Anti Cancer Agents

8/7/2019 Anti Cancer Agents

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Anticancer Drugs


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Anticancer Drugs

In the US, cancer is the 2nd cause of death (heart dx -1st)Results from the alterations in DNA w/in the cell

Use of anticancer drugs include - cure, control, palliativeChemo may be used as sole Rx of Ca or in conjunction w/radiation & surgeryCell-Cycle Nonspecific & Specific - Anticancer drugs cause

Ca cell death by interfering w/ Ca cell replication- Interferes w/ either all phases or a specific phase of thecell cycle (pg. 575, fig. VII-I)


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Anticancer Drugs

- Cell-cycle nonspecific (CCNS) = act on any phase duringthe cell cycle

- kill the cell during the dividing & resting phase of cell

cycle: alkylating drugs, antitumor antibiotics, hormones- Cell-cycle specific (CCS) = act on a specific phase of thecell cycle

- effective against rapidly growing Ca cells:antimetabolites, vica alkaloids, antitumor antibioticsGrowth fraction & doubling time are two factors thatplay a major role in the Ca cell response to the anticancerdrug


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Anticancer Drugs

- Anticancer drugs are more effective against the Ca cellshaving a high growth fraction - leukemias & somelymphomas

- Ca of the breast & colon & melanomas = low growthfraction = poor response to antineoplastics

- small & early forming Ca cells & fast-growing tumorsrespond well to anticancer drugs

Drug Rx for early dx = higher cure rate than late stagesSolid tumors = low growth fraction = less sensitive todrugs


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Anticancer DrugsHigher doses of drugs result in better tumoricidal (killing)effectsCa growth usually faster in earlier stages. As tumor grows

bld supply dec & growth rate dec. = drugs more effectiveagainst sm. tumors w/ sufficient bld supplyCancer Chemotherapy - tumor cells are similar to normalcells in that it is difficult for antiCa drugs to be selective in

killing tumor cells & not normal cells- Drug protocol = therapy too long & doses too high = toxic- Eliminating every Ca cell = difficult (1 mill. cells couldremain w/o symptoms - ??? on continuing Ca therapy


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Anticancer Drugs

Drug Resistance - tumor resistance can develop against anantiCa drug d/t drug used infrequently or the tumor slocation limits the effectiveness

- Brain tumors respond poorly (BBB)Combination Chemotherapy - Single-agent drug therapyseldom used

- Combo of drugs to enhance tumoricidal effects

- CCS & CCNS are often combined to max. cell deaths- dec. drug resistance, shorten & intensify drug effect- inc. destruction of Ca cells, dec. drug toxicity - severaldrugs = lower doses = less injury to normal cells


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Anticancer Drugs

Alkylating Drugs - one of the largest groups of Cadrugs

- Kill cells by forming cross-links on DNA strands- Belong to the CCNS category & affect all phases of

the cell cycle - effective against many types of cancers: acute & chronic leukemias, lymphomas,mult. myeloma, solid tumors (breast, ovaries, uterus,lungs)

- Classified into 4 groups: Nitrogen mustards(Cyclophosphamide), nitrosoureas (Carmustine),

alkyl sulfonates (Busulfan), alkylating-like drugs


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Anticancer Drugs

Cyclophosphamide (Cytoxan) - Nitrogen mustard- Action - Inhibition of protein synthesis through

interference w/ DNA replication by alkylation of DNA- Use - Hodgkin s dx, solid tumors- SE - bone marrow suppression , alopecia, N & V,

diarrhea, wt. loss, hematuria (maintain adequate

hydration), impotence, sterility- An early antiCa drugs, can be administered PO


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Anticancer Drugs

Antimetabolites - Oldest group- Resemble natural metabolites - disrupt the metabolic

processes & some of the agents inhibit enzymesynthesis

- CCS (5-FU, floxuridine - also CCNS)- Subdivided into folic acid (folate) antagonists

(Methotrexate) - also used as an immunosuppressantfollowing organ transplant - substitutes for folic acid,needed for the synthesis of proteins & DNA;pyrimidine analogues (5-fluorouracil); purine

analogues (6-mercaptopurine)


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Anticancer Drugs

F lurouracil (Adrucil, 5- FU , Efudex) - IV- Action - CCS, blocks the enzyme action necessary forDNA & RNA synthesis- low therapeutic index- alone or w/ other drugs, can cross BBB

- Use - Ca of breast, cervix, colon, ovary, stomach,

pancreas- SE - N, V, diarrhea, alopecia, rash, bone marrow

suppression, stomatitis (inflammation of oralmucosa)


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Anticancer Drugs

Antitumor Antibiotics - (Bleomycin, dactinomycin,daunorubicin, doxorubicin) - inhibit protein & RNAsynthesis & bind DNA causing fragmentation

- Classified as CCNS (except for bleomycin)- Drugs differ from each other & are used for diff. Ca s

D oxorubicin (Adriamycin) - IV

- Action - Inhibits DNA & RNA synthesis- Use - W/ other agents for Ca of breast, ovaries, lung,

bladder, leukemias, lymphomas- SE - Similar to general adverse rxns to antineoplastics


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Anticancer Drugs

- Capable of causing vesication - blistering of tissue if drug leaks out into surrounding interstitial tissue -rxn ranges from painful, reddened swelling to deep

necrotic lesion needing debridement & skin grafts- Drug is a deep red color - urine will be red 1 - 2 days

after administration- Can cause cardiotoxicity

Mitotic Inhibitors (Vinca Alkaloids) - block celldivision at M phase of cell cycle (Vincristine,Vinblastine, Vinorelbine tartrate) - CCS


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Anticancer Drugs- Single drugs or in combo therapy- SE - leukopenia, alopecia, stomatitis, N,V, neurotoxicityHormones & Hormone Antagonisits - Used in combo

therapy for Rx of various Ca.- 2 major actions: 1) Agonists that inhibit tumor cell growth

- estrogen, progestins, androgens, adrenocorticosteroids& 2) Antagonists that compete w/ endogenous hormone -aminoglutethimide, tamoxifenCorticosteroids (glucocorticoids) classified asantiinflammatory agents - suppressing the inflammatory

process that occurs w/ tissue involvement


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Anticancer Drugs

- Hormones also suppress leukicytes & is effective incontrolling leukemia & lymphoma

- Used w/ other drugs as part of an antineoplasticregimen - MOPP (oncovin, procarbazine &prednisone) - Hodgkin s disease

- Prednisone frequently prescribed - inexpensivecortisone derivative

- Dexamethasone & hydrocortisone - IM or IV - candecrease cerebral edema caused by a brain tumor


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Anticancer Drugs

Tamoxifen (Nolvadex) -- Action - exact neoplastic action unknown, acts as anestrogen antagonist

- Use - Breast cancer in women and men- SE - Adverse rxn s usually minor & well toleratedMiscellaneous Agents - antineoplastic drugs whose

MOA does not place them in a category. Used incombo w/ other Ca drugs to Rx a variety of solidtumors & hematologic malignancies - pactitaxel(Taxol), docetaxel ( Taxotere), pentostatin (Nipent),

etoposide (VP-16)


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Anti Cancer Agents