Drugs Used in Oncology Past Paper (CPH1902 2024) PDF

CPH1902 13th November 2024 Drugs Used in Oncology Chemotherapy The main classes in Chemotherapy are: 1. Alkylating agents 2. Plant derivatives 3. Topoisomerase inhibitors 4. Antitumor antibiotics...

CPH1902 13th November 2024 Drugs Used in Oncology Chemotherapy The main classes in Chemotherapy are: 1. Alkylating agents 2. Plant derivatives 3. Topoisomerase inhibitors 4. Antitumor antibiotics 5. Antimetabolites 6. Miscellaneous antineoplastics A PanDa TalkIng ANTI AMerican MAyPoles Alkylating Agents Overarching drugs Most active in the resting phase of the cell Cell-cycle non-specific - damage DNA Classes of Alkylating drugs: My Nice Aunt Paints Every House and Tree Mustard gas derivatives Cyclophosphamide Chlorambucil Melphalan Ifosfamide Cycling Chloride Metals Ireland Nitrosoureas Carmustine Lomustine Streptozocin Car Licence Strip Alkyl sulfonates Busulfan Platinum Carboplatin (most commonly used) Cisplatin Oxaliplatin -platin = platinum Ethylenimines Thiotepa Hexamethylmelamine Theo Hexose Hydrazines & Triazines Altretamine Procarbazine Decarbazine Temozolomide A PRO DECorator: TEMu 1  CPH1902 13th November 2024 Plant Derivatives Derived from certain types of plants Some have been synthesised artificially nowadays Cell cycle specific → attack the cells during various phases of division Types of Plant Derivatives Vince’s Tax Payers Camped Vinca Alkaloids Vincristine Vinblastine Vinorelbine These are also known as antimicrotubule agents Taxanes Paclitaxel Docetaxel Podophyllotoxins Etoposide teniposide These are also known as Topoisomerase Camptothecin analogs Irinotecan inhibitors topotecan Topoisomerase Inhibitors Inhibit the action of topoisomerase enzymes Divided into 2 classes: ○ Topoisomerase 1 inhibitors ○ Topoisomerase 2 inhibitors Topoisomerase 1 Inhibitors Irinotecan topotecan Topoisomerase 2 Inhibitors Amsacrine Etoposide Etoposide phosphate Teniposide Mitoxantrone 2  CPH1902 13th November 2024 Antitumor Antibiotics Made from natural products produced by the species of the soil fungus Streptomyces Cell-cycle specific - act during multiple phases of the cell cycle Types of Antitumor Antibiotics Ants Can’t Mingle Anthracyclines Doxorubicin Idarubicin Epirubicin Daunorubicin D.I.E.D Chromomycin Dactinomycin Plicamycin Miscellaneous Mitomycin Drugs which do not fit in either class - Still Bleomycin produced by the same fungus. Antimetabolites These drugs are very similar to normal substances within the cell Cell-cycle specific - attack cells at very specific phases in the cycle Types of Antimetabolites Flies Push-Pull Ants Folic Acid Antagonists Methotrexate Pemetrexed PM Pyrimidine Antagonist 5-Fluorouracil Floxuridine Cytarabine Capecitabine Gemcitabine Flounder Flies Cycling Casper Ghost Purine Antagonist 6-mercaptopurine 6-thioguanine Adenosine deaminase Cladribine inhibitor Fludarabine Nelarabine Pentostatin Click, Flack, Nick, Pack 3  CPH1902 13th November 2024 Miscellaneous Antineoplastics Ribonucleotide reductase inhibitor Hydroxyurea Adrenocortical steroid inhibitor Mitotane Enzymes Asparaginase Pegaspargase Antimicrotubule agent Estramustine Retinoids Bexarotene Isotretinoin Tretinoin (ATRA) Targeted Therapy Target the cancer’s specific genes Proteins Tissue environment Which contribute to cancer growth and survival They therefore do not damage the good side effects. Classes of Targeted Therapy MAry ThinKIng AnD Assisting MalTese Monoclonal antibodies Trastuzumab Bevacizumab Cetuximab Rituximab Tyrosine kinase inhibitors Imatinib Apoptosis-inducing drugs Bortezomib Angiogenesis inhibitors Bevacizumab Sunitinib Thalidomide mTOR inhibitors Everolimus Main side-effects: skin problems (photosensitivity, rash, dry skin, itching, red sore cuticles, hand-foot syndrome), hypertension, bleeding, poor wound healing Hormone Therapy Stop the production of a specific hormone Block hormone receptors or substitute chemically similar agents for the active hormone, which cannot be used by the tumour cell These depend on the type of cancer 4  CPH1902 13th November 2024 Types of hormone therapy drugs: Addison And Andrew Anti Aroma Established London Pro Serm Adrenal Steroid Inhibitors Aminoglutethimide Mitotane Androgens Fluoxymesterone Testosterone Testolactone Antiandrogens Bicalutamide Flutamide Nilutamide Antiestrogens Tamoxifen Toremifene Aromatase Inhibitors Anastrozole Exemestane Letrozole Estrogens DES(diethylstilbestrol) Estradiol (estrace) Premarin Luteinizing hormone-releasing hormone (LHRL) Goserelin acetate Agonists Progestational Agent Medroxyprogesterone acetate Selective Estrogen Receptor Modulators (SERMs) Raloxifene Cytotoxic Adverse Effects Associated with individual drugs and specific chemotherapy regimens Many adverse effects of cytotoxic drugs often do not occur at the time of administration, but days or weeks later Common adverse effects: ○ Extravasation (leaking) of intravenous drugs ○ Oral mucositis ○ Nausea and vomiting ○ Alopecia ○ Thromboembolism ○ Bone-marrow suppression Cytotoxic drugs may be contraindicated in patients with acute infection, any infection should be treated before, or when starting, cytotoxic drugs Fever in a neutropenic patient, meaning they have too low white count, needs immediate broad spectrum antibacterial therapy. In selected patients, the duration and severity of neutropenia can be reduced by the use of recombinant human granulocyte-colony stimulating factors 5  CPH1902 13th November 2024 Cytotoxic Drug Dosing Most anticancer agents have a steep dose response relationship and a narrow therapeutic index Small variations in the administered dose can lead to severe and life-threatening toxicity in some individuals, and under-dosing in others, which can compromise the cancer outcomes. Doses of cytotoxic drugs are determined using a variety of different methods, including: ○ Mg of drug per m2 BSA (height and weight of patient needed) ○ Algorithms for calculating body surface area Dubois and Dubois Mosteller For targeted therapies, fixed dose regardless of weight of BSA, or fixed dose or on a mg/kg basis Area under the curve-based dosing is applicable for drugs which are cleared through glomerular filtration, like carboplatin, because there is a strong correlation between carboplatin clearance and creatinine clearance. Dose modification is based on multiple factors and is drug specific ○ Hematological toxicity - dose modification depends on white blood count, neutrophils or platelets ○ Renal impairment - dose is adjusted based on creatinine clearance ○ Hepatic impairment - dose is adjusted based on bilirubin level and other LFTs at times ○ Other toxicities depending on the grade: stomatitis, diarrhea, palmar/plantar erythema (PPE) ○ History of previous adverse effects to the cytotoxic drug ○ Doses may also differ depending on whether the drug was given alone or in combination Complications of Immunotherapy Skin toxicity Colitis Hepatitis Endocrinopathies: Thyroid Diabetes Hypophysitis (Inflammation of the anterior lobe of the pituitary gland) Pneumonitis Nephritis Neurological (including polyneuropathy, facial nerve palsy, myasthenia gravis, Guillain Barré syndrome, encephalitis and aseptic meningitis) Other – cardiac, mild or moderate myalgia and/or arthralgia, ocular 6