NRS 321 Oncology Class Notes Fall 2024 PDF

Departments of Nursing NRS 321 Pathophysiology – Pharmacology I Class Notes - Oncology – Fall 2024 NRS 321 Pathophysiology - Pharmacology I Basic Principles of Oncology and Cancer therapy Basic principles of oncology: Cancer cell...

Departments of Nursing NRS 321 Pathophysiology – Pharmacology I Class Notes - Oncology – Fall 2024 NRS 321 Pathophysiology - Pharmacology I Basic Principles of Oncology and Cancer therapy Basic principles of oncology: Cancer cell characteristics Oncogenesis and cancer growth Manifestations and diagnostics Exemplar for this section: Colorectal cancer case study Cancer Cell Characteristics Oncogenesis and cancer growth Terms Neoplasia or ‘New growth’ - tissue that exceeds normal growth patterns Benign proliferation: well differentiated cells that appear in a mass. Malignant proliferation: less differentiated cells that can travel from the site of origination to remote sites. Cancer is a malignant neoplasm Cells often do not mature normally (differentiate) to do the “job” the tissue is supposed to do. Lack of apoptosis or programmed cell death Benign Tumor characteristics Contain cells that look like normal tissue cells May perform the function of the tissue but in an altered form Example: may secrete hormones, but the levels secreted are abnormal (over secretion) Grow slowly Surrounded by a fibrous capsule Do not infiltrate, invade, or metastasize Are not harmless - Can damage nearby organs by compressing them Malignant Tumor characteristics Contain cells that do not look like normal adult cells Do not perform normal functions of the tissue May secrete signals, enzymes, toxins, etc. Grow rapidly Lack capsules - sends “legs” into surrounding tissue (the word cancer means “crab” based on these legs) Infiltrate, invade, and metastasize (to distant sites)  Departments of Nursing NRS 321 Pathophysiology – Pharmacology I Class Notes - Oncology – Fall 2024 Can compress and/or destroy the surrounding tissues Malignant tumors Types – Solid or Hematologic Cellular examination required to confirm malignancy Terms: Anaplastic – primitive and undifferentiated cellular appearance In Situ – localized and pre-invasive Growth Properties: Select Cancer cell characteristics Genetic instability results in high numbers of mutations Secrete growth factors and/or have receptors to sustain abnormal growth Lack cell density which typically produces dependent or contact inhibition. Cancer cells continue to grow. Faulty cell-to-cell communication Life span – Immortal cell lines that divide indefinitely Higher telomerase levels maintained  longer telomeres indicates lack of aging Cancer Cell Characteristics: Invasion and Metastasis Cells in a primary tumor develop the ability to escape, travel, and survive in the blood, exit the blood, and develop a secondary tumor. Metastasis Cancer Cell Characteristics: Cell Cycle Normally, the number of cells produced = the number of cells that die. Therefore, the total number of cells in the body remains constant. In cancer, growth fraction (dividing:resting cells) increases and doubling time decreases. Tumor Growth - tumors can be detected when 1 billion cells are present Oncogenesis: The transformation of healthy cells to cancer cells Cancer-Associated Genes  Departments of Nursing NRS 321 Pathophysiology – Pharmacology I Class Notes - Oncology – Fall 2024 Proto-oncogenes – normal genes that can mutate into cancer causing genes. These genes code for normal cell proteins and growth factors, growth factor receptors, transcription factors, etc. Proto-oncogenes mutate to oncogenes. Oncogenes are cancer causing genes. Insertions, deletions, translocations  increased or activated Examples: Philadelphia chromosome and chronic myelocytic leukemia; HER-2/neu gene and breast cancer. Tumor suppressor genes inhibit cell division and suppress cancer formation. Tumor suppressor genes reduce cancer growth. Mutations to this gene remove the inhibition to cancer genesis. Stages of Carcinogenesis A multistep process summarized in three steps Initiation: Exposure to carcinogenic agent. DNA damage and initial mutation occurs. Promotion: Mutated cells are stimulated to divide. Progression: Tumor cells compete with one another and develop more mutations which make them more aggressive, resulting in invasion and metastasis. Host and Environmental Factors Inheritance of genes – breast cancer, ovarian cancer, prostate, and pancreatic cancers are associated with BRCA-1, BRCA-2 Reproductive hormones – Women (breast and ovary), Men (prostate and testis) Obesity and higher cancer mortality rates Immune system can assist in resistance to cancer through surveillance. This is supported by the use of immunotherapy as cancer treatment. Chemical carcinogens – Cigarettes, alcohol. Diet – High fat and red meat, low fiber. Food preservatives Radiation – Ionizing radiation, sunlight Oncogenic viruses – Human papilloma virus (cancer of the cervix), hepatitis B (liver cancer). Vaccines are available! Group I: Class discussion: How do genetics and environmental influences affect individual risk of developing cancer?  Departments of Nursing NRS 321 Pathophysiology – Pharmacology I Class Notes - Oncology – Fall 2024 Manifestations and diagnostics Manifestations of Cancer Site of the cancer determines many of the clinical manifestations. Example: Lung cancer produces manifestations of pulmonary dysfunction. Once there is metastasis, other symptoms develop based on the site of metastasis. Clinical manifestations: Local Effects of Tumor Growth on tissue integrity Compression of adjacent structures Hollow organs – compression of the viscera and production of obstructions Blood vessel invasion Bleeding, hemorrhage Effusions – production of fluid into body spaces Sites: Pleural (lung), pericardial (heart), peritoneal (abdomen) Manifestations based on the site of the effusion Clinical manifestations: Systemic Manifestations of Cancer Anorexia – cachexia syndrome: Lack of appetite (anorexia) with weight loss and protein wasting. More common in children and elderly. The syndrome worsens as cancer advances. Fatigue and sleep disturbances – most common side effects in cancer patient. Fatigue is not improved with rest. Sleep disturbances include poor sleep quality and night time waking. Anemia – Low red blood cell counts related to blood loss, lack of red blood cell production, and nutritional issues. Chemotherapy can affect blood counts. Paraneoplastic Syndromes Abnormal alterations produced by tissues unrelated to the tumor or metastases Cancer cells produce hormones or hormone-like proteins that affect other tissues ACTH (produces Cushing syndrome) Cancer cells produce proteins that produce clotting. Neurologic disorders – produce dysfunction of nerve transmissions. Diagnostics: Screening and prevention Observation – skin cancers, oral cancers Palpation – breast cancer, prostate cancer  Departments of Nursing NRS 321 Pathophysiology – Pharmacology I Class Notes - Oncology – Fall 2024 Laboratory testing – multiple methods Screening Early detection for improved outcomes Breast cancer – mammogram Cervical cancer – Pap smear Colorectal exam – occult blood Prostate – PSA Cancer Diagnostics Tumor markers – detect antigens produced by or as a response to a tumor. Not as effective in screening for cancers, but more effective to monitor progression. PSA prostate-specific antigen, and CA125 for ovarian cancer Cytologic studies – examine tissue and cells microscopically for abnormal cells. Pap (Papanicolaou) test for cervical cancer Cancer diagnostics Tissue biopsy – removal of tissue for microscopic examination. Fine needle aspiration for palpable tumors such as breast cancer. Excisional biopsies for entire tumor removal. Immunohistochemistry – identification of cell markers on cancer cells is used to determine the original site of a cancer or for treatment options for best success. Estrogen receptor on breast cancer determine the use of antiestrogen therapy Diagnostics: Grading and Staging Grading: Microscopic examination of differentiation and number of mitoses (grades I – IV) I = well differentiated; IV = poorly differentiated Staging: Clinical, radiographic, surgical examination to determine the extent and spread. Is important for treatment and prognosis. TNM: T 1–4 = tumor size, N 0–3 = lymph node involvement, M0–1 = metastasis Cancer Treatment Surgery – will be discussed in clinical courses Radiation therapy – will be discussed in clinical courses Chemotherapy  Departments of Nursing NRS 321 Pathophysiology – Pharmacology I Class Notes - Oncology – Fall 2024 Hormone and anti-hormone therapy Biotherapy Childhood Cancer Usually hematologic, nervous, soft tissues, or bone. Incidence is greatest during the first years of life. No early warning signs or screening tests. Treatments produce late sequelae in long term survivors Case Study The faculty will demonstrate how students will present the case, the electronic resource selected for the case study patient, and the assigned medication associated with the case study. Colorectal cancer information pertinent to the case study follows Group II: Class discussion of colorectal case study. (Everyone should read the case study) Group III: Class discussion: Verbal critique of the electronic resource Colorectal cancer Incidence increases with age 72% of cases are in those in their 40’s Increased risk with: Family history Crohn’s disease or ulcerative colitis Familial adenomatous polyposis – autosomal dominant that causes multiple polyps Diet is likely (high refined sugar, high fat, lack of fiber) Prevention – ASA may protect against some types of colorectal cancer Pathophysiology Colon cancer is typically preceded by polyps Adenomatous polyps – benign from the intestinal mucosal epithelium. Most colorectal cancers begin as benign polyps. Tubular adenomas (smooth sphere on a stalk) comprise 65% of large bowel adenomas (above picture) Villous adenomas (uneven surface) – 10% of adenomas of colon. More likely to contain malignant cells. Can progress into an invasive carcinoma  Departments of Nursing NRS 321 Pathophysiology – Pharmacology I Class Notes - Oncology – Fall 2024 Clinical manifestations Few, if any symptoms until it has been present for a long time. Then: Bleeding Changes in bowel habits (diarrhea, constipation) Pain (late symptom) Diagnosis – Digital rectal exam, fecal occult blood, barium studies and colonoscopy with biopsy CT scan/MRI for spread Classified using the TNS stages Treatment – Surgical removal, chemotherapy Colorectal cancer – screening Early diagnosis is critical Fecal blood tests (fecal immunochemical test, occult blood, DNA) Sigmoid/colonoscopy – every 10 years or as advised by health care provider All students - Class discussion prompt: Your case study patient’s children ask for recommendations for colon cancer screening for themselves. What will you tell them? R - Burcham – p. 1217, Table 101.4, Recommended screening. Table with screening recommendations can be found at the bottom of the following link: https://www.cancer.org/cancer/colon-rectal-cancer/detection-diagnosis-staging/screening- tests-used.html Chemotherapy - overview Basic Principles of Cancer treatment Cancer: unregulated cellular proliferation Treatment modalities Surgery Radiation Drug therapy Treatment of choice for disseminated cancers (leukemia, disseminated lymphomas, widespread metastases) Classes of Cancer Chemotherapy Drug classes Cytotoxic agents (chemotherapy) Hormones and hormone antagonists Biologic response modifiers  Departments of Nursing NRS 321 Pathophysiology – Pharmacology I Class Notes - Oncology – Fall 2024 Targeted drugs Group IV: Class discussion: Relate one of the assigned chemotherapeutic agents to a concept of cellular development of cancer (not cytotoxic agents). (Consider hormone therapy to cellular development of cancer.) Cancers – Cytotoxic chemotherapy Chemotherapy is toxic to cells that have a high growth fraction (ratio of dividing cells to resting cells). Most common cancers Solid tumors of the breast, lung, prostate, colon, and rectum have low growth fraction and respond poorly to drugs. Rarer cancers Lymphocytic leukemia, Hodgkin’s disease, certain testicular cancers have high growth fraction and respond well to drugs The Growth Fraction and Its Relationship to Chemotherapy The cell cycle Four major phases The growth fraction - Impact of tissue growth fraction on responsiveness to chemotherapy (high growth fraction, more responsive) Tissue Growth fraction and Chemotherapy Chemotherapy drugs are also more toxic to normal tissue with high growth fraction Bone marrow Skin Hair follicles Sperm Gastrointestinal tract Obstacles to Successful Chemotherapy Toxicity to normal cells prohibits the delivery of doses needed to cure. Cure requires 100% cell kill since any remaining cells can proliferate Early detection is not possible (1 billion cells needed to detect a solid tumor). Solid tumors do not respond well to chemotherapy (low growth fractions). Drug resistance can develop. Strategies for Achieving Maximum Benefits From Chemotherapy Intermittent chemotherapy –  Departments of Nursing NRS 321 Pathophysiology – Pharmacology I Class Notes - Oncology – Fall 2024 Allows normal cells to recover Combination chemotherapy - Benefits Suppression of drug resistance Increased cancer cell kill Reduced injury to normal cells – drugs should not have the same toxicities. Strategies for Achieving Maximum Benefits From Chemotherapy Regional drug delivery (reduces systemic toxicity) Intra-arterial – infusion directly into arteries near solid tumors Intrathecal – delivery directly into the central nervous system to bypass the blood brain barrier Other specialized routes – infusions into the bladder, pleural spaces, peritoneal cavities. Major Toxicities of Cancer Chemotherapy Bone marrow suppression Neutropenia Thrombocytopenia Anemia Digestive tract injury Stomatitis/mucositis Nausea, vomiting, diarrhea Alopecia – hair loss (reversible) Hyperuricemia – high uric acid levels can cause renal damage Reproductive toxicity – to germ cells and fetus Local injury from extravasation of vesicants Carcinogenesis later in life Making the Decision to Treat Benefits of treatment must outweigh risks Patient must be given some idea of the benefits of proposed therapy One of these three should be possible: Cure, prolongation of life, palliation  Departments of Nursing NRS 321 Pathophysiology – Pharmacology I Class Notes - Oncology – Fall 2024 Anticancer Drugs I: Cytotoxic Agents Cytotoxic Anticancer Drugs Largest class of anticancer drugs Act directly on cancer cells (and healthy cells) to cause their death About 50% of cytotoxic anticancer drugs are cell cycle phase specific. Cell-Phase Specificity Sequence of events that a cell goes through from one mitotic division to the next Cell-cycle phase–specific drugs Toxic only to cells that are in a particular phase Must be in the blood continuously over a long time Cell-cycle phase–nonspecific drugs Can act during any phase of the cell cycle Dosage, Handling, and Administration Antineoplastic drugs are often mutagenic, teratogenic, and carcinogenic Direct contact can result in local injury Extravasation of vesicants Severe local injury – may need skin grafting Select a good site – implantable port is best Discontinue immediately if extravasation Cytotoxic Agents: Alkylating Agents Mechanism of action Cells are killed by the alkalization of DNA Cell-cycle phase–nonspecific agents Drug resistance is common Toxicities Occur in tissues with high growth fraction Bone marrow, hair follicles, GI mucosa, and germinal epithelium Classes of Alkylating Agents Nitrogen mustards – some of the first chemotherapeutic agents. Cyclophosphamide (Cytoxan)  Departments of Nursing NRS 321 Pathophysiology – Pharmacology I Class Notes - Oncology – Fall 2024 Broad spectrum, most commonly used alkylating agent Is a prodrug, activated in the liver May be given orally (with food) or IV Bone marrow suppression is the primary dose-limiting toxicity. Hydration is necessary since this drug can cause hemorrhagic cystitis Cytotoxic agents: Platinum Compounds Platinum containing drugs Mechanism of action Produce cross linkage in DNA Cell-cycle phase–nonspecific agents Cisplatin (Metastatic testicular/ovarian and bladder cancer) IV administration Dose limiting factor is renal damage – hydration and diuretic therapy Nausea/vomiting most common effect – antiemetics Oxaliplatin (Colorectal cancer) Case study medication Dose limiting toxicity is the development of peripheral neuropathies Cytotoxic Agents: Antimetabolites General mechanisms of action - Inhibit enzyme synthesis/DNA formation – resemble natural metabolites Folic acid analog – block the conversion of folic acid to its active form Methotrexate – S phase specific Mechanism of action – inhibits dihyrofolate reductase (enzyme inhibition) and disrupts synthesis of thymidylate. Multiple toxicities Leucovorin rescue is used for normal cell synthesis of thymidylate Cytotoxic Agents: Antimetabolites Pyrimidine analogs Fluorouracil – S phase specific Solid tumors treatment Mechanism of action – Inhibits thymidylate synthetase and blocks thymidylate synthesis (enzyme inhibition) Toxicities – bone marrow suppression and oral/GI ulceration (mucositis)  Departments of Nursing NRS 321 Pathophysiology – Pharmacology I Class Notes - Oncology – Fall 2024 Cytotoxic Agents: Mitotic Inhibitors Cell phase specific - active during M phase Taxanes Paclitaxel Mechanism of action – inhibits cell division (promotes the formation of stable microtubule bundles) and produces apoptosis. Caution: Severe hypersensitivity reactions – pretreat patient to reduce Dose limiting toxicity - Bone marrow suppression Group V: Class discussion: Relate the mechanism of cytotoxic agents to the cellular development of cancer. Anticancer Drugs II: Hormonal Agents, Targeted Drugs, and Other Non-cytotoxic Anticancer Drugs Hormonal Agents Used primarily for breast cancer and prostate cancer Mimic or block the actions of endogenous hormones Breast Cancer Most common cancer affecting women in the United States Principal treatments Surgery, radiation, cytotoxic drugs, and hormonal drugs Hormonal agent Antiestrogen: Tamoxifen Used for established disease and for decreasing occurrence in high-risk patient Adjuvant therapy after surgery – suppress residual disease Treatment of metastatic disease – using tamoxifen for 10 years halved the rate of mortality for ER positive women. Used to reduce breast cancer development in women at high risk. Tamoxifen Mechanism of action –Blocks ERs (estrogen receptors) and decreases the rate of tumor cell growth. Tamoxifen also activates receptors in certain tissues (increases bone mineral density, reduces LDL, increases HDL,). Tamoxifen is a prodrug. The patient must be ER positive.  Departments of Nursing NRS 321 Pathophysiology – Pharmacology I Class Notes - Oncology – Fall 2024 Adverse effects Most common - Hot flashes, fluid retention, vaginal discharge, nausea and vomiting, menstrual irregularities Rarer – thromboembolism, endometrial cancer Group VI: Class discussion: Discuss education for patients who will be started on tamoxifen. Adjuvant treatments: Trastuzamab Monoclonal antibody Only effective against tumors overexpressing HER2 (human epidermal growth factor receptor) Mechanism of action – Binds to the HER2 and inhibits cell growth and promotes cell death Cardiac toxicity – ventricular dysfunction, congestive heart failure. Flu-like syndrome with infusion that diminishes over time. Prostate Cancer Most common cause of cancer among men in United States Standard treatment of advanced prostate cancer is androgen deprivation Slows disease progression and increases comfort Lower testosterone production Block testosterone receptors with drugs Gonadotropin-Releasing Hormone Agonists: Leuprolide GnRH drugs for prostate cancer Leuprolide Others: Triptorelin, Goserelin, Histrelin Mechanism of action - Suppress production of androgens by the testes Gonadotropin-Releasing Hormone Agonists: Leuprolide Adverse effects Generally well tolerated Hot flashes which decrease with continued use Reduced testosterone – erectile dysfunction, loss of libido, gynecomastia, risk of stroke and myocardial infarction. During initial weeks, testosterone elevations may aggravate bone pain and urinary obstruction  Departments of Nursing NRS 321 Pathophysiology – Pharmacology I Class Notes - Oncology – Fall 2024 Concurrent treatment with androgen receptor blocker can minimize these effects