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Block 7 week 1 > Cancer Chemotherapy 1&2 - Duan > Flashcards

Cancer Chemotherapy 1&2 - Duan Flashcards

1
Q

Name some characteristics of cancer cells.

A
  1. cancer is a disease of our own cells
  2. they exhibit shorter or accelerated cell cycles
  3. cancer cells undergo excessive proliferation
  4. exhibit higher activity of nucleic acid and protein synthesis
  5. exhibits altered cell-cell communication
  6. cancer cells are invasive and disrupt normal healthy tissues
  7. exhibit migration to distant sites - metastasis
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2
Q

Do cancer cell use the same nutrients and metabolic process abnormal host cell?

A

Yes

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3
Q

What stage of the cell cycle are most cells found in?

A

The G0 or resting phase.

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4
Q

Name, in order, the phases of the cell cycle.

A
  1. G0 - resting phase
  2. G1 - pre-synthesis or first gap phase
  3. S phase - DNA synthesis
  4. G2 - pre-mitotic interval or second gap phase
  5. M phase - mitosis
  6. back to G1 or G0
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5
Q

What phases of the cell cycle contain restriction points?

A
  1. G1

2. G2

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6
Q

What anti-cancer drug target the G1 phase of the cell cycle?

A

Mitomycin C

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7
Q

What anti-cancer drugs target the S phase of the cell cycle?

A
  1. Cytosine arabinoside
  2. Hydroxyurea
  3. 6-MP
  4. MTX
  5. 5-FU
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8
Q

What anti-cancer drug targets the G2 phase of the cell cycle?

A

Etoposide

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9
Q

Which anti-cancer drugs target the M phase of the cell cycle?

A
  1. Vincristine
  2. Vinblastine
  3. Taxanes
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10
Q

Name the general classes of anticancer drugs.

A
  1. Alkylating agents
  2. Antimetabolites
  3. Antibiotics
  4. Natural products
  5. Miscellaneous
  6. Hormones
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11
Q

What anti-cancer drugs are alkylating agents?

A
  1. Nitrogen mustards - Mechlorthamine, Cyclophosphamide, Ifosfamide
  2. Nitrosoureas - Carmustine, Streptozotocin, Lomustine
  3. Alkyl sulfonates - Busulfan
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12
Q

What anti-cancer drugs are antimetabolites?

A
  1. Folate antagonists - Methotrexate
  2. Purine antagonists - 6-Mercaptopurine
  3. Pyrimadine antagonists - 5- Fluorouracil
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13
Q

What anti- cancer drugs are antibiotics?

A
  1. Doxorubicin - also called Adriamycin
  2. Bleomycin - also called Bienoxane
  3. Mitomycin
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14
Q

What anti- cancer drugs are in the miscellaneous category?

A
  1. Platinum compounds - Cisplatin, Carboplatin
  2. Procarbazine
  3. L- Asparaginase
  4. Imatinib
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15
Q

What anti-cancer drugs are natural products?

A
  1. Vinca alkaloids

Etoposide

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16
Q

What anti-cancer drugs are hormones?

A
  1. Glucocorticoids

2. Tamoxifen

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17
Q

What is the mechanism of action of the alkylating agent class of drugs?

A

They impair cell function by forming covalent bonds with the amino, carboxyl, sulfhydryl and phosphate groups in biologically important molecules. This causes non-specific cross linking of DNA. The cell is damaged and will die during its next cell division.

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18
Q

Which position in DNA is particularly susceptible to alkylation?

A

The electron rich nitrogen at the N7 position of guanine.

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19
Q

Are alkylating agents cell cycle specific drugs?

A

No, they are active even for resting cells in G0.

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20
Q

Describe some characteristics of the nitrogen mustards.

A
  1. an alkylating agent
  2. main toxicity comes from DNA cross linkage
  3. the chloroethyl side chains of the nitrogen mustard molecule undergoes intramolcular cyclization and forms a carbonium ion intermediate
  4. the carbonium ion is a strong electrophile
  5. the electron donor (N7 of guanine residue in DNA or the SH of protein) undergoes nucleophilic attack by the carbonium ion and a complex is formed
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21
Q

What are the effects of alkylation of N7 of guanine residues in DNA?

A
  1. the guanine can mispair with a thymine residue during DNA synthesis - this leads to the substitution of an AT pair for the GC pair
  2. the guanine residue is excised and this leads to the opening of the imidazole ring of guanine
  3. with bifunctional alkylating agents another guanine residue is alkylated and cross linking of the two chains (or 2 spots on the same chain) results - or the link could be between a nucleic acid and a protein
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22
Q

What are the nitrogen mustard drugs used for?

A

They are used in combination with other drugs to treat lymphomas and leukemias.

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23
Q

What are the adverse reactions of the nitrogen mustard drugs?

A
  1. immunosuppresive
  2. carcinogenic
  3. teratogenic
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24
Q

Describe Mechlorethamine.

A
  1. a nitrogen mustard drug
  2. also called mustargen and mustine
  3. a nitrogen based analogue of mustard gas
  4. most reactive of the group
  5. used in combination with other drugs - MOPP to treat Hodgkin’s disease
  6. can cause infertility, bone marrow depression and GI toxicity (toxic to proliferating cells)
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25
Q

What is MOPP?

A

A combination of drugs including Mechlorethamine, Oncovin, Prednisone and Procarbazine that is used to treat Hodgkin’s disease.

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26
Q

What is another name for Oncovin?

A

Vincristine.

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27
Q

Hodgkin’s disease is treated with what?

A

The drugs MOPP.

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28
Q

Describe Cyclophosphamide.

A
  1. a nitrogen mustard drug
  2. also called Cytoxan, Neosar
  3. broad spectrum - given orally and IV
  4. is a prodrug that is converted to phosphor amide mustard and acrolein by cytochrome P450
  5. causes cross-linking of DNA via N7 of guanine
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29
Q

What is Cyclophosphamide used for?

A
  1. non-neoplastic diseases like nephrotic syndrome
  2. non-Hodgkin’s lymphomas
  3. maintenance therapy for acute lymphoid leukemia (ALL)
  4. adjuvant therapy in breast cancer
  5. carcinoid
  6. neuroblastoma
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30
Q

What are the adverse side effects of Cyclophosphamide?

A
  1. bone marrow suppression
  2. alopecia
  3. GI disturbances
  4. hemorrhagic cystitis
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31
Q

Describe Ifosfamide.

A
  1. an analog of cyclophosphamide
  2. also called Ifex
  3. activated in the liver by ring hydroxylation
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32
Q

What is Ifosfamide used for?

A
  1. used as part of multi drug regimen to treat germ cell testicular cancer, pediatric and adult sarcomas and other cancers such as cervical, lung, bone, ovarian and breast
  2. used in combination with Mesna to reduce its urinary toxicity
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33
Q

What are the adverse side effects of Ifosfamide?

A
  1. similar to cyclophosphamide but with greater platelet suppression
  2. severe urothelial damage and internal bleeding (if not used with Mesna)
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34
Q

Another class of drugs that are alkylating agents is the Nitrosoureas. What is their MOA?

A

They spontaneously degrade to form 2-chloroethylcarbonium ion which liberates isocyanates that attach carbamoyl groups to lysine residues of proteins. They also cross link DNA strands and break DNA strands.

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35
Q

What are the adverse side effects of Nitrosoureas?

A
  1. highly carcinogenic and mutagenic
  2. cause profound, cumulative myelosuppression
  3. cause renal failure with long-term use
  4. cause alopecia
  5. are hepatotoxic
  6. cause pulmonary toxicity
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36
Q

Describe Carmustine, Lomustine and Semustine.

A
  1. a nitrosoureas
  2. exhibit high lipophilicity - can cross BBB
  3. both lomustine and semustine are orally effective
  4. used to treat brain tumors such as gliomas, glioblastoma multiform, medulloblastoma, astrocytoma
  5. used to treat GI neoplasms
  6. alternative drugs in treating Hodgkin’s disease
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37
Q

Describe Streptozotocin.

A
  1. a nitrosourea
  2. water soluble but not orally effective
  3. particularly toxic to pancreatic islet cells
  4. used to treat insuloma (pancreatic islet cell carcinoma, carcinoid, excessive insulin secretion)
  5. used to treat metastatic cancer of pancreatic islet cells
  6. can be used to cause experimental diabetes in lab animals
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38
Q

What is the MOA of Streptozotocin?

A

It methylates RNA and DNA and is particularly toxic to pancreatic islet cells.

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39
Q

Describe Bisulfan.

A
  1. an alkyl sulfonate
  2. selectively myelosuppressive by inhibiting granulocytopoiesis
  3. used to treat chronic myelogenous leukemia (CML) and other myeloproliferative disorders
  4. causes myelosuppression
  5. causes ‘Busulfan lung’ which is rare but fatal pulmonary fibrosis so is contraindicated in pt’s with pulmonary disease/condition
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40
Q

Describe the Antimetabolite class of anti-cancer drugs.

A
  1. structurally similar to important endogenous molecules in the synthesis of DNA and RNA
  2. has three general groups
  3. act as enzyme inhibitor
  4. they are S-phase specific because they slow down the synthesis of nucleic acids
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41
Q

What are the 3 general groups of Antimetabolite cancer drugs?

A
  1. purine analogs
  2. pyrimadine analogs
  3. folic acid analogs
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42
Q

Name one purine analog cancer drug. What is it’s MOA?

A

6- Mercaptopurine (6-MP)
This drug is a structural analog of adenine that is activated by an enzyme (HGPRT) to convert to a nucleotide called 6-TIMP. 6-TIMP inhibits the conversion of IMP to adenine and guanine and blocks the first step in de novo synthesis of purines - thus blocking DNA replication and RNA transcription.

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43
Q

What is the clinical use of 6-MP?

A

It is used for maintenance therapy of acute lymphoid leukemia (ALL) in children.

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44
Q

What are the adverse effects of 6-MP?

A
  1. bone marrow suppression
  2. immunosuppression
  3. GI disturbances
  4. liver toxicity
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45
Q

How does the body develop resistance to 6-MP?

A
  1. increased breakdown of 6-TIMP by alkaline phosphatase

2. decreased activation of the drug via decreased or lack of the enzyme HGPRT

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46
Q

Name another Purine analog drug. What is it’s MOA?

A

6-Thioguanine
This drug is converted to 6-TGMP by the enzyme HGPRT. 6-TGMP becomes incorporated into DNA as dTGTP. It is also an enzyme inhibitor.

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47
Q

What is 6-Thioguanine used for?

A

It is used to treat leukemias - especially acute granulocytic leukemia. For treatment of AGL it is used in combo with Cytarabine.

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48
Q

What are the adverse effects of 6-Thioguanine?

A
  1. bone marrow suppression
  2. mild nausea
  3. resistance can develop - via decreased conversion of the prodrug form
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49
Q

Describe 5- Fluorouracil.

A
  1. a Pyrimidine antagonist
  2. bioactivated to 5FdUMP in the body
  3. 5FdUMP covalently complexes with folic acid
  4. the complex then inhibits thymidylate synthesis causing decreased dTMP and thus termination of DNA synthesis
  5. requires enzymatic conversion to a nucleotide via ribosylation and phosphorylation to exert its cytotoxic activity
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50
Q

What is 5-FU used for?

A
  1. basal cell carcinoma
  2. solid tumors of the digestive system such as tumors in the esophagus, stomach, colon, pancreas and liver
  3. tumors of the breast, over and bladder
  4. lymphomas
  5. keratosis
51
Q

What are the adverse effects of 5-FU?

A
  1. bone marrow depression - leucopenia, thrombocytopenia
  2. alopecia
  3. GI disturbance
  4. hand and foot syndrome - Palmar-Plantar Erythrodysesthesia
52
Q

Describe Cytarabine, (Cytosine arabinoside, araC).

A
  1. administered continuous IV infusion
  2. S-phase specific - converted to nucleoside which terminates DNA chain elongation
  3. is a pyrimidine antagonist drug - cytidine analog
53
Q

What are clinical uses and side effects of Cytarabine?

A
  1. first line choice to treat acute myelogenous leukemia (AML) and lymphomas
  2. side effects include bone marrow depression, severe bone marrow hypoplasia
54
Q

Describe Methotrexate (MTX).

A
  1. a folate antagonist
  2. S-phase specific
  3. is a structural analog of folic acid so it reversibly inhibits dihydrofolate reductase resulting in decreased dTMP
  4. decreased dTMP inhibits the folate enzymes of de novo purine and thymidylate synthesis
55
Q

What is MTX used for?

A
  1. acute lymphoblastic leukemia (ALL)
  2. choriocarcinoma- MTX treatment represents the first and consistent cure of a solid tumor
  3. severe rheumatoid arthritis
  4. psoriasis
  5. part of a multidrug regiment for other cancers
56
Q

What are the adverse effects of MTX?

A
  1. neurotoxicity (with intrathecal use)
  2. nephrotoxicity
  3. interstitial pneumonitis
  4. hepatotoxicity
  5. resistance to MTX is developed via decreased uptake of the drug
57
Q

Describe how the drug Leucovorin is used with MTX.

A

Leucovorin is an active analog of folic acid. Normal cells have a faster uptake of this analog than resistant sarcoma cells. This drug is administered with MTX to selectively rescue normal cells from the adverse effects of MTX. Leucovorin can also compete with MTX for the sam transport process into the cell It is usually given 24 hours after MTX so that MTX can have a therapeutic effect on cancer cells.

58
Q

Which antibiotic drugs are used as anti cancer drugs?

A
  1. Doxorubicin (Adriamycin)
  2. Daunorubicin
  3. Epirubicin
  4. Idarubicin
  5. Bleomycin
  6. Mitomycin C
  7. Mitoxantrone
59
Q

What is the MOA of Doxorubicin?

A
  1. binds to DNA where it can inhibit the progression of the enzyme topoisomerase II
  2. topoisomerase II functions by unwinding DNA for transcription
  3. also reduces O2 with semiquinones to produce free radicals, intercalates DNA and causes plasma membrane disruption
60
Q

What are the adverse effects of Doxorubicin?

A
  1. acute - heart arrhythmias, bone marrow suppression, alopecia and GI disturbance
  2. irreversible - dose related cardiomyopathy, CHF, dilated cardiomyopathy and possible death
61
Q

Describe Doxorubicin cardiotoxicity.

A
  1. characterized by a dose-dependent decline in mitochondrial oxidative phosphorylation.
  2. interacts with iron to produce ROS’s and damages myocytes (myofibrillar loss and cytoplasmic vacuolization)
  3. even if given as a child can develop dilated cardiomyopathy years later
62
Q

How can the cardiotoxic effects of Doxorubicin be mitigated?

A

It is used in combination with an iron chelator called Dexrazoxane.

63
Q

Describe Daunorubicin.

A
  1. can be used as starting material for manufacture of synthetic doxorubicin, epirubicin and idarubicin
  2. used most commonly to treat specific types of leukemia such as AML and ALL
  3. commonly used to treat Hodgkins disease, soft tissue sarcomas, breast cancer, lung cancer and Kahlers disease
  4. really effective in treating breast, ovary, endometrial, bladder, thyroid and lung cancers
64
Q

What is epirubicin used to treat?

A

breast cancer

65
Q

What is idarubicin used to treat?

A

AML - acute myeloid leukemia

66
Q

Describe Bleomycin.

A
  1. a glycosylated, linear nonribosomal peptide antibiotic produced by the bacteria Streptomyces verticillus
  2. Bleomycin refers to a family of structurally related compounds
  3. Bleomycin A2 and B2 are used as anticancer drugs
  4. used in multi drug regimens in concert with MOPP to treat advanced Hodgkins disease - can be curative (50-80%)
67
Q

What is the MOA of the Bleomycin family of drugs?

A
  1. chelates metal ions - primarily iron - producing a pseudo-enzyme that reacts with oxygen to produce ROS’s that break single and double stranded DNA chains in the G2 phase of the cell cycle
  2. also inhibits incorporation of thymidine into DNA strands
68
Q

What is Bleomycin used for?

A
  1. combined with vinblastine and cisplatin to treat advanced testicular cancer, lymphomas, squamous carcinomas of the cervix, head, neck and lungs
69
Q

What are the adverse effects of Bleomycin?

A
  1. lung toxicity - potentially fatal
  2. erythema or other skin toxicities such as rash, hyper pigmentation and Raynaud’s phenomenon
  3. fever
  4. alopecia
70
Q

Does Bleomycin cause bone marrow suppression/toxicity?

A

No.

71
Q

What is ABVD?

A

A multidrug regimen used in conjunction with MOPP to treat stage III and IV Hodgkin’s disease. The drugs are Adriamycin, Bleomycin, Vinblastine, and Dacarbazine.

72
Q

Describe Mitomycin C.

A
  1. activated to a bifunctional alkylating agent which cross links DNA
  2. produces ROS’s which cause cleavage of DNA
  3. works in the G1 phase of the cell cycle
73
Q

What are the clinical uses of Mitomycin C?

A
  1. adenocarcinomas of the breast, colon, stomach and lung

2. not as effective as other antibiotics

74
Q

What are the effects of Mitomycin C?

A
  1. severe, delayed and cumulative bone marrow suppression
  2. nausea
  3. renal toxicity
  4. carcinogenic (delayed effect)
75
Q

Describe Etoposide.

A
  1. a plant alkaloid (May Apple)
  2. arrests the cell cycle at the S to G2 interface via inhibition of Topoisomerase II
  3. binds to Topoisomerase II complex and prevents it from resealing double stranded DNA breaks
76
Q

What are the clinical uses of Etoposide?

A
  1. testicular cancer
  2. lung cancer
  3. lymphomas
  4. acute nonlymphocytic leukemia
  5. breast cancer
77
Q

What are the adverse side effects of Etoposide?

A
  1. bone marrow suppression
  2. allergy with possible severe anaphylaxis
  3. loss of hair
  4. GI disturbances
78
Q

Name the Vinca Alkyloids.

A
  1. Vincristine (Oncovin)

2. Vinblastine

79
Q

What is the MOA of the Vinca alkaloids?

A
  1. bind to tubulin dimers and inhibit their polymerization
  2. leads to the disruption of mitotic spindle formation and thus blocks cell division, DNA synthesis and intracellular transport
  3. M phase specific - cell cycle stops in metaphase of mitosis
80
Q

What are the clinical uses of Vincristine?

A
  1. children’s tumors
  2. Wilm’s tumor
  3. Ewing’s sarcoma
  4. ALL
  5. neuroblastomas
81
Q

What are the clinical uses of Vinblastine?

A
  1. testicular cancer

2. lymphomas - both Hodgkins and non-Hodgkins

82
Q

Describe Cisplatin.

A
  1. molecule composed of platinum complexed with chlorine and amine groups
  2. the chlorine atoms can dissociate and the platinum amine complex binds to DNA in a manner similar to bifunctional alkylating agents
  3. causes DNA cross linking
83
Q

Describe Carboplatin.

A
  1. molecule composed of platinum complexed to a complex moiety
  2. like Cisplatin, liberation of the platinum amine complex binds to DNA and causes cross linking
  3. slower acting than Cisplatin
84
Q

What are the clinical uses and adverse effects of Cisplatin?

A
  1. broad spectrum agent with very good activity against epithelial cancers
  2. very effective against testicular and ovarian cancer - used in combo with bleomycin and vinblastine when treating these
  3. adverse effects - bone marrow suppression, GI disturbance, nephrotoxicity, ottoxicity
85
Q

What are the clinical uses and adverse effects of Carboplatin?

A
  1. currently used to treat sensitive tumors in individuals who cannot tolerate cisplatin because of impaired renal function
  2. adverse effects - bone marrow suppression, less nephrotoxic than cisplatin
86
Q

Describe Procarbazine.

A
  1. the drug is auto oxidized in the body and the toxic oxygen and hydroxyl free radicals that degrade DNA
  2. can also transmethylate guanine residues in DNA
  3. MOA’s lead to chromosomal breakage
87
Q

What is Procarbazine used for?

A
  1. part of MOPP regimen to treat Hodgkins disease

2. used also to treat non-Hodgkin’s lymphomas and oat-cell carcinoma

88
Q

What are the side effects of Procarbazine?

A
  1. monoamine oxidase inhibition
  2. Disulfiram-like reaction to alcohol
  3. causes neurological effects such as drowsiness and sedation
89
Q

Describe L-Asparaginase.

A
  1. an enzyme that degrades asparagine and glutamine (amino acids essential to some leukemia cells)
  2. is a normal enzyme produced by some cells
  3. the sensitive leukemia cells lack asparagine synthetase so if it is not available exogenously due to the drug then DNA synthesis halts and the cells die
90
Q

What is L-asparaginase used for?

A

Used to treat acute lymphoid leukemia (ALL).

91
Q

What are the adverse effects of L-asparaginase?

A
  1. hypersensitivity
  2. nausea
  3. liver toxicity
  4. pancreatic toxicity
  5. some tumor cells develop resistance via de novo induction of asparagine synthetase
92
Q

How can hormones be used as anticancer agents?

A

Tumors arising from hormone target tissues often retain responsiveness to growth promoting effects of hormones. These tumors may be inhibited by altering the hormone supply through modification.

93
Q

How can hormone supply be modified in some cancer treatments?

A
  1. ablation of the hormone secreting organ
  2. other hormones that suppress the production of the supporting hormone can be modified
  3. hormone antagonists can be introduced
  4. high doses of the supporting hormone can also inhibit some tumor growth
94
Q

Describe how glucocorticoids are used.

A
  1. high doses of prednisone is toxic to lymphocytes and can be used in treating acute and chronic lymphocytic leukemia, lymphomas and multiple myelomas
  2. part of MOPP regimen
95
Q

Describe how Tamoxifen is used.

A
  1. used to treat tumors that have a high concentration of estrogen receptors
  2. tamoxifen is a competitive antagonist of the estrogen receptor
  3. orally effective and concentrates in estrogen target tissues such as ovaries, vaginal epithelium and breast
  4. adverse effects - hot flashes, hypercalcemia
96
Q

Describe Imatinib (Gleevac).

A
  1. MOA - binds to ATP binding site on tyrosine kinase and inhibits it
  2. This tyrosine kinase is tumor specific - it is located on the Bcr-Abl oncoprotein which is a fusion protein expressed from the fusion gene Bcr-Abl
  3. the tumor specific tyrosine kinase is involved in the pathogenesis of chronic myelogenous leukemia
97
Q

What is the clinical use of Imatinib?

A

This drug is used to tray Philadelphia Chromosome-positive chronic myelogenous leukemia. It is used as a second line drug for the chronic phase of CML when it is not adequately controlled with interferon alpha. It is a first line drug for accelerated phase or blast crisis. Can also be used for tumors that over express c-kit or platelet-derived growth factor kinase malignant gastrointestinal stromal tumors.

98
Q

What are the adverse side effects of Imatinib?

A
  1. diarrhea and other GI upsets
  2. ankle and periorbital edema due to water retention
  3. myalgia
  4. is a substrate and powerful inhibitor of some cytochrome P450’s
  5. tumor cells develop resistance via mutation in bcr-abl kinase gene
99
Q

Describe Iressa.

A
  1. orally active tyrosine kinase inhibitor selective for the epidermal growth factor receptor tyrosine kinase
  2. causes the EGF receptor signaling to be over activated in sensitive tumors
  3. in clinical trials to treat solid tumors of the head, neck, breast and non-small cell lung cancer
  4. adverse effects - diarrhea, skin rashes
100
Q

What is immunotherapy?

A

Any intervention to enhance the body’s natural ability to defend itself against malignant tumors.

101
Q

Name some types of immunotherapy.

A
  1. interferons
  2. interleukins
  3. colony-stimulating factors
  4. monoclonal antibodies
  5. gene therapy
  6. nonspecific immunomodulators
  7. vaccines such as those containing cancer specific antigens and other components that boost immunity - i.e. dendritic cell vaccines
102
Q

Describe Herceptin.

A
  1. monoclonal antibody humanized against HER-2 antigen that is over expressed on tumor cell surfaces in 25% of breast cancer patients
  2. HER-2/neu/erbB2 overexpression marke an aggressive estrogen Rezeptor-negative form of breast cancer
  3. used in IV infusion in combo with paclitaxel for metastatic breast cancer
  4. adverse effects - flushing, bronchoconstriction, skin rash, cardiotoxicity, infusion related hypotension
103
Q

Which drug targets the G1 phase of the cell cycle?

A
  1. Mitomycin C - bifunctional alkylate that cross links DNA
104
Q

Which drugs target the S phase of the cell cycle?

A
  1. cytosine arabinoside
  2. hydroxyurea
  3. 6-MP
  4. MTX
  5. 5-FU
    These drugs block DNA synthesis
105
Q

Which drugs target the M phase of the cell cycle?

A
  1. vincristine
  2. vinblastine
  3. taxanes
    These drugs block mitotic spindle formation
106
Q

Which drug targets the G2 phase of the cell cycle?

A

Etoposide - inhibits topoisomerase II and causes DNA degradation.

107
Q

Which drugs are cell cycle non-specific drugs?

A
  1. alkylating agents - nitrogen mustards and nutrosoureas, Busulfan
  2. antiobiotics - doxorubicin, mitoxantrone, dactinomycin, bleomycin
  3. cis-platinum, procarbazine, dacarbazine
108
Q

Name the cancer therapeutic modalities.

A
  1. surgury - 1/3 of all patients receive this therapy
  2. radiotherapy - 1/2 of early cancers can be cured using this therapy
  3. chemotherapy - 1/2 of all pt’s undergo but it is only able to cure about 10-15% of all cancer pt’s
109
Q

what are the types of chemotherapy?

A
  1. cytotoxic
  2. endocrine
  3. biological
  4. gene therapy
110
Q

What are the main goals of cancer chemotherapeutics?

A
  1. cure the patient if possible (disappearance of any evidence of tumor for several years and restoration of normal life span)
  2. shrinkage of tumor - eliminate cancer cells without effecting normal tissues
  3. treatment of symptoms to improve quality and duration of life
111
Q

Describe the effects of tumor burden, scheduling, dosing and initiation and duration of treatment on patient survival.

A
  1. surgery is the best if possible because it decreases the tumor burden and chemotherapy can remove persistent secondary tumors
  2. intense and frequent treatments can reduce the tumor burden when the kill rate is greater than the growth rate.
  3. infrequent scheduling of treatment courses can prolong survival but does not cure the cancer.
112
Q

Describe some characteristics of chemotherapy.

A
  1. it has limited effectiveness - after successful shrinkage of tumor, tumor cells become resistant and side effects prevail over benefits and tx stopped which allows tumor to grow again
  2. it has a narrow therapeutic index so multi drug regimens are used
113
Q

What are some benefits of multi drug regimens?

A

They have different:

  1. mechanisms - may have synergistic effects
  2. sites of action
  3. toxicity - intermittent doses permit recovery from acute toxicities
  4. work at various phases of the cell cycle
  5. combinations are usually more effective than mono therapy and reduce the probability that resistant clones will emerge
114
Q

How is the cell cycle important in chemotherapy?

A
  1. tumor cells are more prone to cytotoxic effect of cancer drugs due to their faster rate of cell division
  2. MOA of anticancer drugs kill both actively growing tumor cells and normal cells but tumor cells grow faster so there is some selective toxicity
  3. normal cells with faster cell cycles are very susceptible to anti cancer drugs - i.e. hair follicles and cells of bone marrow
115
Q

Name some acute effects of anticancer drugs due to their toxicity to normal cells with fast cell cycles.

A
  1. bone marrow toxicity - more susceptible to infection and hemorrhage
  2. GI toxicity - causes diarrhea
  3. Hair follicle toxicity - loss of hair
  4. Germline cell toxicity - infertility
116
Q

Name some chronic effects of anticancer drugs due to their toxicity to normal cells with fast cell cycles.

A
  1. cardiomyopathy
  2. neurotoxicity
  3. GI distress
  4. nephrotoxicity
  5. mutagenesis
  6. carcinogenesis
117
Q

Describe the schedule of administration of chemotherapy.

A
  1. typically consists of a cycle of drug treatment followed by a drug-free period
  2. pattern may be repeated several times
  3. dose and duration depends on pharmacokinetics, cell cycle phase specificity of drug, pt’s general health, type of cancer treated
118
Q

Name the types of multi drug resistance.

A
  1. primary resistance - some tumor cells that frequently undergo spontaneous mutation may not respond to initial therapies
  2. acquired resistance - appears or develops during therapy
119
Q

How can acquired resistance develop?

A
  1. result of amplification of target genes, multi drug resistance gene (MDR1)
  2. changes in cellular target of drugs - i.e. less affinity for drug
  3. changes in transport of drugs
  4. changes in activating enzymes of certain drugs
120
Q

What is p-glycoprotein?

A

A protein that has transport functions in the membrane for drugs. It can be blocked by MDR gene modulators or chemosensitizers.

121
Q

Name some multi drug regimens commonly used.

A
  1. ABVD - used to treat Hodgkins disease
  2. MOPP - used to treat Hodgkin’s disease

MOPP alternating with ABVD is a defined cyclical schedule used as front line treatment for advanced Hodgkin’s disease

122
Q

What drugs are a part of MOPP?

A
  1. metchlorethamine
  2. oncovin
  3. procarbazine
  4. prednisone
123
Q

What drugs are a part of ABVD?

A
  1. Adriamycin
  2. Bleomycin
  3. Vinblastine
  4. Dacarbazine

Block 7 week 1 (3 decks)

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