Cancer Treatment Flashcards
(181 cards)
1
Q
Antimetabolites
A
cytarabine, 5-fluorouracil, mercaptopurine, methotrexate, thioguanine
2
Q
Antitumor Antibiotics
A
bleomycin, dactinomycin, doxorubicin
3
Q
Alkylating Agents
A
carmustine, dacarbazine, lomustine, mechlorethamine
4
Q
Mitotic Inhibitors
A
docetaxel, paclitaxel, vinblastine, vincristine
5
Q
Steroid Hormones and Antagonists
A
aminoglutethimide, anastrozole, bicalutamide, exemestane, flutamide, goserelin, letrozole, leuprolide, nilutamide, prednisone, tamoxifen
6
Q
Monoclonal antibodies
A
bevacizumab, retuximab, trastuzumab
7
Q
Other Anticancer drugs
A
carboplatin, cisplatin, interferons, oxaliplatin
8
Q
T/F 25 percent of the US population will face a diagnosis of cancer
A
true
9
Q
What are three types of treatment for cancer?
A
surgery, local radiation, systemic chemotherapy
10
Q
What is the overall 5 year survival rate for cancer patients?
A
65%
11
Q
What is the goal of chemotherapy?
A
cause a lethal cytotoxic event or apoptosis in the caner cell, arresting the tumor progression
12
Q
Where is the chemotherapy attack directed?
A
DNA or metabolic sites essential to cell replication
13
Q
T/F there are steep dose-response curves for both toxic and therapeutic effects
A
true, chemo effects all kinds of proliferating cells not just malignant cells
14
Q
What is the ultimate goal of treatment?
A
a cure, long term disease free survival, requires eradication of every neoplastic cell
15
Q
What is the goal of cancer treatment if a cure is not attainable?
A
control of the disease, stop the cancer from enlarging and spreading and allow patient to maintain a normal existence
16
Q
How is the neoplastic cell burden usually initially reduced?
A
surgery and or radiation, followed by chemotherapy, immunotherapy etc
17
Q
What are indications for chemotherapy?
A
when tumor cells are not amenable to surgery, as supplemental treatment after surgery or radiation, to shrink tumor prior to surgery, or to prolong remission
18
Q
How does the cell growth cycle relate to tumor susceptibility?
A
rapidly dividing cells are usually more susceptible, while non-proliferating cells (G0) usually survive toxic effects of therapy
19
Q
How does the tumor growth rate work?
A
growth rate of tumors is initially rapid but slows as tumor size increases because nutrients and oxygen decrease
20
Q
What cell cycle “stage” does surgery or radiation shift remaining cell types to?
A
active proliferation, making them more susceptible to chemotherapy
21
Q
What is log kill?
A
destruction of cancer cells follows first-order kinetics so a given dose destroys constant fraction of cells
22
Q
What is a pharmacologic sanctuary?
A
some tumor cells can hide in tissues where chemotherapeutic agents can not enter, like the CNS
23
Q
What two treatments are aimed at “finding” the tumor?
A
radiation and alternative administration of drugs
24
Q
What is a typical cancer treatment protocol?
A
combination of drugs is more successful, use agents with different toxicities and different MOAs
25
T/F if two drugs are combined for cancer therapy that have similar toxicities, you must decrease the dose of both
true
26
What are the advantages of combination drug treatment?
provide maximal killing with tolerated toxicity, effective against broad cell lines, may delay development of resistant cell lines
27
T/F some cells are inherently resistant to anticancer drugs
true
28
What are two mechanisms by which multidrug resistance occurs?
transmembrane protein (p-glycoprotein) can pump anticancer drugs out of tumor cells, high concentration of some drugs can inhibit the pump
29
Which cells are particularly susceptible to toxicity?
those that undergo rapid proliferation: lining of cheeks, bone marrow, GI mucosa, hair follicles
30
T/F chemotherapeutic agents have a broad therapeutic index
false, narrow
31
What are the most common adverse effects to cancer treatment?
severe vomiting, bone marrow suppression, alopecia and myelosuppression
32
What are treatment induced tumors?
chemotherapeutic agents are mutagens, neoplasms can arise 10 or more years after the original cancer was cured, especially with alkylating agents
33
What is the MOA of antimetabolites?
interefere with the availability of normal nucleotide base precursors by either inhibiting synthesis or competing with them in DNA or RNA synthesis
34
Are antimetabolites cell cycle specific or not?
cell cycle specific, maximal effects in S phase
35
What is dihydrofolate reductase?
the enzyme that converts folic acid to active form (tetrahydrofolic acid) which is essential for cell replication
36
What is the MOA of methotrexate?
dihydrofolate reductase antagonist, leads to decreased production of required nucleic compounds aka DNA, RNA, and protein synthesis is depressed leading to cell death
37
How can you reverse methotrexate?
use a thousandfold excess dihydrofolate or administer leucovorin
38
What is leucovorin?
it has a similar structure to folic acid and bypasses blocked enzyme and replenishes folate pool
39
Which cells are resistant to methotrexate?
non-proliferating cells
40
What drug in low doses can treat some inflammatory diseases as an antimetabolite?
methotrexate
41
What three inflammatory diseases can methotrexate treat?
severe psoriasis, rheumatoid arthritis, Crohn's disease
42
How is methotrexate administered?
oral, IM and IV (intrathecal)
43
Does methotrexate penetrate the CNS?
no, requires intrathecal
44
Why must a patient on methotrexate be hydrated?
to prevent renal toxicity which can lead to crystalluria
45
What are the adverse effects of methotrexate?
GI upset, toxicities in constantly renewing tissues (rash, urticaria, alopecia, stomatitis, erythemia), renal damage, cirrhosis
46
What is the adverse effect of methotrexate in children?
pulmonary toxicity
47
What are the contraindications of methotrexate?
pregnancy
48
What is the MOA of mercaptopurine?
nucleotide formation, inhibition of protein synthesis, and incorporation into nucleic acids for RNA and DNA
49
What are pharmacokinetic considerations for mercaptopurine?
incomplete absorption orally, reduced bioavailability by first pass... still given orally though
50
What are the adverse effects of mercaptopurine?
bone marrow depression, anorexia + GI upset, jaundice
51
What is the MOA of thioguanine?
same as 6-MP, nucleotide formation, inhibition of protein synthesis and incorporation into nucleic acids for RNA and DNA
52
What are the pharmacokinetic considerations of thioguanine?
incomplete oral absorption w/ first pass, some people accumulate higher concentrations of metabolites leading to high myelosuppression and secondary malignancies (genotyping recommended)
53
What are the adverse effects of thioguanine?
dose-related bone marrow depression and risk of liver toxicity with long-term use
54
Is thioguanine used as a maintenance therapy?
no
55
What is the MOA of 5-fluorouracil?
enters cell through carrier-mediated transport system, forms a molecular complex that deprives the cell of thymidine stoping DNA synthesis
56
What is given in combination with 5-FU (fluorouracil)?
leucovorin which helps 5FU work longer
57
How is 5FU administered?
IV or topically
58
What are some reasons 5FU is given topically?
skin cancer, prevention of scar tissue formation in surgery, in some ocular surgeries
59
Does 5FU penetrate the CNS?
yes
60
How is 5FU excreted?
kidney and lungs
61
What are the adverse effects of 5FU?
GI upset, ulceration of oral and GI mucosa, bone marrow depression, anorexia
62
What is the MOA of cytarabine?
enters cell via carrier-mediated process and inhibits DNA polymerase and also can be incorporated into cellular DNA
63
Which cell cycle phase does cytarabine act during?
S phase specific
64
How is cytarabine administered?
IV only, new preparation allows penetration to CSF
65
How is cytarabine excreted?
kidney
66
What are the adverse effects of cytarabine?
GI upset, sever myelosuppression, hepatic dysfunction, CHEMICAL CONJUNCTIVITIS at high doses
67
What is the MOA of antitumor antibiotics?
cytotoxic due to interactions with DNA that prevent RNA synthesis and leads to the formation of toxic free radicals
68
Are anti-tumor antibiotics cell-cycle specific?
mostly no
69
What is the first antibiotic to find use in tumor chemotherapy?
dactinomycin
70
What is dactinomycin sometimes combined with?
methotrexate
71
What is the MOA of dactinomycin?
inserts into double helix and interferes with RNA polymerase
72
How is dactinomycin administered?
IV
73
Does dactinomycin penetrate the CSF?
no
74
How is dactinomycin excreted?
via bile
75
What are the adverse effects of dactinomycin?
bone marrow suppression, immunosuppression, GI upset, alopecia, stomatitis, sensitization to radiation
76
What is doxorubicin?
one of the most widely used anticancer drugs-- the red devil
77
What are the analogues of doxorubicin?
idarubicin and epirubicin
78
What is the MOA of doxorubicin?
induce cytotoxicity and produce free radicals that damage the cells' DNA
79
How is doxorubicin administered?
IV, deactivated in the GI tract
80
What does extravasation of doxorubicin lead to?
tissue necrosis
81
How is doxorubicin metabolized and excreted?
extensive liver metabolism and bile excretion
82
Why is doxorubicin the red devil?
veins may appear dark red surrounding site of infusion and urine will be red
83
What are the adverse effects of doxorubicin?
CARDIOTOXICITY (irreversible), bone marrow suppression, stomatitis, GI upset, severe alopecia
84
What is the MOA of bleomycin?
oxidative scission of DNA
85
Is bleomycin cell cycle specific?
yes, causes cells to accumulate in G2
86
What is bleomycin used to treat?
testicular cancers
87
How is bleomycin administered?
subc, IM, IC
88
What is true of bleomycin absorption?
inactivating enzyme is present in liver and spleen, low in lungs, absent in skin
89
How is bleomycin excreted?
kidney
90
What are the adverse effects of bleomycin?
PULMONARY TOXICITY, alopecia, fever and chills, hypertrophic skin changes and HYPERPIGMENTATION
91
What is the MOA of alkylating agents?
cause alkylation of DNA by addition of carbon chain to beginning of molecules which alters structure and function
92
Are alkylating agents cell cycle specific?
no, used mainly for slow growing tumors
93
T/F all alkylating agents are mutagenic and carcinogenic
true, can lead to secondary malignancies, especially leukemia
94
What drug was developed as mustard gas during WWI?
meclorethamine
95
What is the MOA of meclorethamine?
transported into cell, cross links with DNA guanine bases, cause strand breakage and occasional miscoding mutations
96
What are the pharmacokinetic considerations of meclorethamine?
very unstable, blistering agent, only given IV, and has almost no drug excretion
97
What are the adverse effects of meclorethamine?
severe GI, severe bone marrow depression, latent viral infections due to immunosuppression
98
What is the MOA of carmustine and lomustine?
alkylation of DNA that inhibits replication and eventually RNA and protein synthesis
99
What are carmustine and lomustine primarily used for?
treatment of brain tumors since they penetrate CNS
100
What are closely related nitrosoureas specifically toxic to beta cells of the pancreas?
carmustine and lomustine
101
When are carmustine and lomustine cytotoxic?
in actively dividing cells, alkylate DNA in all cell cycle phases
102
How are carmustine and lomustine administered?
IV and oral respectively
103
How are C and L excreted?
kidney
104
What are adverse effects of C and L?
delayed hematopoietic depression (decreased formation of blood cells), development of aplastic marrow, renal toxicity and pulmonary fibrosis
105
What is dacarbaxine used to treat?
melanoma
106
What is the MOA of dacarbazine?
attacks nucleophilic groups in DNA and must undergo biotransformation to an active metabolite
107
How is dacarbazine administered?
IV
108
What are the adverse effects of dacarbazine?
GI, myelosuppression, hepatotoxicity
109
What are mitotic spindles?
chromatin and microtubules needed for movement of DNA in cell division
110
What is the MOA of vincristine and vinblastine?
bind to microtubular protein and prevent polumerization aka no formation of spindle
111
Are vincrisitne and vinblastine cell cycle specific?
yes
112
How are V and V administered?
IV
113
T/F V and V are metabolized by the P450 system
true
114
How are V and V excreted?
bile and feces
115
What are adverse effects of V and V?
hyperuricemia (gout), GI, alopecia, phlebitis or cellulitis if extravasation occurs
116
What is the MOA of paclitaxel and docetaxel?
bind to tubulin subunit and promote stabilization of microtubules (overly stable microtubules are nonfunctional)
117
What are the pharmacokinetics of paclitaxel and docetaxel?
IV infusion, P450 metabolism and biliary excretion
118
What are the adverse effects of paclitaxel and docetaxel?
neutropenia, peripheral neuropathy, hypersensitivity reaction
119
Which typical adverse effect is uncommon with paclitaxel and docetaxel?
vomiting and diarrhea, instead there is fluid retention
120
What is the contraindication of paclitaxel and docetaxel?
cardiac disease
121
Steroid hormone sensitive tumors may be ___ or ____
hormone responsive or dependent (or both)
122
What is hormone responsive?
tumor regresses following treatment with specific hormone
123
What is hormone dependent?
removal of hormone results in tumor regression
124
What is prednisone used for?
treatment of lymphomas, used to induce remission
125
What is the MOA of prednisone?
triggers production of specific proteins that reduce cell growth and proliferation
126
What are the pharmacokinetics of prednisone?
readily absorbed orally, liver metabolism, excreted in urine
127
What are the adverse effects of prednisone?
predisposed patient to infection, hyperglycemia, cataract formation, increased IOP, osteoporosis, mood changes
128
What adverse effects are the same for all corticosteroids and anti-inflammatory cancer tx?
predispose to infection, hyperglycemia, cataract formation, increased IOP, osteoporosis, mood changes
129
What is tamoxifen?
an estrogen antagonists used for breast cancer
130
T/F tamoxifen can be used prophylactically in women at high risk
true, but must be discontinued after 5 years or drug resistant tumors can develop
131
What is the MOA of tamoxifen?
binds estrogen receptor as antagonist preventing RNA synthesis, results in depletion of estrogen receptors
132
What is tamoxifen given with in premenopausal women?
an agent that lowers estrogen levels since the drug competes with estrogen
133
Is tamoxifen cell cycle specific?
no
134
How is tamoxifen administered?
orally
135
How is tamoxifen metabolized and excreted?
partially metabolized in liver and excreted through bile
136
T/F some metabolites of tamoxifen have agonist activity?
true
137
What are adverse effects of tamoxifen?
hot flashes, GI, skin rash, potential for endometrial cancer because of decreased estrogen
138
What is the retinal adverse effect of tamoxifen?
crystalline retinopathy and other vision problems, may see deposits in the cornea
139
What is an aromatase reaction responsible for?
extra adrenal synthesis of estrogen, important source of estrogen in postmenopausal women
140
What do aromatase inhibitors do?
decrease production of estrogen, treatment of breast cancer
141
What was the first developed aromatase inhibitor?
aminoglutethimide
142
What is aminoglutethimide normally taken with?
hydrocortisone
143
What are anastrozole and letrozole?
nonsteroidal but more selective and potent aromatase inhibitors-- does not need hydrocortisone supplementation and does not predispose to endometrial cancer
144
What is exemestane?
steroidal inhibitor of aromatase
145
What are the pharmacokinetics of aromatase inhibitors?
well absorbed orally, p450 metabolism, urine excretion
146
What are leuprolide and goserelin?
analogs of gonadotrophin releasing hormone, act as agonists
147
What is the MOA of leuprolide and goserelin?
binding to receptor causes desensitization and a decrease in FSH and LH so androgen and estrogen synthesis is reduced
148
What are leuprolide and goserelin used for?
prostate cancer and advanced breast cancer
149
What are two names for estrogens?
ethinyl estradiol and diethylstilbestrol
150
What is estrogen used for?
treatment of prostate cancer
151
What is the MOA of estrogen use?
blocks production of LH and decrease synthesis of androgens in the testis
152
What are the adverse effects of estrogens?
thromboemboli, MI, stroke, hypercalcemia, gynecomastia and impotence
153
What are flutamide, nilutamide, and bicalutamide?
nonsteroidal antiandrogens
154
What are nonsteroidal antiandrogens (ex: flutamide) used for?
treatment of prostate cancer
155
What is the MOA of nonsteroidal antiandrogens?
compete with natural hormone for androgen receptor, prevent translocation of hormone into nucleus
156
What is the pharmacokinetics of nonsteroidal antiandrogens?
flutamide, nilutamide and bicalutamide, oral administration, kidney excretion
157
What is an adverse effect of nilutamide?
visual problems
158
What are monoclonal antibodies?
antibodies produced by one type of immune cell and all identical clones
159
What is an advantage of monoclonal antibodies?
can create an antibody that can bind to any substance
160
What is a good target for a monoclonal antibody?
cancer cell antigens
161
How is the monoclonal Ab hybrid cell formed?
mice b lymphocytes fused with a tumor cell and then cloned to produce antibodies for a single antigen type
162
How are monoclonal antibodies administered?
injection, cannot be oral because protein structure will break down
163
What is the MOA of monoclonal antibodies?
bind to cancer specific antigens and induce an immunological response like apoptosis, growth inhibition, or interferes with cellular function OR cell is modified to deliver toxin or other active molecule
164
What was the mAb approved to treat cancer?
rituximab
165
What does rituximab treat?
lymphomas and leukemias
166
What is the MOA of rituximab?
binds to site on B lymphocyte and recruits immune effector functions to induce cell mediated cytotoxicity
167
What is the administration of rituximab?
IV infusion
168
What does trastuzumab treat?
attaches to breast cancer-specific receptor and cells undergo G1 arrest and reduction of proliferation (reduces rate of relapse by 50% during first year.
169
What is bevacizumab?
antiangiogenesis agent
170
What is the MOA of bevacizumab?
attaches to a stops vascular endothelial growth factor from stimulating the formation of new blood vessels which decreases oxygen supply to tumor cells
171
What is bevacizumab used to treat?
retinal neovascular diseases like diabetic ret, choroidal neo-vascularization etc (avastin)
172
What is the MOA of platinum coordination complexes?
similar to alkylating agents, bind guanine and cross link DNA
173
What are the pharmacokinetic considerations of platinum coordination complexes?
IV administration, little CSF penetration, renal excretion
174
What are the adverse effects of cisplatin?
sever vomiting, nephrotoxicity, and ototoxicity
175
What are the adverse effects of carboplatin and oxaliplatin?
mild nausea and myelosuppression
176
What is interferon alpha?
primarily leukocytic
177
What is interferon beta?
produced by connective tissue fibroblasts
178
What is interferon gamma?
produced by t lymphocytes
179
What interferons are used to treat neoplastic disease?
alpha 2a and 2b
180
What is the MOA of interferons?
binding of interferon produces complex intracellular reactions that increase inflammation and decrease growth (enzyme synthesis, suppression of cell proliferation, activation of macrophages, increased cytotoxicity of lymphocytes)
181
What are the pharmacokinetics of interferons?
IM or subc injection (or IV form of 2b), minimal liver metabolism, and excretion by kidneys
