage IIIA disease.
Elderly cancer patients often present with multiple comorbidities and physiological limitations such as decreased organ function that makes it challenging to select optimal treatment options for them. Furthermore, in lung cancer, if the patient underwent surgical resection, they may also be at higher risk for experiencing chemotherapy induced toxicity. There are few prospective studies evaluating the tolerability of chemotherapy in elderly patients with lung cancer. Available data are usually from retrospective analysis and is not ideal for basing treatment decisions. More clinical trials that are specific for the elderly patient population are needed in order to better define optimal therapy for elderly patients. For many stages of lung cancer, cisplatin based chemotherapy with or without radiation is the standard of care. Some elderly patients may be able to tolerate the toxicity of these regimens and derive survival benefit; therefore, dose reduction of chemotherapy or withholding chemotherapy should not be a priori planned strategy for elderly patients diagnosed with lung cancer. There are phase III trials that support the use of single agent chemotherapy in place of best supportive care for patients with metastatic disease who are not able to tolerate combination chemotherapy. Patients with good performance status, adequate organ function and minimal comorbid conditions should be carefully selected for chemotherapy or combination therapy with radiation. If the data is available, the decision should be supported by data from clinical trials that are specifically designed to evaluate the effect of therapy in elderly patients.
Recommendations Fluid restriction, saline for symptomatic patients, demeclocycline, treat the cancer Consider ketoconazole Cough suppressants: opioid and nonopioid (e.g. dextromethorphan). Consider steroid therapy if coughing is secondary to radiation pneumonitis Short acting opioids, oxygen, relieve anxiety (benzodiazepine), relaxation techniques, cool air or fan Hydration, furosemide, bisphosphonate Radiation to shrink tumor and relieve symptoms of SVC obstruction
Cough
Dyspnea
Recommendations Wound healing complications Do not administer bevacizumab within 28 days of any major surgery Nephrotic syndrome- monitor proteinuria by dipstick urinalysis. If urine dipstick is 2+ or greater, obtain 24 hour urine collection. Adminster bevacizumab only if proteinuria is less than 2gm/24 hours Hypertension- monitor blood pressure every 2 to 3 weeks during treatment with bevacizumab. Initiate appropriate anti hypertensive medication if hypertension develops Hemorrhage- do not administer to patients with serious hemorrhage or recent hemoptysis. If bleeding occurs discontinue bevacizumab GI perforation discontinue bevacizumab if this occurs
Surveillance After Lung Cancer Treatment After recovery from primary therapy Non-Small Cell Lung Cancer History and Physical Exam CT scan Year One Every 4 to 6 months Year Two Every 3 to 4 months Year Three Year Four Year Five Year 6 and beyond Annually Every 4 to 6 months Small Cell Lung Cancer History and Physical Exam Chest imaging Blood work as necessary Every 2-3 months
Annually
Breast Cancer
Deaths
60 years of age and older 70% of breast cancer patients 70 years of age and older 46% of breast cancer patients Breast cancer incidence is 6-fold higher in elderly women Breast cancer mortality rate is 8-fold higher in elderly women
Copyright 2011 American Society of Consultant Pharmacists
Breast Cancer
Breast cancer is the most commonly diagnosed cancer in American women and accounts for thirty two percent of all malignancies. It is the second leading cause of cancer death among women, trailing only after lung cancer. From 2001 to 2004, the incidence of breast cancer started to decline by 3.5% per year, after continuously increasing in incidence for more than 2 decades. This is attributed to the reduced use of hormone replacement therapy after publication of results that linked hormone replacement therapy use to increased risk of heart disease and breast cancer from the Womens Health Initiative study in 2002. The National Health Interview survey showed that the rate of mammography screening in women 40 years of age and older dropped from 70% in 2000 to 66% in 2005 and this maybe another contributing factor to the decline of breast cancer incidence rates. Breast cancer mortality has steadily decreased since 1990, with larger decreases in women younger than 50 years of age compared to women who are 50 years of age or older. The reason may be due to breast cancer screening, which detects the disease earlier, and the availability of improved treatment options. Breast cancer is a disease of aging and more than 50% of breast cancer cases occur in women 60 years and older. As the elderly population in the United States is increasing due to the aging of the baby boomers, the number of older patients diagnosed with cancer will also increase accordingly. By the year 2030 an estimated 70.2 million people will be over the age of 65 and the number of women diagnosed with breast cancer will increase by 72%.This escalating number of elderly women who will be diagnosed with breast cancer stresses the need for more research focusing in this patient population for the best evidence to prevent and treat the disease.
Modified Gail Model of Breast Cancer Risk Assessment: A model to determine the relative risk of developing breast cancer Analyzes the combination of the following factors: History of ductal or lobular carcinoma in situ Age (> 35 years) First degree relatives with breast cancer Prior breast biopsies and presence of atypical ductal hyperplasia Age at menarche Age at first live birth Ethnicity Many risk factors are associated with the development of breast cancer; however, it should be noted that 60% of women with breast cancer have no identifiable major risk factors, emphasizing that the actual cause of breast cancer is largely unknown. Aside from being female, age is the most significant risk factor for the development of breast cancer. A positive family history of breast cancer, a previous diagnosis of breast cancer or benign breast disease such as hyperplasia, or high dose radiation to the chest are additional risk factors. Mutations of the breast cancer 1 or 2 gene, otherwise known as BRCA1 or BRCA2 gene, predisposes the woman to an 80% lifetime risk of developing breast cancer. BRCA1 or BRCA2 gene mutation accounts for 5 to 10% of all breast cancer cases and only 1% of the general population has a mutation in either of these genes.
Intervention
Benefits
Indications
~ 50% risk of developing breast cancer Tamoxifen * Limited data for women with BRCA 1/2 mutation
Premenopausal Thromboembolism Postmenopausal Stroke * 35 years or older with Gail model 5 year breast cancer risk greater than 1.7 Cataract * Hot Flashes Endometrial cancer Postmenopausal Thromboembolism Hot flashes All the side effects are less compared to tamoxifen
Raloxifene
Equivalent to tamoxifen
* 35 years or older with Gail model 5 year breast cancer risk greater than 1.7
Benefits 50% risk of breast cancer 85% risk ovarian cancer * Protects women with BRCA 1 or 2 mutation
* Cognitive changes
Effective means for preventing breast cancer are limited. The antiestrogen tamoxifen is approved by the FDA for reduction of breast cancer in high-risk women. This is based upon results from the NSABP Breast Cancer Prevention Trial that showed a 49% decrease in the short-term risk of developing breast cancer when tamoxifen is initiated in a woman with high risk of developing breast cancer based upon the Gail Model of breast cancer risk assessment. .Raloxifene was originally evaluated to determine fracture risks in postmenopausal women with osteoporosis. Secondary analysis in this study showed that breast cancer risk was reduced in patients receiving raloxifene compared to patients receiving placebo. Thus, this lead to the STAR trial, which is a Study of Tamoxifen and Raloxifene in postmenopausal women at risk of developing breast cancer. Raloxifene was found to be equivalent to tamoxifen in decreasing the risk of developing breast cancer and is FDA approved for postmenopausal women.
Breast Cancer Early Detection Guidelines from the American Cancer Society
Screening Recommendations Breast Self Exam (BSE) Clinical Breast Exam (CBE) Mammogram3 Monthly starting at 20 years Every 3 years in 20s and 30s Annually starting at 40 years Annually starting at age 40 years
Women at increased risk due to family history, past breast cancer history, previous radiation therapy to chest wall, or other risk factors. should consult their physician regarding earlier mammogram screening, more frequent exams or additional tests such as ultrasound or MRI. http://www.komen.org/bse website has video instructions on performing BSE Mammography Screening Recommendations for Elderly American Cancer Society and American College of Preventive Medicine No recommendation of when to stop screening based upon age. Should take into consideration patients comorbid conditions American Geriatric Society Mammography every 3 years after 75 years of age if life expectancy is > 4 years United States Preventative Services Task Force No evidence of benefit for women over 75 years of age Mammography screening for women over 70 years with reasonable life expectancy
Breast Cancer Early Detection Guidelines from the American Cancer Society
The aim of breast cancer screening is to detect the cancer early in its asymptomatic phase with the specific goal of reducing breast cancer mortality. Breast self examination is considered optional in all age and breast cancer risk groups based upon a large, randomized trial in Shanghai, China that showed instructions in breast self examination has no effect on reducing breast cancer mortality. If a woman chooses to perform periodic breast self-examination, she may review technique instructions at the Susan G. Komen website for breast cancer. A clinical breast examination performed by a physician during a womans periodic health exam provides an opportunity to discuss with the patient the importance of early breast cancer detection. It is also a chance to emphasize to the patient the importance of an awareness of a family history of breast and ovarian cancers in first and second-degree relatives on both maternal and paternal sides. Breast mammography has been proven consistently in randomized trials to reduce breast cancer mortality by up to 30% although a Cochran Review concluded that it might decrease it by only 15%. There is no consensus on when to start mammography screening and how often. Established guidelines from different countries and medical organizations recommend yearly to biennial mammograms starting at 40 to 50 years of age. The American Cancer Society specifically recommends annual mammogram starting at the age of 40. Screening mammography for women up to 70 years of age is widely recommended. There is insufficient data to recommend for or against routine mammography screening in women over 70 years of age because no patients older than 74 years and few patients between 70 and 74 years were enrolled in randomized trials of mammography screening. When deciding on routine mammography screening for women over 70 years of age, factors such as the womans comorbid conditions, functional status, bone mineral density, interest in preventive care and willingness to accept the potential harm of screening, such as false positives, should be considered.
American Joint Commission on Cancer TNM Staging System In situ Stage 0 - cancer is confined to within the duct or lobules of the breast and has not broken through the basement membrane Lobular carcinoma in situ Ductal carcinoma in situ Local or Early Disease Stage I the cancer is confined to the breast Stage II the cancer has spread to lymph nodes on the same side (ipsilateral) of the breast Locally Advanced Disease Stage III the cancer has spread to superficial structures of the chest wall or there is involvement of ipsilateral internal mammary lymph nodes (near the breast bone) Advanced Disease Stage IV metastasis to the liver, lung, bone, brain
The purpose of radiation therapy is to optimize local control of the breast cancer after breast conserving surgery. It is often administered in early stage breast cancer because it reduces the risk of local recurrence from 26% to only 7% and it improves overall survival. Radiation is also administered to patients with metastatic breast cancer. The purpose in this case is to control the spread of the disease and relieve symptoms such as bone pain in the case of bone metastasis.
Hormonal Therapy for TreaAng Breast Cancer IndicaAons Aromatase Inhibitors Inhibits estrogen synthesis Anastrozole Letrozole Exemestane (steroidal) Postmenopausal ER/PR + breast cancer Exemestane is indicated as second line therapy amer tamoxifen failure Side Eects/ConsideraAons Headache, hot ushes, vaginal dryness -occurs less frequent than tamoxifen Myalgias/arthralgias, Osteoporosis Fractures Baseline Bone Mineral Density (BMD) measurement: - consider calcium + vitamin D and bisphosphonate if BMD is low Estrogen Receptor Antagonist Down regula:on of estrogen receptors Fulvestrant Second line therapy amer failure with tamoxifen or aromatase inhibitors Available as intramuscular injec:on Headaches, nausea, vomi:ng, backache, injec:on site reac:on
Patients diagnosed with primary invasive breast cancer should have their estrogen and progesterone receptor status determined. About 70% of breast cancers are estrogen and/ or progesterone receptor positive and the frequency rises with increasing age. All patients with positive hormonal receptor status should receive adjuvant hormonal therapy regardless of their age, menopausal status, HER-2 receptor status, or whether or not the patient will be receiving adjuvant chemotherapy.
Copyright 2011 American Society of Consultant Pharmacists
Systemic chemotherapy is indicated as adjuvant therapy for high-risk breast cancer patients after surgery or for the treatment of metastatic breast cancer. The administration of adjuvant polychemotherapy and tamoxifen reduces the odds of breast cancer recurrence and death in all age groups younger than 70 years of age. There are many available chemotherapy regimen options for the treatment of breast cancer. An anthracycline-based regimen has been shown to decrease mortality by 38% in women younger than 50 years of age and 20% in women between 50 and 69 years of age. The addition of a taxane to an anthracycline regimen decreases the mortality rate by another 1.5%. The choice of a chemotherapy regimen depends on the side effects profile of the specific regimen and patient tolerability based upon their comorbid conditions.
HER-2 Positive and Epidermal Growth Factor (EGFR) Over Expressing Breast Cancer
Characteristics of HER-2 Positive Breast Cancer More aggressive clinical course Increased risk of metastasis Reduced response to chemotherapy Higher probability of disease recurrence Shortened overall survival (median survival time halved compared to HER-2 negative patients ( 3 years versus 6 to 7 years) Poorer prognosis Trastuzumab Humanized monoclonal antibody that binds selectively to the extracellular domain of HER2 Degrades HER2 receptor Promotes antibody dependent cellular toxicity Induces apoptosis Inhibits angiogenesis Affect tumor growth Additive or synergistic effect with various chemotherapy agents Indications: Adjuvant therapy in early stage breast cancer and metastatic breast cancer that demonstrates HER2 over expression Side Effects: Infusion related reactions; fever and chills Premedicate with acetaminophen and diphenhydramine
HER-2 Positive and Epidermal Growth Factor (EGFR) Over Expressing Breast Cancer
Nausea, vomiting, diarrhea Arthralgia, myalgia Abdominal pain, chest pain, Increased risk of cardiotoxicity in conjunction with doxorubicin Monitor cardiac ejection fraction Lapatinib Oral dual tyrosine kinase inhibitor targeting both HER1 and HER2 receptors Indications: Administered in combination with capecitabine for advanced or metastatic breast cancer that over expresses HER2 after failure with other therapies Side Effects: Nausea, vomiting, diarrhea Hand foot syndrome Administration do not take with food. Take 1 hour before or after a meal. Do not eat grapefruit or drink grapefruit juice when taking this drug. The EGFR, or otherwise known as the epidermal growth factor receptor, family of receptors includes four receptors: HER1 (also known as EGFR), HER2, HER3, and HER4. In 20% to 30% of breast cancers, the HER2 gene is amplified meaning there are excess copies of the gene and the HER2 protein is over expressed meaning there is excess production of the protein. Amplification of HER2 signifies a more aggressive clinical course with poorer prognosis and shortened survival. EGFR or HER1 is over expressed in 27% to 30% of breast cancers.
HER-2 Positive and Epidermal Growth Factor (EGFR) Over Expressing Breast Cancer
Trastuzumab is a humanized monoclonal antibody that binds selectively and with high affinity to the extracellular domain of HER2. The mechanism of trastuzmab is not well understood but it is thought that it decreases expression of HER2 from the cell surface, induces antibody dependent cellular cytotoxicity, inhibits angiogenesis, and induces apoptosis. In metastatic breast cancer with overexpression of HER2, trastuzumab single agent produces 26% response rates and response rates increases to 63 to 79% when it is combined with other chemotherapy agents such as paclitaxel or doxorubicin. Trastuzumab has been shown to improve disease free survival and overall survival when it is administered with chemotherapy as adjuvant therapy for early stage breast cancer. The most common toxicity associated with trastuzumab is an infusion related reaction that manifests as fever and chills which occurs with the first dose and improves with subsequent doses. Congestive heart failure can develop with trastuzumab alone or in combination with paclitaxel or docetaxel and especially with an anthracycline. Patients should be monitored for signs and symptoms of cardiac dysfunction while on trastuzumab therapy. Lapatinib is available as an oral tablet. It is a dual tyrosine kinase inhibitor that targets both EGFR and HER2 receptors. Lapatinib is indicated to be administered with capecitabine after a patient has failed first line therapy for both advanced and metastatic breast cancer that over expresses HER2. The most common side effects are due to both lapatinib and capecitabine and include nausea, vomiting, diarrhea and hand foot syndrome.
Comments and Recommendations Non-pharmacologic therapy: cooling strategies such as using air conditioning and fans, wearing open weave cotton clothing to allow circulation. Avoid hot, spicy foods, drinking warm liquids or alcohol. Pharmacologic therapy: venlafaxine, paroxetine, gabapentin or clonidine. If the patient is on tamoxifen, avoid antidpressants that inhibits CYP2D6 such as paroxetine since tamoxifen needs CYP2D6 for metabolism to its active metabolite.
Vaginal Changes
Dryness, pruritus, increased risk of urinary tract infections, dyspareunia (difficult or painful sexual intercourse). Non-estrogenic vaginal lubricants are recommended to relieve symptoms of dryness and dyspareunia. Systemic estrogen or topical estrogens are not recommended for women with hormone positive breast cancer.
Bony metastasis
When treatment of breast cancer is being considered for elderly women, the patients anticipated life expectancy, co-morbid conditions, functional status and risk for recurrence should be determined before systemic therapy is offered. It is observed that breast cancer in the elderly population has more favorable characteristics. This is evidenced by the cancer expressing either estrogen or progesterone receptor status, having a lower proliferative rate and no expression of the epidermal growth factor receptor or HER2 receptor. About 85% of women who are 65 or older are estrogen receptor positive and more than 63% are progesterone receptor positive. Adjuvant hormonal therapy with either tamoxifen or an aromatase inhibitor should be considered for older women with either positive estrogen or progesterone receptors.
In the last 20 years, the treatment of breast cancer has advanced significantly. Breast cancer mortality is decreasing in the Western world because of advances in treatment options. Pharmacists have an opportunity to be more involved in the care of patients with breast cancer and provide medication counseling due to the availability of oral chemotherapy agents and the need for supportive care issues such as hot flushes, osteoporosis and side effects of chemotherapy
Mortality An estimated 12,920 deaths in 2009 7,200 in males 5,490 in females Mortality is higher in males than females
It is estimated that about twenty two thousand new cases of primary tumors of the brain and other nervous systems will be diagnosed and about thirteen thousand deaths will occur in the United States in 2009. Brain tumors account for 85 to 90% of all primary central nervous system tumors. In children, it is the second most common form of cancer after leukemia. In adults, primary brain tumors commonly occur in the fifth and sixth decades of life. The incidence of primary brain tumors is higher in whites than blacks and mortality rate is higher in males than females. Brain tumors may be classified as primary or secondary tumors. Primary brain tumors are cancers that originate in brain tissues and are named for type of cells or the location of the brain in which they begin. Secondary brain tumors, or otherwise known as metastatic brain tumors, are cancers that originated from another part of the body and have spread to one or more parts of the brain. The cells from metastatic tumors are the same as the cells from which the cancer originated originated, for example, metastatic breast or lung cancer. Secondary brain tumors occur more frequently than primary brain tumors.
Copyright 2011 American Society of Consultant Pharmacists
Prognostic Factors
Astrocytomas Favorable Prognostic Factors The grade of the tumor Age less than 50 years Good performance status Intact neurological function Resectability of the tumor
CNS Lymphoma Favorable Prognostic Factors Age less than 60 years Single, well-circumscribed tumor Absence of immunodeficiency Absence of meningeal or peri-ventricular tumor Diffuse mixed and small noncleaved cell lymphoma In determining prognosis for patients diagnosed with gliomas, good prognostic factors include younger age, good performance status, low grade tumors, intact neurological function and complete resection of the tumor. Glioblastoma, which is a grade 4 aggressive astrocytoma, carries the worst prognosis of all the different types of gliomas. Good prognostic factors for primary CNS lymphoma include single, solitary tumors, age less than 60 years and absence of immunodeficiency. The subtype of CNS lymphoma that does well is diffuse mixed and small noncleaved cell lymphomas. Patients with large immunoblastic and large noncleaved or cleaved lymphomas have worse prognosis.
Treatment Options
Astrocytoma Low-Grade (Grade I and II) Surgery Patients with large lesions and mass effect Radiation Adjuvant therapy after surgery Chemotherapy Role of adjuvant chemotherapy is under investigation Temozolomide is an option High Grade (Grade III and IV; anaplastic astrocytoma and glioblastoma multiforme or malignant astrocytic glioma) Surgery Maximal debulking while minimizing neurologic deficits Radiation Adjuvant therapy after surgery Prolongs survival compared to supportive care alone after surgery Chemotherapy Temozolomide Oral alkylating agent Good CNS penetration Good option for patients older than 70 years who may not tolerate radiation therapy Carmustine (BCNU) Biodegradable polymer (Gliadel wafer) PCV (procarbazine, CCNU (lomustine), vincristine)
Copyright 2011 American Society of Consultant Pharmacists
Treatment Options
Treatment options for astrocytomas include surgery, radiation and chemotherapy. Surgical resection of the brain tumor is recommended for both low grade and high grade astrocytomas. The goal of therapy is to completely remove as much of the tumor as possible while striving to preserve neurologic function at the same time. Radiation has a major role in the treatment of astrocytomas. In low-grade tumors, radiation has been shown to extend the time to recurrence but it has not been shown to improve overall survival. On the other hand, in anaplastic astrocytoma, adjuvant radiation therapy after surgery has been shown to prolong survival. In patients with glioblastomas, the addition of radiation to surgery increases survival from 3 to 4 months to 7 to 12 months. The role of chemotherapy for low-grade astrocytomas and anaplastic astrocytoma is still under investigation. Currently, temozolomide is an option for low-grade astrocytomas over the combination PCV chemotherapy regimen because it is associated with less toxicity. In patients with anaplastic astrocytomas there is no standard treatment after surgery. The role of chemotherapy after surgery is controversial because study results in this patient population are conflicting with some studies demonstrating survival benefit and others do not. Radiation with concomitant and adjuvant temozolomide or adjuvant temozolomide alone are acceptable options in patients with anaplastic astrocytoma. For glioblastomas, adjuvant temozolomide with radiation has convincingly shown benefit with median survival increased by 2 and a half months and 2-year survival by 16.1%. Temozolomide is considered to be the standard of care for glioblastoma multiforme based upon this data. Temozolomide is an oral alkylating agent that has good CNS penetration. It is a viable alternative for patients who are older than 70 years of age in whom radiation has shown little survival benefit with much toxicity. Another chemotherapy approach for glioblastoma involves the implantation of biodegradable polymers containing carmustine, known as Gliadel wafers, into the tumor bed after surgical resection with radiation therapy. The carmustine is released slowly over several weeks to kill any residual tumor cells. The combination PCV chemotherapy regimen is an option for patients with recurrent anaplastic astrocytoma or glioblastoma multiforme.
Copyright 2011 American Society of Consultant Pharmacists
Treatment Options
Primary CNS Lymphoma High-dose methotrexate prior to radiation therapy Dose is > 3.5 gm/m2 Median survival to 23-42 months Currently is the standard therapy Whole Brain Irradiation Steroids 40% response rate Transient effect on the tumor and recurrence commonly occurs Avoid administration prior to biopsy due to difficulty in histology interpretation of the tumor after the steroid The main treatment for primary CNS lymphoma involves the combination of high-dose methotrexate chemotherapy followed by radiotherapy. Chemotherapy has been shown to prolong time to tumor progression and prolong median survival compared to radiation alone. Whole brain radiation may be offered after systemic chemotherapy. When CNS lymphoma is being considered in the differential diagnosis of a brain tumor, administration of a corticosteroid should be avoided because it may eradicate the lymphoma lesion and makes it difficult to diagnose the disease.
Symptom Seizures
Comments and Recommendations Initiate antiepileptic drugs in patients who presents with seizures. Avoid seizures medications that induce CYP450 enzymes if possible to prevent drug interaction with chemotherapy. No evidence to recommend initiation of prophylactic seizure medication in gliomas if a patient has not had a seizure
Peri-tumor edema
Initiate corticosteroids. Monitor for steroid side effects. Cushings syndrome and steroid induced myopathy may occur if a patient is on prolonged high doses of corticosteroid therapy. Consider prophylactic antibiotics for pneumocystis jiroveci. Prevent osteoporosis and compression fracture from long term steroid therapy with vitamin D, calcium supplements and bisphosphonates. Furosemide and mannitol may also be used to treat edema
Symptom
Comments and Recommendations Venous thromboembolism may occur in patients with malignant gliomas in the leg and pelvic veins. The cumulative incidence is 20 to 30%.
Venous thromboembolism Anticoagulation therapy with low molecular weight heparin is indicated unless a patient has intracerebral hemorrhage or other contraindications. Fatigue May initiate modafinil or methylphenidate Renal toxicity maintain good hydration, alkalinize the urine to maintain pH above 7. Discontinue NSAIDS, avoid ascorbic acid or drinking orange juice or grapefruit juice which may acidify the urine. Myelosuppression and mucositis - administer leucovorin rescue Nausea and vomiting - provide anti-emetics Myelosuppression, monitor for neutropenic fever. Temozolomide Side Effects Initiate Pneumocystis carinii pneumonia prophylaxis for patients receiving therapy for glioblastoma multiforme. Provide antiemetics if needed.
In summary, primary brain tumors account for 2% of all cancer malignancies. Treatment options for brain tumors include surgery, radiation therapy, chemotherapy or a combination of these modalities. The specific type of therapy for each type of tumor varies due to different sensitivities and response rate of the tumors. The role of a pharmacist in the treatment of these tumors is to be knowledgeable with the management of side effects and symptoms related to either drug therapy or the disease state.
References
For additional information, see: Cancer Statistics Jemal A SR, Siegel R. et al. Cancer Statistics, 2009. CA Cancer J Clin 2009, July/August Lung Cancer Gridelli C, Rossi A, Maione P. Challenges in treating older non-small lung cancer patients. Ann of Oncol 2008;19 (Suppl 7):vii100-vii113 Gridelli C, Langer C, Maione P, et al. Lung cancer in the elderly. J Clin Oncol 2007;25:1898-1907 Herbst RS, Heymach JV, Lippman SM. Lung Cancer. NEJM 2008; 359: 1367-80 Herbst RS, Sandler RA. Bevacizumab and erlotinib: A promising new approach to the treatment of NSCLC. Oncologist 2008;13:1166-1176 Molina JR, Yang P, Cassivi SD, et al. Non-small cell lung cancer: Epidemiology, Risk Factors, Treatment, and Survivorship. Mayo Clin Proc 2008;83(5):584-594 NCCN. Lung Cancer. Practice Guidelines in Oncology. V.2.2009. Accessed at www.NCCN.org Sher T, Dy GK, Adjei AA. Small cell lung cancer. Mayo Clin Proc 2008;83(3):355-367
References
Smith RA, Cokkinides V, Brawley OW. Cancer Screening in the United States 2009: A review of current American Cancer Society guidelines and issues in cancer screening. CA Cancer J Clin 2009,59:27-41 Walker S. Updates in non-small cell lung cancer. Clin J Onco Nurs 2008;12(4):587-596 Breast Cancer Balducci L. Treating elderly patients with hormone sensitive breast cancer: What do the data show? Cancer Treatment Reviews 2009;35:47-56 Harmer V. Breast cancer-related lymphedema: risk factors and treatment. Br J of Nurs 2009;18(3):166-172 Loprinzi CL, Wolf SL, Barton DL, Laack NN. Symptom management in premenopausal patients with breast cancer. Lancet Oncol 2008;9:993-1001 NCCN. Breast Cancer. Practice Guidelines in Oncology. V.1.2009. Accessed at www.NCCN.org Muss HB. Adjuvant treatment of elderly breast cancer patients. The Breast 2007;16:S159-165 Nielsen DL, Andersson M, Kamby C. HER2 targeted therapy in breast cancer. Monoclonal antibodies and tyrosine kinase inhibitors. Cancer Treatment Reviews 2009;35:121-136 Smith RA, Cokkinides V, Brawley OW. Cancer screening in the United States 2009: A review of current American Cancer Society guidelines and issues in cancer screening. CA Cancer J Clin 2009,59:27-41 Thomsen A, Kolesar JM. Chemoprevention of breast cancer. Am J Health-System Pharm 2008;65:2221-8
References
Brain Tumors Bhagavathi S, Wilson JD. Primary Central Nervous Lymphoma. Arch Pathol Lab Med 2008;132:1830-1834 Buckner JC, Brown PD, Oneill BP, et al. Central Nervous System Tumors. Mayo Clin Proc 2007;82(10):1271-1286 NCCN. Central Nervous System Cancers: Practice Guidelines in Oncology. V.1.2009. Accessed at www.NCCN.org Wen PY, Kesari S. Malignant Gliomas in Adults. NEJM 2008;359:492-507
By the end of this Review Concept you should be able to: Cite the epidemiology for colorectal cancer. Identify the risk factors for colorectal cancer. Describe the recommended screening procedures for colorectal cancer. List the most common symptoms associated with colorectal cancer and describe how they may differ depending on the location of the primary tumor. Describe the role of surgery and chemotherapy in managing colorectal cancer. Describe the epidemiology and manifestations of prostate cancer. Describe options for the early and late treatment of prostate cancer. Describe the epidemiology for pancreatic cancer. Describe the signs and symptoms and complications associated with pancreatic cancer. Describe the treatment options for pancreatic cancer.
Colorectal Cancer
Epidemiology Third most frequently diagnosed cancer in men and women Estimated 146,940 new cases of colorectal cancer in 2004 106,370 colon cancer cases 40,570 rectal cancer cases Estimated 56,730 colorectal deaths in 2004 Mortality decreased over past 30 years
Cancers of the rectum and colon account for eleven percent of all cancers and ten percent of all cancer related deaths in men and women. It is the third leading cause of cancer-related deaths after lung and breast cancer. It is estimated that in 2004 there will be approximately 147,000 cases of newly diagnosed colorectal cancer, about 106,000 of which will be colon cancer and 41,000 of which will be rectal cancer. The good news is that the mortality rate for colorectal cancer has been decreasing during the past 30 years due in part to screening recommendations and better treatment modalities.
Genetic Mutations K-ras mutations Deleted Colon Cancer Gene (DCC gene) Loss of chromosome 17p Mutation mismatch repair genes Inactivation of tumor suppressor genes
Individuals at High Risk of Developing Colorectal Cancer HNPCC FAP IBD Colo-rectal Cancer Colonoscopy every 1 2 years Colonoscopy every year Sigmoidoscopy every year Colonoscopy every 1 2 years Colonoscopy every 3 5 years Star:ng at 20 30 years Star:ng at 40 years Star:ng at puberty 8 years amer onset of pancoli:s or 15 years amer onset of lem-sided pancoli:s One year amer treatment
Tumors of the Transverse and Descending Colon: Left-Sided Lesions Obstructive symptoms Cramping, constipation Diarrhea Bowel changes Bleeding
Tumors of the Cecum and Ascending Colon: Right-Sided Lesions No significant changes in bowel habits Watery diarrhea Occasional abdominal pain
The majority of colorectal cancer occurs in the distal portion ofthe colon and the rectum. Sixty percent of cancers are located in the left side of the colon. Generally the disease is asymptomatic until it either becomes quite large or penetrates through the bowel mucosa. Two thirds of patients with colorectal cancer do not seek medical attention until the disease is more advanced when symptoms are present. Symptoms of more advanced colorectal cancer include bleeding through the rectum, which is visible in the stool; changes in bowel habits, including constipation and occasional diarrhea. Nausea, vomiting, weight loss and pain may indicate bowel obstruction or perforation. Left-sided colonic lesions tend to cause more obstructive symptoms, while right-sided lesions can cause abdominal discomfort and slow bleeding that later shows up as anemia. The most common site of metastasis for colorectal cancer is the liver or the lungs. Hepatomegaly, jaundice, pruritis are associated with liver metastasis.
Colorectal Cancer Staging System MAC A / B1 B2 B3 C1 C2/C2/C3 D Dukes A B B C C TNM 0 Stage I IIA IIB IIA IIB IV 60-80% 59.8% 42% 8% 90% 5-year survival
Treatment of Stage I-III Rectal Cancer Stage I Surgery Stage II-III Surgery Adjuvant radiation with 5-FU Adjuvant chemotherapy Leucovorin and Fluorouracil Fluorouracil(5-FU)/leucovorin/Oxaliplatin (FOLFOX)
The goals of therapy for stage IV metastatic colorectal cancer are to extend survival and improve symptoms. The primary treatment modality for stage IV disease is chemotherapy. There are many chemotherapy regimen options available and the choice of which regimen to administer is based upon the toxicity profile of the regimen and the type and timing of prior chemotherapy the patient has received. In general, 1st-line chemotherapy may include the FOLFOX or the FOLFIRI regimen or the use of the monoclonal antibody bevacizumab and a 5-FU containing regimen. For patients who may not be able to tolerate intensive first line therapy, alternative chemotherapy agents such as capecitabine or 5-FU and leucovorin may be considered.
Prostate Cancer
Epidemiology Most common cancer in males Estimated 230,110cases in 2004 Second most common cause of cancer related death in men Estimated 29,900 deaths in 2004 Risk Factors Age Race Family history Diet Occupation Prostate Cancer Screening Digital Rectal Exam (DRE) Lumps, hardness, inability to move the prostate indicate further need for evaluation Prostate Specific Antigen Screening, determine prognosis, detect recurrence, monitor response to therapy Factors that increase PSA DRE Biopsy Benign Prostatic Hypertrophy Prostatitis
Copyright 2011 American Society of Consultant Pharmacists
Prostate Cancer
Factors that decrease PSA Finasteride Saw palmetto Surgery Radiation Hormonal Therapy Following lung cancer, prostate cancer is the 2nd-leading cause of cancer death in men. It is the second most common malignancy in American men. It is estimated that 230,110 new cases of prostate cancer will be diagnosed in 2004 and an estimated 29,900 men will die ofthis disease. The probability of developing prostate cancer increases with age. In men less than 65 years of age, about 1 in 10 will be diagnosed with prostate cancer. Between the age of 65 years to 74 years, 2 in 10 men will be diagnosed with prostate cancer. The incidence is highest in men over 75 years of age where 7 in 10 men will be diagnosed with prostate cancer. Prostate cancer affect African Americans fifty percent more often than white Americans. The risk is lowest for Asians. Individuals with a family history of prostate cancer have a higher risk of developing prostate cancer, especially at a younger age. The correlation between prostate cancer and diet is less clear; however, it is thought that a high fat diet may increase the risk of prostate cancer. Occupational exposure to industrial chemicals may also predispose a man to greater risk of prostate cancer. Prostate cancer screening involves 3 modalities, a digital rectal exam, a serum prostate specific antigen level, and a transrectal ultrasound. A digital rectal exam allows the physician to feel for lumps or hardness of the prostate. If these signs are present, further evaluation tests are needed. The prostate specific antigen is a glycoprotein secreted by epithelial cells of the prostate, the purpose of which is to liquify seminal secretions. The PSA is specific for prostate abnormalities but not for prostate cancer. The PSA may be used to screen for possible prostate cancer, to predict prognosis, to detect recurrence after therapy, and to monitor a patients response to therapy.
Prostate Cancer
Besidesprostate cancer, ejaculation and prostate manipulation may increase the PSA level. Therefore this test should be performed 48 hours after these manipulations. The 5-alpha reductase inhibitor, finasteride, and saw palmetto have been shown to decrease PSA levels; therefore, a thorough patient medication history should be obtained prior to obtaining PSA levels.
Interpretation of PSA Values 0-4 ng/ml 4-10 ng/ml > 10 ng/ml Normal, age non-specific Borderline Suspicious for malignancy Age Specific Reference Ranges Age 40-49 years 50-59 years 60-69 years 70-79 years PSA velocity Measures the change of the PSA values over time A higher doubling time of the PSA value correlates with a high PSA velocity and a higher risk of having prostate cancer PSA density Used to differentiate high PSA levels in men with a large prostate with prostate cancer PSA value divided by the prostate volume as measured by a transrectal ultrasound Normal PSA 0-2.5 ng/ml 0-3.5 ng/ml 0-4.5 ng/ml 0-6.5 ng/ml
Staging of Prostate Cancer Stage A (I) Stage B (II) Stage C (III) Stage D (IV) Tumor discovered incidentally on histologic exam Tumor palpable on digital rectal exam Tumor extending beyond the prostate but conned to within the pelvis Disseminated tumor
A rectal examination of the patient reveals a prostate that isharder than normal. The serum Prostate Specific Antigen or PSA is elevated in most men with prostate cancer, even prior to symptoms, and is often used to assist in detectingthe disease in men who are asymptomatic. A transrectal ultrasound with a guided needle biopsy of the prostate through the rectum or perineum will confirm the diagnosis. A bone scan or CT of the abdomen is performed if the patients has signs of metastatic disease such as bone pain or jaundice. While a digital rectal exam is sufficient to evaluate the local extent of the tumor, staging is necessary to characterize the extent of the disease and determine the most appropriate type of treatment. The first staging involves determining the degreee of differentiation of the tumor called the Gleason Score. The higher the grade or score, the less differentiated the tumor is and the poorer the prognosis for the patient. The tumor is then staged based upon its size, lymph node involvement, and metastasis. In stage A disease the tumor is still small and is diagnosed incidentally on histologic examination. In stage B disease the tumor is palpable on digital rectal examination. In stage C the tumor has spread beyond the wall of the prostate but it is still confined to the pelvis. In stage D there is widespread dissemination of the disease.
This slides provides information on the different LHRH agonists and antiandrogens that are used in practice for the treatment of prostate cancer. Common doses and side effects are also provided for your reference.
Prostate Cancer Surveillance Watchful WaiAng DeniAve Local Therapy Clinical exam, DRE, & PSA every 6 months DRE & PSA every 6 months, repeat prostate biopsy 1 year amer diagnosis PSA every 6 months for 1st 5 years, then annually Annual DRE
History, physical examina:on, DRE, PSA every 3 to 6 months Bone scan when pa:ents develop symptoms or PSA rises very quickly
Pancreatic Cancer
Epidemiology Estimated 31,860 new cases will be diagnosed in 2004 Estimated 31,270 deaths will occur in 2004 Accounts for 2% of all cancer diagnosis Accounts for ~ 5% of all cancer related deaths Fifth leading cause of adult deaths from cancer Only 1 4% of patients will be alive 5 years after diagnosis Risk Factors Age (> 50 years, frequently in 7th & 8th decades) Tobacco smoking Family History Race (African Americans) Diabetes Pancreatitis Diet Industrial chemical exposure Molecular Features of Pancreatic Cancer K-ras mutations HER2/neu overexpression p16, p53 mutations
Pancreatic Cancer
Pancreatic cancer is the 5th most common cause of cancer related deaths in the United States. It is predicted that there will be 31,860 cases of newly diagnosed pancreatic cancer and almost the same number of deaths in 2004. Only 1 to 4% of patients diagnosed with pancreatic cancer will be alive at 5 years because the disease is very aggressive, it is very difficult to diagnose, and there are no effective systemic treatment options for this cancer. Pancreatic cancer rarely occurs before 50 years of age. It is commonly diagnosed in the seventh and eighth decades of life. There is firm evidence linking smoking and pancreatic cancer and patients with a family history of pancreatic cancer is at high risk for developing the disease. The incidence in African-Americans has been found to be 30% higher than among white Americans. There has been some correlation found between diabetes, pancreatitis and pancreatic cancer, although this association is a topic of great debate. There have been no clear dietary risk factors for pancreatic cancer. However, there may be a positive association between pancreatic cancer with meat and carbohydrate consumption, and dietary fat and increased body mass index has been implicated in experimental models. Exposure to chemical such as pesticides, ionizing radiation, betanaphthylamine and benzidine is also associated with an increased risk of pancreatic cancer. Mutations of K-ras proto-oncogene occurs in about 90% of pancreatic cancers. Overexpression of the HER2/neu protein has also been found along with mutations of the p16 and p53 gene.
Presenting Signs and Symptoms Jaundice Pruritis Phlebitis Pain in the upper abdomen Nausea, vomiting Diarrhea, belching, bloating, hiccups Constipation Loss of appetite, weight loss Mild diabetes Depression
Diagnostic Workup History and Physical exam Jaundice, abdominal masses, enlarged gallbladder, enlarged liver, ascites, enlarged lymph nodes, phlebitis Ultrasonagraphy or CT Scan of the abdomen to identify mass Endoscopic Retrograde Cholangiopancreatography (ERCP) Fine needle aspiration biopsy CA 19-9 CBC, serum bilirubin Serum Alkaline Phosphatase
Pancreatic Cancer
Staging Resectable Locally Advanced Metastatic Treatment Options for Pancreatic Cancer: Surgery Pancreaticoduodenectomy (Whipple Procedure) Biliary Stenting Radiation Radiation concurrent with fluorouracil postoperatively Chemotherapy Fluorouracil Gemcitabine Resectable Disease Surgical resection Locally Advanced Disease Radiotherapy and Chemotherapy Adjuvant Chemotherapy Fluorouracil or Gemcitabine Metastatic Disease Chemotherapy Fluorouracil Gemcitabine
Pancreatic Cancer
The most widely accepted and utilized staging system for pancreatic cancer is the Clinical Staging System based upon 3 classifications. The first classification is if the cancer is resectable or borderline resectable. The second classification is if the cancer is locally advanced, and the third is if the cancer is disseminated. Treatment options for pancreatic cancer include surgery, radiation therapy and systemic chemotherapy. Surgical procedure involving resection of the tumor and the surrounding pancreatic tissue. It is the only potentially curative treatment option for pancreatic cancer. Radiation therapy concurrent with fluorouracil chemotherapy should be administered following surgical resection in all patients. Fluorouracil has been the most widely used chemotherapy agent in the treatment of pancreatic cancer in the past few decades. Today, however, gemcitabine is the current standard of care for patients with locally advanced and metastatic pancreatic cancer.
The goal of therapy for most patients diagnosed with pancreatic cancer is palliation of symptoms and optimization of supportive care. Pain is reported by 75 80% of patients at initial evaluation of the pancreatic cancer and it is described as a dull, fairly constant pain of visceral origin localized to the region of the middle and upper back. Optimal pain management consists of radiation therapy with or without chemotherapy to palliate the pain associated with the pancreatic cancer. Pharmacologic management involves the use of analgesic agents such as opioids or non-steroidal inflammatory agents. An anesthetic block of the celiac plexus may also offer fast and effective pain control that can last for a period of 3 to 4 months. For patients with pancreatic cancer located in the head of the pancreas, obstructive jaundice leads to the diagnosis. Symptoms of obstructive jaundice include pruritis, jaundiced sclera and skin, discolored urine and clay colored stool. Biliary decompression by a surgical bypass or an endobiliary stenting is the technique to resolve this situation. Cachexia and weight loss is associated with weakness, poor quality of life and contributes to depression and increased morbidity. Caloric supplementation and hydration are initial treatment along with pharmacologic intervention with the addition of appetite stimulants such as megesterol acetate and dexamethasone. The addition of pancreatic enzymes for pancreatic insufficiency will improve malabsorption, bloating, diarrhea, and prevents further weight loss in pancreatic cancer patients.
Resources
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