Cancer Chemotherapy

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Summary of Dr. Chand's Cancer Chemotherapy lecture
jmburk07
Flashcards by jmburk07, updated more than 1 year ago
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Created by jmburk07 over 9 years ago
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Chemotherapy Uses 1) Advanced Disease: No other tx possible. Chemo alone. Metastatic disease. Improve QOL. 2) Localized disease: Chemo + radiation. Neo-Adjuvant therpay. Other tx available but not totally effective. Anal, bladder, esophagea, laryngeal Ca 3) Adjuvent therapy: Surgery + radiation. REduce systemic and local effects and imrpove patient survival. Breast, Lung, Colon, Gastric, Wilm's tumor, Astrocytoma
Primary Resistance No response with drug therapy indicates towards a primary resistance (Malignant melanoma, renal cell cancer, and brain cancers). as been blamed on loss of p53 Tumor suppressor gene
Acquired Resistance In response to exposure of chemotherapeutic agent. Usually a multidrug resistance occurs. Increased expression of MDR1 gene in certain tumors
Classes of Anticancer Drugs Alkylating AGents Antimetabolites Natural Anticancer drugs Anticancer Abx Misc. Anticancer Drugs
Alkylating Agents Examples Chlorambucil, Melphalan, Cyclophosphamide, Busulphan, Thiotepa, Cisplatin, Dacarbazine
Antimetabolites Examples Methotrexate, 5 fluroacil, Cytarabine, Fludarabine
Natural Anticancer Drugs Examples Vinblastine, Vincristine, Epipodophyllotoxins
Anticancer Antibiotics Examples Anthracyclines, Mitomycin Bleomycin
Misc. Anticancer Drugs Examples Imatinib, Niclotinib, Cetuximab
Alkylating Agents MOA Transfer their Alkyl groups to DNA w/in the nucleus causing cell death. React chemically w/ sulfhydryl, amino, hydroxyl, and phosphate groups 2ndary Mechanism: Carbamoylation of lysine proteins thus inhibiting protein chains and DNA strand breakage
Alkylating Agents Adverse Effects Dose related. Bone marrow, GIT, and reproductive system affected most d/t rapid cell division N/V are severe Injection abscess and induration Carcinogenic
Cyclophosphamide [Clinical applications & Toxicity] Clinical Applications: Inactive drug acted upon by CYP450 breast, ovarian, non hodgkins, CLL, Wilm's tumor, Neuroblastoma Toxicity: Hemorrhagic cystitis, BM depression, leukopenia
Chlorambucil [Clinical Applications & Toxicity] Clinical Application: CLL, NHL Toxicity: N/V
Melphalan [Clinical Applications & Toxicity] Clinical Applicaitons: MM, Breast, Ovarian Ca Toxicity: N/V
Busulphan [Clinical Applications & Toxicity] Clinical Applicaitons: CML Toxicity: Skin pigmentation, pulmonary fibrosis, adrenal insufficiency
Carmustine/Lomustine [Clinical Applications & Toxicity] Clinical Applications: Brain Cancer Toxicity: N/V, myelosuppression
Dacarbazine/Procarbazine [Clinical Applications & Toxicity] Clinical Applications: Hodgkins & NHL Toxity: Myelosuppression
Cisplatin/Carboplatin [Clinical Applications & Toxicity] Clinical Applications: Small cell and non small cell lung, breast, bladder, Head, and neck cancer Toxicity: Nephrotoxicity, Ototoxicity
Methotrexate [MOA] Folic Acid Analog Binds to DHFR (Dihydrofolate Reductase) Inhibits production of THFR Inhibits formation of cellular proteins needed by Cancer cells to grow and proliferate
Methotrexate [Delivery] Oral, IV, intrathecal Oral erratic absorption Renal excretion: Penicillin, ASA, cephalosporins, and NSAIDs inhibit renal excretion of methotrexate, cause toxicity
Methotrexate [Clinical Applications & Toxicity] Clinical Application: Breast, head and neck, osteogenic sarcoma, NHL, Bladder Ca Toxicity: Mucositis, myelosuppression, neutropenia
5-Flurouracil [Clinical Applications & Toxicity] Clinical Applications: Colorectal, anal, breast, head and neck, hepatocellular Toxicity: Nausea, mucositis, diarrhea, neurotoxicity
Fludarabine [Clinical Applications & Toxicity] Clinical Applications: NHL Toxicity: Immunosuppresion, fever, myalgia, arthralgia
6-Mercaptopurine [Clinical Applications & Toxicity] Clinical Application: AML Toxicity: Myelosuppression, Hepatotoxicity
Cytarabine [Clinical Applications & Toxicity] Clinical Applications: ALL, AML, CLL, blast crisis Toxicity: N/V/D, Myelosuppression, Neutropenia
Gemcitabine [Clinical Applications & Toxicity] Clinical Applications: pancreatic, bladder, breast, ovarian Toxicity: N/V/D, myelosuppression
Natural Anticancer Drugs [Examples] Vinblastine, Vincristine, Vinorelbine Paclitaxel Daunorubicin, Doxorubicin Etoposite, Podophyllotoxin Bleomycin Mitomyin
Vinblastine, Vincristine, Vinorelbine (Vinca rosea-Periwinkle) [MOA, Clinical Applications & Toxicity] -MOA-Inhibition of Tubulin, loss of mitotic spindle -Clinical Applications: HL/NHL, Breast, Kaposie's, Wilms, ALL -Toxicity: N/V, Myelosuppression, Mucositis, SIADH, Neurotoxicity, Paralytic ileus
Paclitaxel [Clinical Applications & Toxicity] -Clinical Applications: Breast, non small cell, Ovarian, Prostate, Bladder -Toxicity: Myelosuppression, Peripheral Neuropathy
Daunorubicin/Doxorubicin [Clinical Applications & Toxicity] -MOA: Oxygen free radicals bind to DNA causing breaks -Clinical Applications: Breast, Hodgkin's, AML, ALL, Thyroid, Wilms -Toxicity: Cardiotoxicity, Red Urine, Myelosuppression
Etoposide Podophyllotoxin [MOA, Clinical Applications, & Toxicity] -MOA: Inhibits Topoisomerase -Clinical Applications: Lung, Hodgkins, Gastric Ca -Toxicity: Alopecia, Myelosuppression
Bleomycin [Clinical Applications & Toxicity] -Clinical Applications: HL, NHL -Toxicity: Alopecia, Skin toxicity
Mitomycin [Clinical Applications & Toxicity] -Clinical Applications: Bladder, gastric, breast -Toxicity: Myelosuppression, Hemolytic-Uremic syndrome
Imatinib, Nilotinib Inhibitors of tyrosine kinase and prevent phosphorylation of the cell kinase substrates by ATP.
Nilotinib Second generation 50x more potent than imatinib
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