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Anticancer Agents
1st packet
124
Pharmacology
Graduate
12/08/2012

Additional Pharmacology Flashcards

 


 

Cards

Term
All neoplastic cells have 3 common characteristics
Definition

-Persistent proliferation

-Invasive growth

-Formation of metastases

Term
bcl-2
Definition
cell death suppressor-apoptosis pathway
Term
Tummor suppressor genes
Definition

-p53 gene is present in a high number of human cancers

-mutated from tumor supressor gene to an oncogene

-Many onther suppressor genes

-p21

 

Term
Metastasis
Definition
“secondary tumors”
• Invasions of unaffected organs
• They appear at other locations in the body
– Distant to the primary site
– Migration via lymphatic or circulatory systems.
Term
Types of anticancer drugs
Definition

• Cytotoxic drugs
• Hormonal Receptor Antagonists
• Biological response modifiers (BRM)
– Immunostimulants
– Immunosuppression
• Vaccines
Term
Cytotoxic Drugs
Definition

• Chemotherapeutics drugs
• Anticancer drugs


• Many different chemicals, with a variety of
mechanisms and site of action within the cell
– They inhibits cell division

Term
Anticancer drugs rely on the rapid rate of growth
and division of cancer cells to provide a degree of
selectivity.
Definition
• Suppress all proliferating cells
– Thus normal rapidly dividing cells are affected!
• Bone marrow; Oral & GI lining; hair follicles; lymphoid
organs.
Term
Cytotoxic drugs.
Definition
• DNA Alkylating Agents
• DNA Intercalating Drugs (Antitumor Antibiotics)
• Mitotic Inhibitors (Plant alkaloids)
• Topoisomerase inhibitors
• DNA synthesis inhibitors
– Folate Antagonists (Antimetabolite)
– Purine Antagonists
– Pyrimidine Antagonists
– Ribonucleotide reductase Inhibitors
Term
The cell cycle
Definition
Term

 

 

The cell cycle
• Has 4 major phases: G1; S; G2; M

Definition
– G1 : post mitotic, cell prepares to make DNA
– S: DNA synthesis occurs
– G2: post mitotic; DNA synthesis completed; cell
prepares for mitosis
– M: mitosis occurs resulting in 2 daughter cells.
• They can either enter G1 or G0 (resting).
Term
Phase specific Drugs
Definition

– G1 : Interferon


– S: DNA synthesis inhibitors: Fluorouracil; Methotrexate;
Cytarabine; Fludarabine, Mercaptopurine; Thioguanine


– G2: Bleomycin,Etoposide,Teniposide


– M: Mitotic inhibitors: vincristine

Term
Non-Phase specific drugs
Definition

All DNA alkylating
drugs and most DNA
intercalating agents

 

Antitumor antibiotics

Term
Growth Rate
Definition

• Solid tumors:
        – Initial growth rate is rapid.


• Growth rate decreases as tumor size increases.

       – Surgery and radiation therapy decreases tumor
burden promotes remaining cells to enter the
proliferative phase.


• Growth rate may increase following angiogenesis

Term
• Concept of Log Kill
Definition
– First-order kinetics. That a given dose of
anticancer agents, kills a constant fraction of
tumor cells.
– that is, the magnitude of tumor cell kill by
anticancer drugs is a logarithmic function.
– Estimate the number of drug courses required to
99% of cells.
• In theory we require 3 to 4 drug courses to eliminate
99% cancer cells.
Term
– Different cancer have different sensitivity to
chemotherapeutic agents.
Definition

• Lymphomas and leukemia: most responsive to
treatment


• Colorectal cancer, lung squamous cell carcinoma are
least responsive to treatment

Term
Pulse treatment
Definition
• Treatment every 3-4 weeks
• Allows for maximum effect with complete
• hematologic + immunologic recovery
between courses
• Decrease adverse effects
• The therapeutic effect not diminished
Term
_______: resistant to most anticancer drugs
Definition
Melanoma
Term
Drug Resistance
Definition
Increased inactivation of drug
– Alkylating agents: cisplatin
– Antimetabolites
– Bleomycin
Reduced activation of drug
– anti-metabolites which must be converted to the
nucleotide before they are active
Term
Drug Resistance
Definition
• Enhanced cell repair
– Cells in G0
                  -Alkylating agents
Decreased affinity of target enzyme or
receptor for drug.
– Antimetabolites: Methotrexate
Term
Drug Resistance

Definition

Reduce drug uptake
– Methotrexate
Increase drug efflux
– P-glycoprotein, a pump confer multi drug
resistance.
– Resistance cells have a greater number of
P-glycoprotein

Term
– P-glycoprotein can be block by Calcium channel
blockers:
Definition
nifedipine; verapamil
Term
Multiple Drug Resistance
Definition
– Cells exposed to a single drug develop
resistance to a broad range of cytotoxic agents

– Breast Cancer Resistant Protein (BCRP)
– Multiple drug Resistant Protein (MRP)
Term
– Majority of tumors develop MDR through over
expression of ______
Definition
the drug efflux pump (P-glycoprotein;
MDR1).
Term
Common Drug Toxicity

Definition
• Stimulation of the chemoreceptor trigger
zone in the medulla
– Nausea & vomiting
• mild to severe, depends on agent
• Cisplatin & carmustine are the worst
• Effects minimize with antiemetic agents
• Serotonin antagonists: ondansetron
• Neuroleptics: droperidol
• Corticosteroids: dexamethasone
• Central Dopamine antagonist: metoclopramide
Term
Myelosuppression results in
Definition
– Leukopenia
– delayed onset, clearing of existing circulating
cells
– Predisposes patient to infection
– Recovery can be enhanced with recombinant
forms of hematopoietic growth factors
• Epoetin alfa; filgastrin; sargramostim
– Thrombocytopenia
– Anemia
Term
Organ specific toxicity
Definition
• Depend on individual agent
– Example:
Doxorubicin (anthracyclines) – cardiotoxicity
Cisplatin - renal toxicity
Bleomycin - pulmonary fibrosis
Term
Minimizing toxicity
• Agents developed to prevent or minimize organ
toxicity
Definition

Dexrazoxane prevent doxorubicin induced
cardiotoxicity
– Administration of mannitol and sodium thiosulfate
prevent cisplatin induced renal toxicity.
   • Mannitol maintain renal blood flow & tubular function
  • Sodium thiosulfate inactivates the drug in the kidney.

Folinic acid (leucovorin) counteracts methotrexate
induced megalobastic anemia.
– Human granulocyte colony-stimulating factor partially
reverse neutropenia associated with cancer treatment.

Term
DNA Alkylating Agents
Definition

Nitrogen mustards
Cyclophosphamide; Ifosfamide
Chlorambucil; Mechlorethamine; Melphalan
Nitrosureas
Carmustine; lomustine
Platinum compounds
Cisplatin, Carboplatin, Oxaliplatin
Others:
– Busulfan; Mitomycin; Dacarbazine

Term
DNA Alkylating Agents
Definition

• Non Phase Specific agents
• Highly reactive agents. Interacts (cross-link) with
DNA strands
      • Radical formations, Covalent bonds
– Monofunctional agents
• Alkylating agents binding to one site
– result in miscoding of DNA
– Bifunctional agents
• Alkylating agents binding to two sites, cross-linkage of
DNA strains; especially injurious
– Result- inhibition of DNA replication, often cell
death

Term
DNA Alkylating Agents
Definition

• Resistance
 – Production of enzymes that repair DNA
 – Decrease uptake of drug
 – Increase production of glutathiones
• Toxicity: Very toxic to dividing cells
  – Bone marrow; hair follicles, GI & germinal
epithelium
  – Blood dycrasia (neutropenia; thrombocytopenia,
anemia)

Term
Clyclophosphamide
Definition

DNA Alkylating Agent

   -Nitrogen mustards
         – Cyclophosphamide

 

• Prodrug require metabolic activation (Cyto P450)
• Widely used
– Chronic lymphocytic leukemia; breast & ovarian cancer;
etc
• Potent immunosuppressant
Rheumatoid arthritis & autoimmune nephritis
• Adverse effects
– Alopecia; nausea & vomiting; myelosuppression;
hemorrhagic cystits
– Cardiac dysfunction; altered ADH secretion

Term
Cisplatin; Carboplatin;
Oxaliplatin
• has efficacy against a wide range of neoplasma
Definition

– IV as 1st line for testicular, ovarian and bladder cancer
– Main agent in cancer drug cocktails (including H&N
cancers)
– Useful for treatment of melanoma

Term
Cisplatin; Carboplatin;
Oxaliplatin
Definition

• Adverse effects
– GI distress, Alopecia; myelosuppression
– Severe nausea & vomiting and renal toxicity
– Neurotoxic and hematoxicity
– Oxaliplatin: parathesia of the hand, feet, perioral
area, jaw tightness, larynopharyngeal dysesthesia

Term
Antimetabolites (DNA synthesis
Inhibitors)
Definition

– Folate Analogs/Antagonists
       • Methotrexate; trimetrexate
       • Premetrexed disodium
– Purine Antagonists
       • Mercaptopurine; thioguanine
– Pyrimidine Antagonists
       • Fluorouracil; Cytarabine
– Ribonucleotide reductase Inhibitors
       • Hydroxyurea

Term
– Folate Analogs/Antagonists

Definition

Methotrexate; trimetrexate
• Premetrexed disodium

Term
– Purine Antagonists

Definition

Mercaptopurine; thioguanine

Term
– Pyrimidine Antagonists

Definition

Fluorouracil; Cytarabine

Term
– Ribonucleotide reductase Inhibitors
Definition

Hydroxyurea

Term
Methotrexate
Definition

– Folic acid analog
• Actively transported into cells
– Mechanism of action
• Substrate for and inhibitor of dihydrofolate
reductase
• i.e. inhibit production of tetrahydrofolic acid
(FH4),leading to a decrease synthesis of
thymidylate, purine nucleotides, and amino
acids……. interferes with nucleic acid and protein
synthesis.
S phase specific

Term
Methotrexate [Folex]
– Pharmacokinetics
Definition

• Given orally or parenterally
• Do not penetrate the CNS
       – For treating CNS conditions, need to be injected
intrathecally
• Not metabolized, clearance is dependent on renal function.
       – Required adequate hydration to prevent crystallization

Term
Methotrexate (folex)– Clinical Uses

Definition

• Acute leukemias, non-Hodgkin’s lymphoma; breast cancer,cutaneous T cell lymphoma, etc


• Rheumatoid arthritis; lupus erythematosus; abortifacient

Term
Methotrexate [Folex]
– Adverse Effects & Toxicity
Definition
• Bone marrow depression; pulmonary infiltrates &
fibrosis; oral (mucositis) and GI ulcerations
• Long term use leads to hepatotoxicity; pulmonary
infiltrates and fibrosis.
• Adverse effects can be minimized by administration of
folinic acid (Leucovorin); to bypass the metabolic
block
This is called “leucovorin rescue”

Term
• The following drugs increase the toxicity of
methotrexate:

Definition
– NSAIDs, sulfonamides, sulfonyureas
Term
______ is an
Antidote to Methotrexate
Definition

Leucovorin

 

 

• “Leucovorin Rescue”
– Leucovorin, given to patients to bypass the
metabolic block
– Usually when methotrexate is given a high dose
(toxic dose)

Term

Pemetrexed disodium (Alimta®)

(Folate Analogs/Antagonists)
• Mechanism:

Definition

– Disrupts multiple enzyme targets
• thymidylate synthase (TS), dihydrofolate reductase
(DHFR), glycinamide ribonucleotide formyltransferase
(GARFT), and aminoimidazole carboxamide
ribonucleotide formyltransferase (AICARFT), the
enzymes involved in folate metabolism and DNA
synthesis, resulting in inhibition of purine and
thymidine nucleotide and protein synthesis

Term
Purine Analogues _____, _____, and _____
Definition

Mercaptopurine and Thioguanine
• Affect the incorporation of purine derivatives into
nucleic acids. The analogues interferes with the
conversionof inosinic acid to nucleotides of adenine
and guanine, resulting in the inhibition of DNA and
RNA synthesis.
Fludarabine
• Analogue of adenosine, inhibits ribonuclleotide
reductase and DNA polymerase, resulting in the
inhibition of DNA synthesis

Term
Mercaptopurine (Purinthol)
Definition
• Prodrug - Required metabolic activation
• Active drug disrupt several biochemical purine
pathways
– Converted to a nucleotide by enzyme HGPRT
• (hypoxanthine-guanine phosphoribosyltransferase)
– Mutation confer resistance
S phase specific
Term
Mercaptopurine (Purinthol) Uses, Toxicity, and DI
Definition


Uses
• Acute & chronic lymphocytic leukemia.
Toxicity
• Mild myelosuppression, bone marrow suppression
Drug interaction with
• Allopurinol, reduce dose of mercaptopurine

Term
Pyrimidine Anatagonists
Definition

Cytarabine
– Cytosine arabinoside or ara-C
5-Fluorouracil

Term
Fluorouracil (5-FU) (Adrucil)
Definition

• Analogue of thymine
• Prodrug: Required metabolic activation.
– 5-FU: Two active metabolites
           • 5-FdUMP - inhibits thymidylate synthases
            [thymine synthesis - a major building block for
            DNA synthesis]. “ Thymineless death”
           • 5-FdUTP is incoorporated into RNA by RNA
            polymerase and interferes with RNA function

Term
Fluorouracil (Adrucil)
• Clinical uses
Definition
– Breast; bladder, colorectal, gastric, colon,
ovarian and head & neck squamous cell
carcinoma

Term

Fluorouracil (Adrucil)

• Toxicity:

Definition
Bone marrow depression; GI distress& oral
ulcerations; hair loss; neurological deficits.
Term
Hydroxyurea
Definition

Ribonucleotide reductase Inhibitors

 

– Interfere with synthesis of DNA, during the S
phase of cell division, without interfering with
RNA synthesis
– Inhibits ribonucleoside diphosphate reductase,
preventing conversion of ribonucleotides to
deoxyribonucleotides
– Cell-cycle specific for the S phase and may hold
other cells in the G1 phase of the cell cycle

Term
Antitumor Antibiotics
Definition

• Anthracyclines
– These are DNA Intercalating Drugs
        • Daunorubicin; Doxorubicin; Idarubicin (semi-synthetic)
        • Mitoxantrone
– Others
Bleomycin;
• Dactinomycin

Term
Antitumor Antibiotics

• Mechanism
Definition

NON PHASE SPECIFIC

 

• Intercalation of DNA
– Cause deformation and uncoiling of DNA
• Inhibition of topoisomerase II
– Resulting in strain breakage
• Formation of free radicals
– Reactive hydroxyl radicals causing DNA cleavage

Term
Antitumor Antibiotics
• Daunorubicin; Doxorubicin; Idarubicin
Definition
– Indications
• Acute nonlymphocytic leukemia; Hodgkin’s disease;
bladder cancer, ovarian cancer gastric carcinoma etc
– Mechanism of Action
• They intercalate between base pairs, inhibiting
topoisomerase II and generate free radicals
• They block the synthesis of RNA and DNA and
cause DNA strand breakage
Term
Daunorubicin; Doxorubicin;Idarubicin
– Adverse effects
Definition
Cardiotoxicity; bone marrow depression, GI
distress, nausea & vomiting; severe alopecia;
mucosal alterations.

Term

• Daunorubicin; Doxorubicin;Idarubicin

– Drug Interactions

Definition
• Toxicity increased by cyclosporine;
cyclophosphamide and mercaptopurine
Verapamil: increases toxicity by inhibition of Pglycoprotein
Term
Bleomycin
Definition

Antitumor Antibiotic

 

– Mixture of two glyco peptides obtained from
Streptomyces verticillis.
– greatest effect on cells in G2 phase, Phase specific

Term

Bleomycin

Mechanism

Definition

– Mechanism
• General free radicals, which binds to DNA, cause
strand break and inhibit DNA synthesis.
• and intercalation with DNA

Term

Bleomycin

 

 

Definition

• Hodgkin’s and non- Hodgkin’s lymphomas,
testicular cancer and other solid tumors, squamous
cell caricinomas
Term
Bleomycin
– Adverse effects
Definition

• Serious: pulmonary and mucocutaneous toxicities
      – Develop pneumonitis that progresses to interstitial
fibrosis, hypoxia and death
    » Monitor patient for cough, dyspnea, pulmonary infiltrates

 

– Mucocutaneous: oral stomatitis; skin
pigmentation, erythema and edema

 

Term
Mitotic Inhibitors (Plant alkaloids)
Definition

Vinca Alkaloids
    – Vincristine; Vinblastine
    – Vinorelbine is a semisyntehtic derivative of
vincristine
Taxanes (bark of the western Pacific Yew
tree)
    – Paclitaxel
    – Docetaxel

Term
Mitotic Inhibitors
• Vinca Alkaloids
Vinblastine [Alkaban; Velsar]; Vincristine[Oncovin];
Etoposide [VePesid]
Definition

– Acts on the M phase
    • Prevents cell division
    • Blocks mitosis by disrupting the assembly of
microtubules, the filaments that move chromosomes

 

– Toxicity

    • GI distress, alopecia, bone marrow depression,
neurotoxic

Term

Vinca Alkaloids

– Adverse effects

Definition
• Dose dependent peripheral neuropathy
• Suppress tendon reflexes
• Paresthesias is common
Term

Mitotic Inhibitors


• Taxanes


Paclitaxel [Taxol]; Docetaxel [Taxotere]
– Mechanism

Definition

• Late G2
– promote formation of stable microtubule bundle,
thereby inhibiting cell division


• M phase
– disrupting the assembly of microtubules,
inhibiting mitosis

Term
• DNA Topoisomerase
Definition
– Enzymes that maintain the normal structural
topology of DNA
– They produce strain breakage, permiting strands
to pass through gap before the breaks are reseal
Topoisomerase I: breaks and reseal singlestranded
DNA
Topoisomerase II: breaks and reseal doublestranded
DNA
Term
– Topoisomerase I inhibitors
Definition

• Alkaloid from Camptotheca acuminata
• Irinotecan; Topotecan

Term
• Topotecan (Hycamin); Irinotecan
Definition

– Inhibit topoisomerase I enzymes
• Prevents repair of DNA stands, impairs
DNA replication; G2 phase

 

– Toxicity:
• Bone marrow depression; alopecia; peripheral
neuropathy; mucositis
• Nausea, vomiting, diarrhea

Term
• Etoposide (Etopophos); Teniposide
Definition

– Inhibit topoisomerase II enzymes
• Prevents resealing of DNA stands
• G2 phase


– Toxicity:
• Bone marrow depression; alopecia; peripheral
neuropathy; mucositis
• Nausea, vomiting, diarrhea

Term
• Etoposide (Etopophos)
– Indications:
Definition
• Most hematologic cancers and solid tumors especially
testicular carcinoma; lung cancer; non-Hodgkin’s
lymphoma
• Is used as a preoperative treatment for bone marrow
transplantation
• Has synergistic activity when combine with cisplatin
Term
Estrogen & Androgen receptor
antagonists
Definition
– Tamoxifen; Flutamide
Term
Gonadotrophin-releasing Hormone
agoinsts
Definition
– Leuprolide; Goseretin
Term
Aromatase Inhibitors
Definition
– Aminoglutethimide; Anastrozole
Term
Steroid Hormones
Definition
• Prednisolone
– Corticosteroids
– Use in combination with other antineoplastic
drugs in acute and chronic lymphocytic
leukemia, Hodgkin’s disease, lymphoma and
multiple myeloma.
• Estrogen
– Treatment of advance prostate carcinoma and
post menopausal breast cancers
Term
The six least toxic groups of anticancer drugs
Definition
Glucocorticoids; Androgens &
antiandrogens; Estrogens & Antiestrogens;
Aromatase Inhibitors; Progestins;
Gonadotrophin-releasing hormone analogs
Term
Glucocorticoids: Prednisone
is employed in
following types of cancer
Definition
– lymphomas associated with Cushing syndrome.
– inducing remission in patients with acute
lymphocytic leukemia
– Combined with other cancer drugs in the
treatment of Hodgkin and non-Hodgkin
lymphomas.
Term
Glucocorticoids: Prednisone
Definition

• Prednisone is an inactive prodrug
– Metabolized to prednisolone …….. binds to the
intracellular receptor.


– Drug-receptor complex enters the nucleus É
binds to chromatin, activating the transcription of
specific genes …… protein synthesis of proteins.
affinity.

Term
Esterogen is used in the treatment of  ____ and ___
Definition

Advance prostate carcinoma

Post Menopausal breast cancers

Term
Estrogen Receptor Antagonist
• Indicated for breast cancer cells which recognize
estrogen for growth stimulation.
Definition

Drug Class: SERM (Selective estrogen
receptor modulator)

 

Blocks estrogen receptors
       • Tamoxifen (Nolvadex; Soltamox); toremifene
(Fareston); raloxifene
       • Indicated for breast cancer that is estrogen dependent.

Term
Tamoxifen (Nolvadex)
• Can stimulate or block estrogen receptors -
depends on tissue
Definition
• Blocks estrogen receptors in breast cancer
– Prevents the natural hormone (estradiol) from binding
with the receptor.
– Prevents stimulation of growth & proliferation.
• Modulates varies signaling pathways
– Ceramide, NFκB, Capases
Term
Aromatase Inhibitors
Definition
• Examples:
– Aminoglutethimide; Anastrozole; Letrozole; Exemestane
Term
Aromatase reaction:
Definition
Responsible for the extra-adrenal synthesis of
estrogen from androstenedione in liver, fat, muscle, skin
and breast tissue.
– Important source of estrogen in post menopausal
women
– Inhibition decrease the production of estrogen.
Term
Aminoglutethimide (Cytadren)
Definition

-Aromatase inhibitor

– Inhibits both adrenal and extra-adrenal synthesis of
estrone and estradiol
– Fat tissue is major source estrogen
– It also inhibits hydrocortisone synthesis .. leading a
compensatory increases in adrenocorticotropic hormne
(ACTH) to overwhelm the blockage of the adrenal.
Hydrocortisone is coadministered to prevent
symptoms of adrenal insufficiency.

Term
• Aminoglutethimide (Cytadren)
– Adverse effects
Definition
• Fatigue, nausea
• Skin rash, adrenal insufficiency, myelosuppression
Term
Aromatase Inhibitors
• Anastrozole (Arimidex); Letrozole (Femara)
Definition
– Non steroidal selective inhibitor, more selective
and potent than Aminoglutethimide,
– do not require hydrocortisone supplementation.
– has no effects on adrenal glucocorticoid or
mineralocorticoid synthesis
– do not predispose to endometrial cancer
– Devoid of androgenic side-effects
Term
• Exemestane (Aromasin)
Definition
• Aromatase Inibitor
– Steroidal irreversible inhibitor
Term
• Synthetic non-steroidal antiandrogens
– Blocks androgen receptors
Definition


Flutamide (Eulexin), nilutamide (Nilandron)
bicalutamide (Casodex)


– Indicated for prostate cancer that is androgen
dependent.

Term
Flutamide (Eulexin)
Definition
– Metabolized to an active drug
– Competitively blocks receptor
• Prevents translocation into the nucleus. Therefore blocks the effects of testosterone on gonadotropin secretion.
• Use in combination with leuprolide.
Term
Flutamide Adverse effects and DI
Definition

– Adverse effects:
• Gynecomastia, hot flashes, breast tenderness, galactorrhea,
impotence, libido decreased, tumor flare; GI distress

 

– Drug Interaction:
• Warfarin, compete with plasma protein binding sites

Term
The Antiandrogen ______ is Similar to Flutamide, higher incidence of visual
problems
Definition
Nilutamide (Nilandron)
Term
The Antiandrogen _____ is similar to Flutamide, higher incidence of liver
failure.
Definition
Bicalutamide (Casodex)
Term

_________, primary stimulus
for the secretion of testosterone by the testis

 

 ________,
stimulate the secretion of estrogen.

Definition

Leuteinizing hormone (LH)

Follicle stimulating hormone (FSH)

Term
Leuprolide and goserelin
Definition

– Synthetic peptide analogs GnRH

 

– Agonists, binding with the GnRH receptor in the
pituitary, desensitizing the receptor …….
inhibiting release of FSH and LH
• BOTH androgen and estrogen production are
suppressed.
– Adverse effects
• Hot flushes, impotence, gynecomastia.

Term
Gonodotrophin-releasing hormone
Definition

• Diethylstilbestrol, leuprolide (leuprorelin)


– Suppress luteinizing hormone from the pituitary
gland, thereby suppress testosterone production
– Estrogen also act directly to suppress prostate
cancer proliferation

Term
Thalidomide
Definition
– Antiangiogensis
– immune modulation
• Inhibit tumor necrosis factor production, stimulate T
cell proliferation, increase interferon and interleukin-2
release
Term
Monoclonal Antibodies
• Examples:
Definition

Trastuzumab; Rituximab; Bevacizumab;
Cetuximab; Daclizumab; Palivizumab;
Gemtuzumab; I131-tositumomab,
Muromonab,

 

 

– mab: monoclonal antibodies
– xi: chimeric antibodies
– Muro: murine antibodies

Term
• Trastuzumab
Definition
– Metastatic breast cancer with over-expression of
HER-2 (Membrane human epidermal growth
factor receptor protein 2)
– Targets the extracellular domain of the HER2
growth factor receptor
• Blocks the tyrosine kinase leading to the inhibition of
cell proliferations in breast cancer tissue with
overexpressed HER2 protein
• Problem … tyrosine kinase mediates over 50 cell
growth signaling and interplay with other pathways!
Term
Rituximab
Definition
– Monoclonal antibody directed against CD20 antigen on
the surfaces of B lymphocytes (normal & malignant)
– CD20 antigen is expressed on all B-cell non-Hodgkin
lymphomas but not in other bone marrow cells.
– following slow infusion, Rituximab results in the rapid
depletion of both normal and malignantB cells.
– Fab domain binds to CD20 antigen of B lymphocytes
and the Fc domain recruits immune effector functions
(complement , antibody-dependent, cell mediated
cytotoxicity of the B cells).
Term
Trastuzumab


Definition
– Binds to HER2 receptor and leads to
• down regulation of HER-2 receptor expression
• induction of antibody-dependent cytotoxicity
• decrease in angiogenesis
Term
Trastuzumab
– Adverse effects

Definition
• Congestive heart failure
– worse when combined with anthracycline
– Use with caution in patients with underline cardiac dysfunction
• Infusion-related chills, headache, dizziness, nausea,
vomiting
Term
Rituximab
– Adverse Effects
Definition
• Hypotension, bronchospasm, angioedema
• Chill, fever, cardiac arrhythmias,
• Tumor lysis syndrome: within 24 hours of first dose. Acute renal
failure, hyperkalemia, hypocalcemia, hyperphosphatasemia
• Leukopenia, thrombocytopenia and neutropenia.
Term
Bevacizumab  [Avastin]
Definition
– Anti-angiogenesis agent, binds to and stops/prevents
vascular endothelial growth factor (VEGF) from
stimulating new blood vessel formation.
– First line drug against metastatic colorectal cancer.
– Co-administered with 5-FU, irinotecan and oxaliplatin
Term

Bevacizumab  [Avastin]

Adverse effects

Definition
Adverse effects:
– Hypertension, TIA, stoke, angina and MI
– ONJ; stomatitis, GI perforations, diarrhea
– Delayed wound healing
– Proteinuria
Term
Cetuximab [Avastin]
Definition
– Binds to epidermal growth factor receptor (EGFR) on
surface of cancer cells inhibiting tumor cell growth by
• decreasing tyrosine kinase activity, matrix
metalloproteinase activity, growth factor production.
• Increasing apoptosis
• Angiogenesis inhibitor
– Indicated for colorectal cancer, where it is coadministered
with irinotecan
Term

Cetuximab [Avastin]

– Adverse effects:

Definition

• Hypotension, stomatitis, ONJ, rash, fever,
constipation
Term
Angiogenesis Inhibitors
Definition
• Agents that prevents the development of blood
supply to tumors.
– no blood supply
• No nutrients,
• No away of eliminating toxic metabolites
• Result is limited or no growth
Term
Angiogenesis Inhibitors
• Mechanisms:
Definition

– Target endothelial cell functions
– Vascular endothelial growth factors receptors (VEGFRs)
– Monoclonal antibodies vascular endothelial growth
factors (VEGFs)

Term
Drugs that target endothelial cell proliferations
Definition
– Thalidomide: inhibits cell proliferations
– Endostatin: inhibits cell proliferation, migration & survival
– Angiostatin: inhibits cell proliferatio & induce endothelial apoptosis
Term
Drugs that inhibits matrix breakdown, the matrix metalloproteinase
inhibitors (MMPIs):
Definition
Marimastat; prinomastat
Term
Monoclonal antibodies vascular endothelial growth factors
(VEGFs)
Definition
Bevacizumab
Term
Monoclonal antibodies vascular endothelial growth factors
receptors (VEGFR)
Definition
– Sunitinib
Term

 

Risk of post-operative bleeding when platelet counts
is below _________ /mm3 .

Definition
Term
Spontaneous mucosal bleeding can occur when
platelet count is below _______ /mm3 . Risk of
bacteremia and/or bleeding associated with dental
procedures during chemotherapy.
Definition
Term
Dental Care during Cancer Chemotherapy
Definition
If treatment is required:
– Consult with oncologist;
– Neutrophil counts should be ≥1000/mm3 , if >2000/mm3
no antibiotic prophylaxis
– Clotting factors should be normal.
– Platelet counts is >75,000/mm3
Term
Agents for Mucositis
• These agents are employed for managing mucositis
but the evidence support their efficacy are weak
Definition

– Benzydamine (Topical)
    • anti-inflammatory, analgesic, antimicrobial (some)
– Topical analgesics
    • Vicious lidocaine, benzocaine, diphenyhydramine
formulated for topical applications.
        – Kaopetate, sulcrafate, milk of magnesia
– Systemic analgesics
    • Opioids, nonopioids, analgesic adjuvants

Term
_____ and ____ are used for the Tx of Xerostomia
Definition
– Pilocarpine (Salagen)
– Cevimeline (Evoxac)
Term
Agents minimizing Head and Neck Radiation damage
Definition
– Aminofostin
– Pilocarpine
– Cevimeline
Term
Aminofostin
Definition

Minimizes radiation damage

– prevents oxygen radical damages
– few clinical data, evidence is weak

Term
Pilocarpine and Cevimeline
Definition

Minimize radiation damage

– Muscarinic receptor agonist
– few clinical data, evidence is suggestive
but weak

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