Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
All you need to know about Chemotherapy. Lynne Cormode What is Chemotherapy? Systemic treatment against malignant cells to try and prevent growth, invasion, metastasis and eventual death of patients. Initially discovered after WW1 when soldiers exposed to nitrogen mustard were observed to have had a improvement in solid tumour size. Chemotherapy Intent / Terms Adjuvant To reduce cancer load thereby improving symptoms and prognosis Radical To down stage tumour prior to surgery or radical treatment Palliative To reduce cancer recurrence Neo-Adjuvant Curative treatment Concomitant Combined modality treatment (Chemo/radiotherapy) Regime Cycle Single / Combination Drugs Varies from weekly to 12 weekly Dose Body surface area i.e. mg/m2 (Dubois + Dubois) Renal excretion i.e. AUC (Area under the curve) Chemotherapy Forms / Types Oral Intravenous Locally Bolus / Infusional Central / Peripheral Intratheccal Intraperitoneal / Intravesical Topical Intra-arterial (limb perfusion) Subcutaneous or Intramuscular Classic chemotherapy Immunotherapy Biological / Molecular targeted therapy Modes of Action - General Inhibition of cell multiplication via Macromolecular synthesis and function i.e. DNA / RNA / Proteins Cytoplasmic signalling Cell membrane receptor synthesis, expression and function Cellular environment The Cell Cycle Interphase G1 (presysnthesis gap) S (synthesis of DNA) G2 (postsynthesis gap) Mitosis M (cell division) Prophase Metaphase Microtubles align chromosomes Centromeres halfway between spindle poles Anaphase Sister chromatids condense Mitotic spindle assembles Nuclear envelope breaks down Separation of sister chromatids at centromere moving towards poles Cytokinesis (cell division) starts Telophase Nuclear membranes reforms Chromosomes become extended Cytokinesis completes Traditional Chemotherapy Classes ANTIMETABOLITES TAXANES PODOFYLOTOXINS ANTIMICROTUBULE AGENTS CHEMOTHERAPY VINCA ALKALOIDS ANTITUMOUR ANTIBIOTICS ANTRACYCLINES CAMPTOTHECINES ALKYLATING AGENTS NITROSOUREAS PLATINUM DRUGS Antimetabolites nucleoside analogues / antagonists FOLIC ACID Methotrexate inhibits DHFR PURINES Guanine Adenine TETRAHYDROFOLIC ACID PYRIMIDINES Cytosine Thymine Uracil 5FU Capecitabine Cytarabine Mercaptopurine Azathioprine Fludarabine NUCLEOTIDES DNA REPLICATION inhibit Thymidylate synthase Antitumour Antibiotics Topoisomerases are essential enzymes that maintain the topology of DNA. Inhibtion interferes with both transcription and replication of DNA by upsetting proper DNA supercoiling. Cell cycle specfic – G1 and S phase Type I topoisomerase inhibitors, Camptothecins (Irinotecan, Topotecan) Type II topoisomerase inhibitors, Epipodopyllinotoxins (Etoposide); Antracyclines (Doxorubicin, Daunorubicin) – also induce O2 free radicals that break DNA strands inhibiting replication Others include Actinomycin D, Mitomycin C, Bleomycin Antimicrotubule Agents Prevent microtubule function therefore preventing the separation of chromatids. Cell cycle dependant – M (anaphase) Taxanes (Paclitaxel; Docetaxel) – causes hyperstabilisation of microtubules Vinca Alkaloids (Vincristine, Vinblastine, Vinorelbine) – inhibits the assembly of tubulin into microtubules Alkylating agents Ability to alkylate many nucleophilic function groups causing the formation of covalent bonds (cross linking of DNA) Non cell cycle specific Platinum drugs (Oxaliplatin, Cisplatin, Carboplatin) – renally excreted Nitroureas (Carmustine, Lomustine, Semustine) – highly lipid soluble i.e. cross BBB Others Cyclophosphamide, Dacarbazine, Procarbazine, Melphalan, Busulphan, Chlorambucil. Hormones / Cytokines Prednisolone / Dexamethasone Tamoxifen Aromatase Inhibitors (Letrozole, Anastrozole) Gonadotropin releasing hormone agonists (Zoladex) Interferon alpha Monoclonal Antibodies Designed to target highly expressed tumour specific antigens thereby increasing the immune response to the tumour cell. Rituximab (CD20) Cetuximab (Epidermal Growth Factor Receptor 1) Transtuzumab (Human Epidermal growth factor Receptor 2) Bevacizumab (Vascular Endothelial Growth Factor) Tyrosine Kinase Inhibitors Imatinib (Philadelphia chromosome, Bcr-Abl TKI) Erlotinib (EGFR inhibitor) Sunitinib (multiple receptor inhibitors inc VEGFR, PDGFR) Chemotherapy Toxicities 1 Bone Marrow Suppression Skin / Hair Neutropenia Anaemia Thrombocytopenia GI Nausea / Vomiting Mucositis Reproductive Palmar plantar erythodysthesia Sun sensitivity Extravasation Rashes Alopecia (scalp cooling) Nephrotoxicity Hepatic toxicity Chemotherapy Toxicities 2 Neurotoxicity Cardiac toxicity Peripheral neuropathy Ototoxicity Constipation Coronary vasospasm Reduced LVEF Bladder toxicity Haemorrhagic cystitis Practical Issues Ward admissions Neutropenic sepsis Symptomatic myelosupression Dehydration Cardiac events Extravasations Anaphylactoid reactions Chemotherapy spillage policy