Chemotherapy jslum.

com | Medicine
Alkylating Agent (CCNS) Antimetabolites (CCS) Plant Alkaloids (CCS) Cytotoxic Antibiotics (CCNS) Hormones & Antagonists Platinum (CCNS) Interferons
MOA Maximal cytotoxic effects in S-phase Act on M-Phase of cell cycle (except Mainly CCNS except Bleomycin Hormone-sensitive derived MOA Responsible for Protective Def ense
Intercalating (Synthesis) Etoposide – G2 & late S-Phases) (CCS – G2 Phase) tumours → Hormone Dependant Intercalating against Pathogens, Tumour
(Form Covalent Bonds between DNA Folate Antagonist Vinca Alkaloids Interact with DNA – Disruption of Inhibit DNA synthesis
bases)(particularly 2 Guanine G-G) MTX (Methrotrexate) Vincristine (VX), Vinblastine (VB), DNA function Hormone Antagonists can inhibit Form Intra-, Inter- strand crosslinks 3 subtypes – α, β, γ
• DNA unwinding Pyrimidine Analogues Vinorelbine(semi-synthetic) Act as Radiomimetics growth of tumours with DNA molecules
• Impair synthesis 5-FU Tax anes (Simultaneous use avoided) Cisplatin Produced by Recombinant DNA
• Abnormal base-pairing Ara-C Paclitaxel, Docetaxel (Radiation recall effect) Cell must have Intracellular Carboplatin
• Intra- & Inter- strand links with Purine Analogues Podophyllotoxins Dactinomycin recepto rs specific to Hormone Oxaliplatin Interferon α (2a, 2b)
DNA molecule (Defective 6-MP Etoposide Anthracyclines (useful in CA chemotherapy)
Replication, DNA strand break) 6-TG Doxorubicin, Daunorubicin
Bleomycin
Toxic Effects Toxic Effects (Methotrexate) Vinca Alkaloids (IV) Anthracyclines (IV) Glucocorticoids Cisplatin (IV) Interferons (INF) (IM, IV, Subcut)
BM suppression BM depression MOA 3 MOA Prednisone Therapeutic uses MOA
GIT disturbance Damage GI, Skin Epithelium Bind to Tubulin Intercalate DNA Inhibitory effects on lymphocyte Testicular CA (PVB) (Exact mechanism not understood)
Impair gametogenesis Nephrotoxicity Prevent Spindle formation (Inhibit Nucleic acid synthesis) proliferation Ovarian CA
Acute non-lymphocytic leukaemia (Spindle poisons) (DNA fragmentation) (+ cyclophosphamide or 5-FU) Direct Antiproliferative effec t
(mutagenic) Arrest at Metaphase (Inhibit DNA repair) Therapeutic uses Bladder CA (alone)
Nitrogen Nitrosoureas Methotrexate (MTX) Hyperuricaemia due to (Inhibit Topoisomerase II) Lymphomas Toxic Effects Immunomodulary effects
mustards Carmustine MOA Rapid Cytotoxic effects Bind to cell membrane Myelomas Severe Nausea, Vomiting (on NK cells, T-cells, B-cells,
Cyclophosphamide Lomustine Compete with Folic Acid (FA) for active Cell destruction (Alter membrane function, Ion ALL (induce remission) (Antiemetics mandatory) Macrophages)
Ifosfomide Others site of dihydrofolate reductase (DHFR) (Treat with Allopurinol) transport) Hodgkin’s (MOPP) Nephrotoxicity
Melphalan Busulphan Prevent DNA, RNA, Protein Synthesis Metabolised in Liver (CYP450) Generate Free Radical Non-Hodgkin’s (CHOP) (Adequate Hydration, Diuresis – Induction of Tumour cell Antigens
Mechlorethamine Thiotepa Cell Death Excreted in Bile, Faeces (Single strand break in DNA) Manitol, Slow infusion)
Chlorambucil Dacarbazine Therapeutic uses Excreted in Bile Ototoxicity (30%) Differentiating effec ts
Cyclophosphamide (Oral, IV) Dose/ Administration/ Uses Vinblastine Vincristine (Need Dose ↓ in Liver disease) Sex Hormones HypoMg/ HypoCa (on cell tumours)
Prodrug – Inactive until metabolized by LDMTX (Oral) – Anti-inflammatory, (Oncovin) Therapeutic uses Estrogens Peripheral Neuropathy
CYP450 in Liver Immunosuppressants, RA, severe Psoriasis Hodgkin’s Paeds Leukemia Doxorubicin Daunorubicin Diethylstilbestrol, Ethinyloestradiol Therapeutic use
Drug crosses BBB (ABVD) (combine with (Adriamycin) Prostate CA Carboplatin Hair cell Leukaemia
IDMTX (IV) & HDMTX (IV) – Malignancy,
Metabolites appear in urine Prednisone) Solid Tumor Hematologic Breast CA Derived from Cisplatin Early stag e CML
ALL, Lymphoma, Choriocarcinoma
Therapeutic uses (curative), Solid Tumours (Breast, H&N) Testicular CA Adult lymphoma (Sarcoma, CA (Acute ↓ Toxic effects than Cisplatin T-Cell Lymphomas
Antitumor & Immunosuppression (PVB) Breast - CAF) Leukaemia) Progestogens (↓ Nausea, Vomiting, Nephro,
Intrathecal – Prev ent relapse (Hidden Solid Tumours Hematologic Not useful in Ototoxicity) Toxic Effects
CLL Medroxyprogesterone, Meges trol
Malignant cells in BBB, Eyes, Testes) (Breast, Lung) CA (Acute Adult Solid ↑ Myelosuppressive effects Flu-like symptoms
Lymphoma Endometrial CA
Solid Tumours (Breast, Lung, Hodgkin’s Leukaemia, Tumor Renal CA Myalgias
Drug Resistance (due to) (MOPP) Hodgkin’s - Headache
Ovary, Childhood neoplasm)
↓ Drug Transport Non-Hodgkin’s ABVD) Cisplatin + Carboplatin
Non-Hodgkin’s (CHOP) GnRH Analogues
Altered DHFR with ↓ Affinity for MTX (CHOP) Toxic Effects Reproductive organ CA
Breast (CMF) Goserelin, Buserelin
↓ Polyglutamate formation Cardiotoxicity
Toxic Effects Toxic Effects Advanced Breast CA
↑ Synthesis DHFR Extravasation – Tissue Necrosis
Active metabolite = Acrolein Vinblastine Vincristine Prostate CA
(Oncovin) BM Depression
Bladder toxicity (Haemorrhagic cystitis) Excrete unchanged by Kidney
• Ensure good Hydration, N- BM suppression Mild BM Red Urine (warn patients)
Avoid in renal impairment Hormone Antagonists
acetylcystein, Mesna (protect suppression
Bleomycins (IV, IM, Intracavi tary) Anti-Estrogens (Tamoxifen)
urinary tract – form non-toxic Leucovorin (Folinic acid) (= Rescue drug) Mild Significant Block binding of estrogens to
MOA
compound) Neurotoxicity Neurotoxicity
(Revers e DHFR Inhibition) Bind to DNA recepto rs of estrogen-sensitive
Given in accidental Overdosage Paraesthesia cancer cells
Cause Strand Breaks
Rescue Normal cells (BM, GIT) while Constipation Inhibit Synthesis Breast CA
tumour cells on ↑ Dose MTX (effects) Paralytic Ileus G2 Phase (most effective) Progestin-resistant
Carmustine (IV), Lomustine (Oral) 5-FU (5-Fluorouracil) Cellulitis (if extravasated), Nausea Therapeutic use endometrial CA
Cross BBB (↑ Lipid soluble) MOA & Vomiting, Alopecia, SIADH Testicular CA (PVB)
Treat Brain CA (primarily) Inhibit formation of Thymidine Lymphomas Anti-Androgens (Flutamide)
(essential for DNA synthesis) Paclitaxel (IV), Docetaxel (Oral) (Non-Hodgkin’s - ABVD) Prostate CA
Toxic Effects MOA Squamous cell CA
BM Suppression (most marked) Therapeutic uses Spindle poison Toxic Effects
Renal toxicity Solid Tumours (Colon CA) Prevent Microtubulin Disassembly Anaphylactoid reaction
Topical agent for Skin Cancers Microtubules – Overly stable Fever, Chills
↑ Effectiv eness Chromosome cannot Desegregate Pulmonary Fibrosis
(used with Leucovorin) Therapeutic uses (Bleomycin lung)
↑ Response rates Parlitaxel Docetaxel Mucocutaneous Manifestations
(used in Combination) ↓ Potent ↑ Potent (eg. Palms)
(5FU + Cisplatin – Ovary, H&N CA) Ovarian, Breast CA
Breast (CMF) BM Suppression
Neutropenia = Dose limiting Toxicity