Chemotherapy (PHAR1059) 2024-2025 PDF
Document Details
Uploaded by SuperiorRadium
George Brown College
2025
PHAR
Tags
Summary
These are lecture notes covering different types of chemotherapy, including antimetabolites, mitotic inhibitors, and topoisomerase inhibitors. The materials detail the general mechanism of action, effects, and adverse events of these chemotherapy treatments.
Full Transcript
ANTINEOPLASTICS Chemotherapy PHAR1059 – 2024-2025 ANTINEOPLASTIC DRUG THERAPY 1. Chemotherapy Cell cycle specific Cell cycle non-specific 2. Hormonal 3. Targeted drug therapy Biological Immunotherapy CAR-T Therapy 4. Supportive Drug Therapy CHEMOTHERAPY...
ANTINEOPLASTICS Chemotherapy PHAR1059 – 2024-2025 ANTINEOPLASTIC DRUG THERAPY 1. Chemotherapy Cell cycle specific Cell cycle non-specific 2. Hormonal 3. Targeted drug therapy Biological Immunotherapy CAR-T Therapy 4. Supportive Drug Therapy CHEMOTHERAPY CHEMOTHERAPY General Mechanism of Action Cytotoxic but not Tumoricidal Cytotoxic A substance that kills cells, including cancer cells. These agents may stop cancer cells from dividing and growing and may cause tumors to shrink in size. Tumoricidal A substance that kills only tumor cells. More specificity and targeted mechanism of action CHEMOTHERAPY Effects and Pharmacokinetics Most effective on rapidly dividing cells Narrow margin between therapeutic effects and toxicity Many adverse effects Combinations of drugs are usually more effective Resistance to drugs can develop Dosing varies Depends on type of cancer, prior treatment, and administered drugs Body surface area (m2) often used in calculating dose CHEMOTHERAPY Adverse effects (Dose-limiting) Describes side effects of a drug or other treatment that are serious enough to prevent an increase in dose or level of that treatment. Drugs also target normal health rapidly dividing cells, and many adverse effects relate the effects on these cells: Bone marrow- neutropenia (nadir), thrombocytopenia, anemia Hair follicles – hair loss GI tract cells- diarrhea, mucositis, N & V (emetic potential) Teratogenic- risks vs benefits in pregnancy Infertility IV forms- risk of extravasation CHEMOTHERAPY – Cell Cycle Specific Drugs that are cytotoxic during a specific phase of the cell cycle Often used for solid tumours and circulating tumours Cell cycle specific do not work in the resting or dormant phase of the cycle Classes 1. Antimetabolites 2. Mitotic inhibitors 3. Topoisomerase inhibitors 4. Antineoplastic enzymes CHEMOTHERAPY – Cell Cycle Specific CHEMOTHERAPY – Antimetabolites Antimetabolites Analogue that is structurally similar to a normal cellular metabolite Mechanism of Action Inhibit cellular growth by interfering with the synthesis or actions of several components needed for cell reproduction (metabolic pathways) Two mechanisms 1. Falsely substitute purines, pyrimidines and folic acid 2. Inhibit crucial enzymes involved in the synthesis of purines, pyrimidines and folic acid Results in inhibition of synthesis of RNA, DNA and proteins needed for cellular survival Cell-cycle phase target: S phase (DNA synthesis) CHEMOTHERAPY – Antimetabolites Antimetabolites 3 subclasses based on which component is inhibited: 1. Folate Antagonists 2. Purine Antagonists 3. Pyrimidine Antagonists Indications for use Solid tumours Some hematological cancers Used in combination with other drugs to enhance cytotoxic effects Many drug interactions Mostly given IV, PO available for some CHEMOTHERAPY – Antimetabolites Folate Antimetabolites Methotrexate Pemetrexed Raltitrexed (Tomudex®) Mechanism of Action Inhibits enzyme needed to activate folic acid into its active form (folate) which is needed for DNA synthesis Result- DNA is not synthesized and cell dies CHEMOTHERAPY – Antimetabolites Folate Antimetabolites Indications for use Methotrexate - solid tumours of head, neck, breast, lung CA, leukemias & lymphomas Pemetrexed- only for lung Cancer Raltitrexed- colorectal cancer, also makes more radiation-sensitive Administration Weekly administration, IV, PO Methotrexate High doses cause severe bone marrow depression Usually given with rescue drug- Leucovorin (an antidote for folic acid antagonists) Also used in severe rheumatoid arthritis and psoriasis due to its immunosuppressive activity CHEMOTHERAPY – Antimetabolites Purine Antimetabolites Cladribine Fludarabine (F-AMP) Mercaptopurine (6-MP) Thioguanine (6-TG) Mechanism of Action Act as synthetic forms of adenine and guanine (purine bases needed for DNA/RNA) and interrupts synthesis of both RNA and DNA Indication for use Leukemia Lymphoma CHEMOTHERAPY – Antimetabolites Pyrimidine Antagonists Capecitabine Cytarabine (ara-C) Fluorouracil (5-FU) Gemcitabine Mechanism of Action Acts as synthetic form of cystine and thymine (for DNA); uracil and cytosine (for RNA) Incorporate themselves into the metabolic pathway for DNA and RNA synthesis, disrupting RNA/DNA production Administration Only available IV (except capecitabine- PO) CHEMOTHERAPY – Antimetabolites Adverse Effects N&V, diarrhea Hair loss Adverse Events Bone marrow suppression Methotrexate may induce pneumonitis and liver damage Can cross BBB causing neuronal damage Peripheral neuropathy CHEMOTHERAPY – Mitotic Inhibitors Mitotic Inhibitors Plant-derived compounds Targets various phases of the cell-cycle occurring Start or before (G2) or during mitosis (M) Therapeutic effect is that it will slows cell division Indications for use Variety of solid tumours Some hematological cancers Synergistic use to enhance cytotoxic effects of other drugs CHEMOTHERAPY – Mitotic Inhibitors 2 Subclasses with variation in MOA 1. Vinca Alkaloids 2. Taxanes Vinca Alkaloids Vinblastine Vincristine Vinorelbine MOA Derived from periwinkle and mandrake plants Interferes with mitotic spindle structures during M phase Inhibits cell reproduction & causes cell death CHEMOTHERAPY – Mitotic Inhibitors Vincristine is very neurotoxic but still used because it lacks bone marrow suppression in comparison to other drugs Taxanes Paclitaxel Docetaxel MOA Derived from bark of yew trees Acts on late G2 phase and M phase Administration Paclitaxel high risk adverse effects during infusion highly trained nurse needed to administer CHEMOTHERAPY – Miotic Inhibitors Adverse Effects Hair loss Nausea, vomiting Adverse Events Bone marrow depression Nephrotoxic Hepatotoxic High risk of extravasation Antidote is Hyaluronidase SC to site Warm compresses CHEMOTHERAPY – Topoisomerase Inhibitors 2 Subgroups of Topoisomerase Inhibitors 1. Topoisomerase II Inhibitors 2. Topoisomerase I Inhibitors Topoisomerase II Inhibitors Etoposide Teniposide MOA Inhibit enzyme topoisomerase II which breaks DNA stands Targets late S phase and G2 phase of cell cycle Indicated for use in Testicular Cancer CHEMOTHERAPY – Topoisomerase Inhibitors Topoisomerase I Inhibitors Topotecan Irinotecan Newer class of chemo drugs Semi-synthetic drug derived from a Chinese shrub (camptotheca) Mechanism of Action Binds to the DNA-topoisomerase I complex during the S phase Inhibits proper DNA functioning by slowing and breaking DNA strands CHEMOTHERAPY – Topoisomerase Inhibitors Topoisomerase I Inhibitors Indications for use Ovarian cancer Colorectal cancer Small cell lung cancer Administration Injectable only CHEMOTHERAPY – Topoisomerase Inhibitors Adverse Effects Stomatitis Hair loss GI Upset (mild) Irinotecan can cause indirect cholinergic effects 2-10 days post infusion Anticholinesterase activity = cholinergic effects Severe diarrhea Lacrimation Sweating Adverse Events Bone marrow depression Cardiovascular toxicity ▪ Pulmonary embolism ▪ Cerebral Vascular Accident ▪ Myocardial Infraction CHEMOTHERAPY – Topoisomerase Inhibitors Special notes Etoposide Specific Adverse Event Contains diluent that may cause hypotension When used in testicular cancer has a risk of orthostatic hypotension CHEMOTHERAPY – Antineoplastic Enzymes Antineoplastic Enzymes Pegasparagase Asparaginase (Kidrolase, Erwinase) Drugs synthesized from the cultures of certain bacteria (e. Coli) using recombinant DNA technology Mechanism of Action These enzymes make cells unable to synthesize asparagine Asparagine is required during G1 for DNA synthesis and cell survival Indications for Use Lymphocytic leukemia only CHEMOTHERAPY – Antineoplastic Enzymes Antineoplastic Enzymes Administration Injectable only Specific Adverse Events Allergic reactions to Pegasparagase are common Impaired pancreatic function Hyperglycemia Pancreatitis CHEMOTHERAPY – Cell Cycle NON-Specific Cell Cycle Non-Specific Drugs that are cytotoxic to neoplasms at any phase of the cell cycle 2 broad Categories Alkylating drugs Cytotoxic antibiotics Chemotherapeutic agents emerged in the 1940s. The first drug was an alkylating drug developed from mustard gas (a warfare agent) which was known as nitrogen mustard CHEMOTHERAPY – Cell Cycle NON-Specific Alkylating drugs Mechanism of Action Alkylation = A chemical process by which an alkyl group is transferred from one molecule to another in DNA This leads to abnormal chemical bonds between strands of DNA Cellular DNA is now defective (DNA damage) Prevents reproduction and causes cell death These drugs vary in the number of alkylation reactions they can cause CHEMOTHERAPY – Cell Cycle NON-Specific Alkylating drugs Indication for Use Used to treat a wide variety of solid and circulating cancers 3 categories of Alkylating drugs 1. Classic alkylators (nitrogen mustards): 2. Nitrosoureas 3. Miscellaneous alkylators CHEMOTHERAPY – Cell Cycle NON-Specific Alkylating drugs Classic alkylators Cyclophosphamide Chlorambucil Isofamide Melphalan Nitrosoureas Carmustine Lomustine Streptozocin CHEMOTHERAPY – Cell Cycle NON-Specific Alkylating drugs Miscellaneous alkylators Busulfan Carboplatin Cisplatin Dacarbizinem Oxaplatin Procarbaine hydrochloride Temozolimide CHEMOTHERAPY – Cell Cycle NON-Specific Alkylating Drugs Adverse Events Similar dose limiting effects as cell-cycle specific drugs Nephrotoxicity, neurotoxicity (carboplatin, cisplatin) Bone marrow suppression (espec. Cyclophosphamide) Ototoxicity (cisplatin) Pulmonary fibrosis (busulfan) IV extravasation risk → antidote Sodium Bicarbonate IV and SC to site Some drug interactions (i.e. caution with other drugs with nephrotoxic effects) CHEMOTHERAPY – Cell Cycle NON-Specific Cytotoxic Antibiotics Natural and semi-synthetic substances derived from mould (Streptomyces) Mechanism of Action “Intercalation” = Inserts molecule between two strands of DNA to block DNA synthesis Inhibit Topoisomerase II enzyme which breaks DNA strand Many also generate free radicals which also causes DNA strand breaks and programmed cell death Indications for use Solid tumours Hematological cancers CHEMOTHERAPY – Cell Cycle NON-Specific Cytotoxic Antibiotics Anthracyclines Daunorubicin Doxorubicin Epirubicin Idarubicin Valrubicin Other cytotoxic antibiotics Bleomycin (cell cycle specific) Dactinomycin Mitomycin Mitoxantrone Administration by Injection only Danunorubicin, Dactinomycin should be given via central line, not peripheral IV CHEMOTHERAPY – Cell Cycle NON-Specific Adverse Effects Hair loss N&V Adverse Events Bone suppression is most common adverse effect Hepatotoxicity Bleomycin can cause pulmonary toxicity (pulmonary fibrosis and pneumonitis) Daunorubicin & Doxorubicin = Heart failure and cardiomyopathy Many drug interactions (espec. Digoxin) HORMONAL HORMONAL Antineoplastics Not considered a chemotherapy Sex hormones accelerate t he growth of certain cancers (i.e. breast) Mechanism of Action Block body’s sex hormone receptors OR Administer hormones with opposing effects (i.e. Male vs female hormones) HORMONAL Antineoplastics Therapeutic use in Breast Cancer The growth of some types of breast cancer cells is modulated by estrogen (increases growth) “Estrogen receptor-positive breast cancer” Blocking the production or utilization of estrogen will slow growth Estrogen Receptor positive tumour drugs Tamoxifen (Nolvadex-D) Toremifene (Fareston) HORMONAL Antineoplastics Selective estrogen receptor modulators Anastrozole Exemestane Letrozole Anti-estrogen effects on breast tissue, may be proestrogenic in uterine tissue Prevent formation of Aromatase or inhibit its action (required for synthesis of estrogen) NOT used with Tamoxifen HORMONAL Antineoplastics Prostate Cancer Prostate cancer can be modulated by testosterone (increase growth) Hormones that interfere with testosterone production or compete with androgen receptors Androgen Deprivation Therapy Bicalutamide (Casodex) Flutamide (Eulexin) Emcyt (Estramustine) HORMONAL Antineoplastics Adverse Effects/Events Female Specific Menopause-like symptoms Hot flashes Night sweats Irregular periods Osteoporosis Increased risk of endometrial cancer (tamoxifen) General Fatigue Infertility and Impotence (men) Blood clots CV risk (increased cholesterol) TARGETED DRUG THERAPY TARGET DRUG THERAPY Major focus of cancer drug research Uses drugs to recognize specific molecules involved in growth of cancer cells while sparing normal healthy cells Imatinib (tyrosine inhibitor) Vorinostat (histone deactelyase inhibitor) TARGET DRUG THERAPY Immunotherapy Natural or artificial substances that mimic or block natural cell responses to kill, control or change the behaviour (growth) of cancer cells Use the body’s immune system against the cancer Hematopoietic or Colony Stimulating Factors agents can increase immunity affected by chemotherapy Monoclonal Antibodies (MABs) Angiogenesis Inhibitors- Inhibit growth of new blood supply to tumors TARGET DRUG THERAPY Immunotherapy Interferons and Interleukin-2 Are types of cytokines May improve immune system action against cancer cells Stimulates the growth and activity of certain immune cells that recognize and destroy cancer cells Immunostimulants Monoclonal Antibodies (MABs) trigger the immune system to attack/kill cancer cells Inhibits proliferation of cancer cells by blocking growth signals May be used to carry cancer drugs or radiation to cancer cells (radioimmunotherapy) TARGET DRUG THERAPY CAR-T Cells Harvesting of patients own T-cells and biologically modifying them in lab Involves taking a patient's own WBC immune cells(T-cells) Then reprogramming them to attack tumors Reprogramed T-Cells are re-infused into patient T-Cells attack and destroy all cancer cells they have been programed to recognized Rapidly becoming the standard of treatment for patients with Leukemia that has relapsed. New trials are being done to see if effective for some solid tumors SUPPORTIVE DRUGS SUPPORTIVE DRUGS Used to offset the damaging effects of cancer treatment Chemo-protective Radio-protective Cyto-protective ▪ Supportive drugs are NOT chemotherapy drugs ▪ They help to protect cells or organs from the side effects of chemotherapy drugs or radiation therapy SUPPORTIVE DRUGS Drug Protects Mechanism of Action Allopurinol(Zyloprim) Kidneys Joint Prevents the buildup of uric acid that can occur in treatment of lymphoma or leukemia Rasburicase(Fasturtec) Kidneys, joints, heart, nervous Helps clear uric acid from the blood system & Prevention of Tumor Lysis Syndrome Dexrazoxane(Zinecard) Heart May prevent damage from doxorubicin (Adriamycin) Folinic acid (leucovorin) Blood, GI tract Protects from damage that may occur from methotrexate. Colony-stimulating factors Bone Marrow, Immune system Lowers risk of low blood counts by Filgrastim (Neupogen, Grastofil) stimulating the bone marrow to increase the production of blood cells Tumor Lysis Syndrome – during treatment cancer cells break down faster than the kidneys can remove the biproducts. This leads to toxic levels of uric acid, potassium, phosphate and low calcium General Patient Education Understanding of treatment protocol, adverse effects etc. Report signs of infection, bleeding, anemia Anticipate hair loss Frequent mouth care Avoid others with infections Diarrhea management Increase fluid to 3L/day Avoid ASA, ibuprofen- bleeding risk Reproductive counselling prior to treatment, contraception Canadian Cancer Society as a resource Nursing Considerations Establish therapeutic relationship and offer support Labs before and during treatment Electrolytes, minerals, uric acid levels, CBC, platelets, bleeding times, liver and renal function Always check neutrophil count and signs of infections Neutropenia is a common adverse event and can be life threatening in the presence of an infection (Febrile Neutropenia) Tumour markers may be used to monitor effectiveness of treatment Monitor: Oral mucosa, swallowing, weight, nutritional status, bowel patterns, N & V Signs of infection, bleeding, anemia Antiemetics for N & V 30- 60 min before treatment &/or meals Nursing Considerations Be alert to look alike- sound alike naming (i.e. “vincas”, rubicins”) Safe handling of drugs Training and certification, PPE Special spill kits Monitor IV site carefully Extravasation protocols Patency of central lines Double flush bodily secretions Observe reverse isolation protocols if required Canadian Association of Nurses in Oncology as a resource
