Cancer Chemotherapy Flashcards
1
Q
Most common types of cancer?
A
Breast, prostate, lung, colon, melanoma, lymphoma
2
Q
Most common lung cancer deaths?
A
Lung, colon, pancreas, breast, prostate, liver
3
Q
What is cancer?
A
Disease caused by accumulated mutations (nucleotide substitutions that change amino acid sequence and subsequent protein structure/function)
4
Q
Progression from mutation to cancer?
A
Nucleotide mutation/substitution –> changes nucleotide sequence –> amino acids sequence changes –> protein structure & function could change –> altered cell growth –> cancer may develop
5
Q
Mutations in cancer cells give them growth advantages over normal cells and enable cancer cells to do what?
A
Use body resources better than normal cells to grow, form tumors, and invade other tissues
6
Q
Causes of cancer?
A
DNA susceptible to change (mutation, evolution), exposure to chemicals/radiation promotes mutations
7
Q
Most DNA mutations are harmless and cause what?
A
Immediate cell death and no harm to pts
8
Q
Mutations that occur in which parts of DNA can lead to altered cell growth/cause cancer?
A
Tumor suppressor genes or oncogenes
9
Q
What are proto-oncogenes?
A
Sections of DNA that encode for genes used to make specific proteins vital to promote cell growth (kinases, cell surface R’s, regulators of apoptosis)
10
Q
Mutations of proto-oncogenes cause what?
A
Oncogenes that overstimulate cells to grow/can lead to development of highly abnormal cell growth and development of cancer
11
Q
Mutations in which parts of DNA do not lead to cancer?
A
Filler sequences or genes not related to growth
12
Q
What are tumor suppressor genes?
A
Special genes in DNA for proteins which regulate cell growth (serve as mechanism to prevent over stimulating cell growth)
13
Q
Mutations in tumor suppressor genes remove what?
A
Regulation of cell growth and may lead to excessive cell growth/development of cancer
14
Q
Difference between mutation of proto-oncogenes and tumor suppressor genes?
A
Proto-ocogenes: overstimulation of cells to grow
Tumor suppressor genes: No limits/regulation of cell growth
15
Q
Solid tumors affect what?
A
Organs and other solid tissues
16
Q
What are solid tumors are specified by what?
A
Origin of cell type: squamous cell carcinoma, adenocarcinoma, sarcoma, etc.
17
Q
Hematologic malignancies affect what?
A
Blood cells (leukemia, lymphoma, hodgkin disease, myeloma)
18
Q
What is a primary tumor?
A
Original mass of cancer cells of a solid tumor in a body organ
19
Q
Metastasis could be as individual cells or what?
A
New tumor sites
20
Q
Stages used to classify solid tumors?
A
I-IV
21
Q
Stages used to classify hematologic malignancies?
A
I-IV or something else, unique staging methods
22
Q
Localized therapies for cancer?
A
Surgery, radiation
23
Q
Systemic therapies for cancer?
A
Chemotherapy: traditional, monoclonal antibodies, targeting agents
24
Q
Immunomodulation therapy for cancer?
A
Stem cell (bone marrow) transplant, immunosuppressive, immunotherapy, or immunostimulatory agents, CAR-T cell therapy
25
Surgery goals are dependent upon what?
Size, location, type of tumor
26
Can surgery be used for hematologic cancers?
No
27
Is surgery usually used along with other therapy or alone?
With other therapy
28
Is radiation usually used along with other therapy or alone?
May be used alone or with surgery and/or chemo
29
What does radiation involve?
Exposing the patient to ionizing radiation using high energy photon beams
30
Radiation is similar to energy used in x-rays, but with what?
Higher amounts, longer duration, and repeated doses
31
Typical sources of radiation therapy?
External beam using cobalt or cesium
32
Radioactive energy effects on the body?
Electrically charged particles destroy cancer cells and stop them from growing, but may also cause damage to neighboring tissues
33
What does chemo involve?
Use of drugs with various mechanisms of action that disrupt cancer cell function
34
How is chemo administered?
Typically IV or PO
35
Exposing chemo drugs to both cancerous and normal cells results in what?
Significant side effects
36
Do cancer cells follow the cell cycle like normal cells?
Yes, interruption of this cycle can slow/stop tumor growth
37
Based on knowing that cells need certain molecules to grow, scientists synthesized what to block growth pathways of cancer cells?
false analogs (aka antagonists) of vitamins like folic acid
38
Traditional chemotherapy typically targets which mechanics of cell division?
DNA, RNA, DNA polymerase, topoisomerases, spindle fiber formation, etc.
39
Examples of traditional chemo?
Cyclophosphamide, Vincristine, Doxorubicin, Etoposide, Cisplatin, Methotrexate, Paclitaxel, Fluorouracil, etc.
40
What do newer chemo drugs target?
Specific proteins (enzymes, receptors, ligands) required for various cell functions such as growth or apoptosis but are mutated in some way
41
What are newer chemo drugs based on?
Identifying mutated proto-oncogenes and tumor suppressor genes
42
Targeted chemo drug classes?
Tyrosine kinase inhibitors (TKIs), Conjugated monoclonal antibodies, Monoclonal antibodies, Immune checkpoint inhibitors
43
Mechanism of action method for chemo?
Various cancer susceptible to drugs w/ differing MOAs --> giving combos of drugs takes advantage of multiple MOAs to kill cancer cells in different ways
44
What are the principles of identifying drug combos with chemo?
-Efficacy (each drug in a regimen needs anticancer activity when used alone)
-Toxicity (select drugs to minimize overlap of toxicities)
-Optimum scheduling (each drug given in convenient intervals to maximize activity)
-MOA (differing MOAs help overwhelm cells ability to develop resistance)
45
Timing (relative to local tx) and intent importance in chemo?
Local therapy (surgery, radiation) used as primary tx
--> neoadjuvant vs adjuvant chemo
46
What is neoadjuvant chemo?
used before local therapy to reduce tumor/improve local tx success
47
What is adjuvant chemo?
used after to improve long term effect/eliminate remaining undetected cancer cells
48
Is chemo dose dependent?
Typically, yes
(higher doses kill more cells)
49
Higher doses of chemo kill more cells, yet cause more what?
Side effects
50
What helps determine the "safe doses" of meds for chemo in regards to side effects?
Dose limiting toxicities of chemo
51
What is log cell kill kinetics?
A given treatment will kill a constant fraction of cells & subsequent doses reduce cancer burden proportionally over time
*explains why chemo is given as repeated doses over time & not just one dose
52
What is dose density?
Amount of drug/unit of time
-->giving repeated doses of multiple chemo agents over period of time aka chemo cycles (give same drgs once q1-4wks)
53
Regular exposure to chemo (dose density) provides what?
A wave-like approach to killing cancer cells over time
*percentage killed each time pt gets dose of chemo aka log cell kinetics
*time between doses limits side effects/allows body to recover before next dose
54
Maintaining dose density (avoiding pauses and delays or dose redcutions) is what?
Desired, but not always possible
55
What does the term "cure" refer to?
A sustained/prolonged cancer free period (usually 5 years)
56
What does the term "control" refer to?
Reduce cancer burden, prevent extension of cancer, extend survival (cure unlikely)
57
What does the term "palliation" refer to?
Reduce sx, improve quality of life, prolong survival (cure not likely)
58
What does the term "Remission/complete response (CR)" refer to?
Unable to detect presence of cancer
59
What does the term "partial response (PR)" refer to?
Reduction of tumor burden but cancer still present
60
What does the term "stable response" refer to?
Tumor still present but has not grown or shrunk
61
What does the term "treatment failure/progressive disease (PD)" refer to?
Cancer continues to grow despite tx
62
Goal of cancer as chronic disease?
Improve/maintain quality of life and extend survival with drugs to control cancer but nor necessarily cure it
63
Cancer as chronic disease tx avoids what? What does this lead to?
Need to provide overly aggressive/toxic drugs, leads to larger population of patients living w/ cancer w/ different needs
64
Why is cancer as chronic disease tx not used in all types of CA?
As cure is still possible in many situations
65
How to determine response cancer tx?
PE, Radiographs (XR, CT, MRI, PET), Tumor markers (measure conc. of proteins in blood indicating presence of CA/response to tx), Bx/blood tests for presence of cancer cells
66
What terms are used to describe cancers that have not responded to tx?
Refractory or resistant
67
What can more mutations within cancer cells (chemo resistance) result in?
Blocking chemo actions, blocking uptake of chemo into cells, facilitation of excessive transport of drugs back out of cells
68
Other reasons chemo would have lack of effect?
Drug interactions, food interactions, poor adherence
69
How can drug interactions lead to lack of effect of chemo?
(between chemo and non-chemo drugs) can increase metabolism /decrease chemo conc. in patients body
70
Reasons for food interactions leading to lack of effect of chemo?
Specific directions may not be communicated (take w/ or w/o food)
71
Reasons for poor adherence leading to lack of effect of chemo?
Missed clinic appts, missing refills on rx, don't take meds as prescribed
72
Salvage treatment option if primary tx is unsuccessful?
Using combos of other chemo drugs (2nd line, 3rd line, 4th line)
73
Stem cell transplant (bone marrow) treatment option if primary tx is unsuccessful?
Autologous SCT: high dose chemo followed by re-infusion of pt's stem cells
Allogenic SCT: chemo + immune modulation + infusion of donor stem cells
74
Other treatment options if primary tx is unsuccessful?
CAR-T cell therapy or investigational therapies (clinical trials)
75
Older chemo agents use various mechanisms to block what?
Cell division w/ limited discrimination between cancer and normal cells
76
Newer chemo agents target specific functions of cancer cells yet still have what?
Significant side effects (some are serious but rare)
77
What functions can be targets of chemo?
DNA/RNA components, Topoisomerases, Mechanics of division (spindle fibers), Enzymes required for making nucleotides (thymide synthase, dihydrofolate reductase), DNA polymerase, Ribonucleotide reductase, Tyrosine kinases, GF receptors
78
MOA of alkylating agents?
Group of molecules that transfer alkyl group to other molecules and disrupts cancer DNA structure by altering molecular interactions/prevents use of DNA as blueprint for cell division
79
What groups of DNA do alkylating agents target?
sulfydryl, amino, hydroxyl, carboxyl, phosphate groups of DNA
80
Are alkylating agents cell cycle specific?
NO, cell cycle non-specific
81
Examples of alkylating agents?
Carmustine, Lomustine, Mechlorethamine, Melphalan, Thiotepa, Procarbazine, Chlorambucil, Cyclophosphamide, Bendamustine, Temozolomide, Dacarbazine
82
Members of the alkylating agents vary by what?
Structure and family, but have same general MOA
83
Cyclophosphamide (alkylating agent) is used in combo regimens for which cancers?
Breast, leukemia, lymphoma, myeloma, etc.
84
Melphalan (alkylating agent) is used in combo regimens for which cancer?
Myeloma
85
Procarbazine (alkylating agent) is used in combo regimens for which cancer?
Lymphoma
86
Common adverse effects of alkylating agents?
Myelosuppression, Mucositis, Sterility (usually temporary but can be prolonged), N/V, tissue damage following extravasation, risk of secondary malignancy
87
Examples of platinum analogs?
Cisplatin, Carboplatin, Oxaliplatin "-platin"
88
MOA of platinum analogs?
Similar to alkylating agents by binding DNA/forming intra- and inter- crosslinks, also bind to cytoplasmic and nuclear proteins required for cell function
89
Cisplatin and Carboplatin (platinum analogs) are used for which cancers?
Lung, esophagus, testicular, ovary, head & neck, bladder
90
Oxaliplatin (platinum analog) is used for what cancers?
Colorectal, esophageal, pancreatic
91
Adverse effects of Cisplatin (platinum analog)?
Renal toxicity (inc. serum Cr, electrolyte wasting: K, Mg), anemia, N/V, ototoxicity
92
Adverse effects of Carboplatin (platinum analog)?
Avoids major toxicities of cisplatin but causes myelosuppression
93
Adverse effects of Oxaliplatin (platinum analog)?
Neurotoxicity (peripheral neuropathy), myelosuppression, diarrhea
94
What are false analogs (antimetabolites)?
Molecules from nature or lab that substitute for actual components of metabolic processes based on similar (but slightly different) structure
95
General MOA of false analogs (antimetabolites)?
Involve themselves like the actual molecule and inhibit normal cell processes that produce component of DNA (sometimes based on structure of vitamins required for enzymatic activity)
96
Many early chemo drugs were of which class?
Antimetabolites
97
Examples of antimetabolites?
Methotrexate, Capecitabine, 5-Fluorouracil, Cytarabine, Gemcitabine, Fludarabine, 6-Mercaptupurine
98
MOA of Methotrexate (antimetabolite)?
Inhibits DHFR (converts one form of folic acid to another, blocks purine synthesis), also inhibits TS
99
MOA of Capecitabine and 5-FU (antimetabolite)?
Inhibits TS, blocks incorporation of FUTP into RNA and dFUTP into DNA (blocking formation of RNA and DNA)
100
MOA of Cytarabine (antimetabolite)?
Mimics cytidine and inhibits DNA polymerase and DNA repair, prevents DNA chain elongation
101
MOA of Gemcitabine (antimetabolite)?
Inhibits ribonucleotide reductase, preventing production of deoxytriphosphates for DNA synthesis, inhibits DNA polymerase blocking DNA synthesis and repair
102
MOA of Fludarabine (antimetabolite)?
Inhibits DNA polymerase that blocks DNA synthesis and repair, inhibits ribonucleotide reductase preventing production of deoxytriphosphates for DNA synthesis
103
MOA of 6-MP (antimetabolite)?
Inhibits multiple enzymes that synthesize purine nucleotides
104
Methotrexate (antimetabolite) is used for which cancers?
Leukemia, lymphoma, breast, RA
105
Pemetrexed (antimetabolite) is used for which cancer?
Lung
106
Capecitabine (antimetabolite) is used for which cancer?
Breast
107
5-FU (antimetabolite) is used for which cancers?
Colorectal, esophageal, breast, etc.
108
Cytarabine (antimetabolite) is used for which cancers?
Leukemia, lymphoma
109
Gemcitabine (antimetabolite) is used for which cancers?
Pancreas, bladder, breast, lung, ovarian
110
Which special antimetabolite has no anticancer action?
Leucovorin
111
What is Leucovorin?
Reduced form of folic acid that mimics action of engogenous tetrahydrofolate
112
What is Leucovorin used for?
-Decreases methotrexate toxicity by rescuing normal cells (bypasses inhibition of dihydrofolate reductase/DHFR by methotrexate)
-Increases 5-FU activity against colon CA (enhances binding of 5-FU to thymidylate synthase/TS)
113
Adverse effect of Methotrexate (antimetabolite)?
Mucositis, diarrhea, myelosuppression
114
Adverse effect of Capecitabine (antimetabolite)?
Diarrhea, palmar-plantar-erythrodyesthesia (PPE), myelosuppression, N/V
115
How to tx PPE from Capecitabine, Pemetrexed (antimetabolite)?
Dexamethasone
116
Adverse effect of 5-FU (antimetabolite)?
Mucositis, diarrhea, myelosuppression
117
Adverse effect of Cytarabine (antimetabolite)?
Myelosuppression, pulmonary toxicity*, acral erythema, N/V, cerebellar toxicity, ocular toxicity
118
Adverse effect of Gemcitabine (antimetabolite)?
N/V, diarrhea, myelosuppression
119
Adverse effect of Pemetrexed (antimetabolite)?
Myelosuppression, rash, mucositis, diarrhea, PPE
120
How to reduce adverse effects of Pemetrexed?
Vitamin B12 & folic acid supplementation
121
Which chemo agents are derived from natural products?
Alkaloids (original molecules extracted from plants), Antitumor abx (derived from micro-organisms like bacteria/fungi)
122
Which family of alkaloids are derived from periwinkle plants?
Vinca alkaloids
123
Which family of alkaloids are derived from various types of yew trees?
Taxanes
124
Which family of alkaloids are derived from mayapple roots?
Epipodophyllotoxins
125
Which family of alkaloids are derived from the camptotheca acuminata tree?
Camptothecins
126
Examples of vinca alkaloids?
Vincristine, Vinblastine, Vinorelbine
127
Vinca alkaloids MOA?
Inhibit tubulin polymerization required for microtubule assembly and prevent microtubule formation ---> blocks cell division during metaphase ---> cell death
128
Vincristine (vinca alkaloid) is used for what kinds of cancer?
Leukemia, lymphoma, neuroblastoma, Wilm's tumor, rhabdomyosarcoma
129
Vinblastine (vinca alkaloid) is used for what kinds of cancer?
Leukemia, lymphoma, Kaposi's sarcoma, germ cell cancer
130
Vinorelbine (vinca alkaloid) is used for what kinds of cancer?
Lung, breast, ovarian
131
Adverse effects of vinca alkaloids?
Alopecia, neurotoxicity (peripheral neuropathy), constipation, myelosuppression, potent vesicant action upon extravasion
132
What is extravasion?
Tissue damage from leakage of chemo outside of a vein during administration d/t poor needle placement *can be serious injury
133
What kinds of chemo can cause extravasion?
Vinca alkaloids, Anthracyclines
134
S/Sx of extravasion?
Pain, redness, burning, pallor, no blood return, edema, decreased IV flow or flush
135
Examples of taxane alkaloids?
Paclitaxel, Docetaxel, Cabazitaxel, Ixabepilone (not really a taxane but same MOA)
136
Taxane alkaloid MOA?
Promote microtubule formation, preventing spindle fibers from retracting --> blocks completion of cell division and leads to cell death
137
Paclitaxel (taxane alkaloid) is used for what kinds of cancer?
Ovarian, Lung, Prostate, Breast, Head & neck, Esophagus, Bladder
138
Protein-bound paclitaxel (taxane alkaloid) is used for what kinds of cancer?
Breast, lung, pancreatic (sometimes called albumin bound paclitaxel)
139
What is an advantage of protein bound paclitaxel?
Enhances delivery/reduces some toxicity
140
Docetaxel (taxane alkaloid) is used for what kinds of cancer?
Breast, Lung, Head & neck, Gastric, Ovarian, Bladder
141
Cabazitaxel (taxane alkaloid) is used for what kind of cancer?
Prostate
142
Ixabepilone (taxane alkaloid) is used for what kind of cancer?
Breast
143
Adverse effects of taxane alkaloids?
Myelosuppression, hypersensitivity rxn, peripheral neuropathy, fluid retention (docetaxel)
144
Is nanoparticle albumin-bound paclitaxel (nab-paclitaxel) a substitute for original paclitaxel?
No
145
nanoparticle albumin-bound paclitaxel (nab-paclitaxel) is only approved for treatment of which cancers?
Breast, non-small cell lung, pancreatic
146
How does nanoparticle albumin-bound paclitaxel (nab-paclitaxel) have fewer side effects and better delivery?
Avoids use of cremophor found in original paclitaxel which decreases infusion rxns, nano-particle size enhances the delivery to tumor sites, longer half-life, albumin shell escapes recognition by healthy cells
147
Examples of Epipodophyllotoxins (alkaloids)?
Etoposide, Teniposide
148
MOA of Epipodophyllotoxins (alkaloids)?
Inhibit DNA topoisomerase II --> prevents proper unwinding of DNA, resulting in blockade of DNA synthesis and cell division
149
Etoposide is used for which cancers?
Lung, Germ cell, lymphoma, gastric
150
Teniposide is used for which cancer?
Pediatric leukemia
151
Adverse effects of Epipodophyllotoxins (alkaloids)?
Myelosuppression, alopecia, hypotension (if infused too quickly)
152
How are antitumor abx used for cancer?
Compounds produced and used by organisms to compete w/ other organisms for resources, esentially natural cellular toxins, serve as self defense mechanisms that can be chemically isolated/made into anti-cancer agents
153
Examples of antitumor abx?
Anthracyclines/Anthracenedione, Doxorubicin, Daunorubicin, Epirubicin, Idarubicin, Mitoxantrone, Mitomycin, Bleomycin
154
MOA of anthracyclines?
Multiple: inhibit topoisomerase 2, bind to DNA and intercalate DNA strands, generate to free radicals, bind to cell membranes/alter fluid and ion transport
155
Process of DNA intercalation by anthracyclines?
Drug binds to areas on both strands, preventing DNA from being replicated
156
Process of free radical formation by anthracyclines?
Free radicals are very damaging to cells by binding to metabolic products, altering structures, disrupting cellular function
157
Doxorubicin (anthracycline) is used for what types of cancer?
Breast, Myeloma, Leukemia, Lymphoma
158
Daunorubicin & Idarubicin (anthracyclines) are used for what type of cancer?
Leukemia
159
Epirubicin (anthracycline) is used for which types of cancer?
Breast, gastroesophageal
160
Mitoxantrone (anthracycline) is used for which types of cancer?
Leukemia, lymphoma, prostate, MS
160
Adverse effects of anthracyclines?
Myelosuppression, alopecia, N/V, Mucositis, vesicant if extravasated, cardiotoxicity*
161
Mitoxantrone (anthracycline) causes urine to turn what color?
Blue/green
162
Doxo/Dauno/Ida/Epirubicin (anthracycline) causes urine to turn what color?
Red/orange
163
Characteristics of acute cardiotoxicity from anthracyclines?
W/in 24-72 hrs of administration, arrhythmias, pericarditis, myocarditis, usually subclinical
164
Characteristics of chronic cardiotoxicity from anthracyclines?
Dose dependent, delayed by years, results in cardiomyopathy/associated heart failure
165
Cardiotoxicity from anthracyclines can occur at any dose, but risk increases with what?
Cumulative dosing
-1-2% risk for doxorubicin doses <300, 6-20% for doxorubicin doses ~500
166
Risk of cardiotoxicity from anthracycline can be mitigated by what?
Limiting lifetime doses
167
Use of which anthracycline reduces free radical formation in cardiac tissue yet may reduce therapeutic effect of doxorubicin?
Dexrazoxane
168
How can doxorubicin/daunorubicin be formulated to reduce detection/destruction by the immune system?
Liposomes (liposomal anthracyclines)
169
How are liposomal anthracyclines an advantage for avoiding cardiotoxicity, N/V, and myelosuppression?
Larger size reduces exposure to tightly joined tissue of myocardium/GI tract
170
How can liposomal anthracyclines allow for higher os similar efficacy for tumor cells?
Tumors have less tightly joined cells allowing for increased exposure to liposomal chemo
171
Examples of liposomal chemo anthracyclines?
Doxil (liposomal doxorubicin), DaunoXome (liposomal daunorubicin)
172
Bleomycin MOA?
Binds DNA & forms free radicals thqat destroy DNA and prevent DNA replicatin
173
Bleomycin is used for what types of cancer?
Lymphoma, germ cell tumors, head & neck, squamous cell carcinomas
174
Major concern with Bleomycin?
Pulmonary toxicity (pneumonitis, cough, dyspnea)
175
What medication is also used as a sclerosing agent/tx for pleural effusions?
Bleomycin (cancers within or proximate to the lung more likely to cause pleural effusion)
176
RF for pulmonary toxicity with bleomycin?
Age >70, cumulative doses >400u, underlying pulm disease, prior mediastinal radiation, supplemental o2
177
What do tyrosine kinases do?
families of proteins that use ATP to phosphorylate other proteins/control their function (usually enzymatic R's on the surface of cells)
178
What happens when tyrosine kinases are mutated in cancer cells?
Often become overactive and lead to enhanced tumor growth (examples of potential proto-oncogenes and tumor suppressor genes)
179
Examples of TK's in humans?
C-Kit, Epidermal GF Receptor, BCR-ABL (philadelphia chromosome), JAK, Platalet derived GF receptor, human epidermal R
180
TKIs MOA?
Target, bind to, and block activity of various TK's like an antagonist, resulting in inhibition of specific pathways and promotes cancer cell death through apoptosis
*also starting to be used for RA, organ transplant, Crohns, UC
181
Examples of TKIs?
Axitinib, Bosutinib, Gefitinib "end in -inib"
182
Differences between TKIs?
Target different TKs present in different kinds of cancers, differ in binding affinity to their targets (make some more potent/bind with less restriction --> reduces chances for resistance, inc types of TKs they bind to)
183
How does resistance to TKIs develop?
When more mutations occur in the amino acid sequence of the TK that is targeted by the TKI after the drug has been started, which prevent it from binding/make the drug ineffective
184
Axitinib (TKI) is used for what type of cancer?
Renal cell carcinoma
185
Imatinib, dasatinib, nilotinib, bosutinib, ponatinib (TKIs) are used for what type of cancer?
Chronic myelogenous leukemia, Ph+ acute lymphoblastic leukemia
186
Crozptinib and Gefitinib (TKIs) are used for what type of cancer?
Lung
187
Erlotinib (TKI) is used for what type of cancer?
Lung, pancreatic
188
Ibrutinib, Acalabrutinib, Zanubrutinib (TKIs) are used for what type of cancer?
Chronic lymphocytic leukemia, lymphoma
189
Lapatinib (TKI) is used for what type of cancer?
Breast
190
Levatinib (TKI) is used for what type of cancer?
Hepatocellular carcinoma, renal cell, thyroid
191
Pazopanib (TKI) is used for what type of cancer?
Renal cell carcinoma, sarcoma
192
Regorafenib (TKI) is used for what type of cancer?
Colorectal, gastrointestinal stromal tumor, hepatocellular carcinoma
193
Sorafenib and Sunitinib (TKIs) are used for what type of cancer?
Renal cell
194
Vanderanib (TKI) is used for what type of cancer?
Thyroid
195
Adverse effects of TKIs?
Rash, myelosuppression, fatigue, fluid retention, diarrhea, myalgia, congestive HF, QT prolongation, Afib, bleeding, HTN, hepatotoxicity
196
What are TKIs metabolized by that cause them to have many drug interactions?
CYP450
197
Enzyme inhibitors (azole antifungals) can _____ metabolism and _____ side effects of TKIs
decrease metabolism, increase SE
198
Enzyme inducers (phenytoin) can _____ metabolism and _____ effectiveness of TKIs
increase metabolism, decrease effectiveness
199
Reduced bioavailability w/ concomitantuse of stomach acid reducers (H2A, PPIs) can _____ effectiveness of some TKIs
decrease
200
Immunomodulators MOA?
Unclear, may alter tumor necrosis factor TNF levels/increase activity of NK cells, IL-2, interferons/promote apoptosis
201
Immunomodulators are mostly used in combination with ______ to treat what?
Dexamethasone, Multiple myeloma
202
Examples of immunomodulators?
Thalidomide, Lenalidomide (preferred based on efficacy), Pomalidomide
203
Adverse effects of immunomodulators?
Peripheral neuropathy, thromboembolism, fatigue, rash, myelosuppression, dizziness/drowsiness, birth defects (REMS program w/ pt, prescriber, pharmacist)
204
Proteasome inhibitors MOA?
Inhibit complexes of proteins that would otherwise break down unneeded or damaged proteins --> promote activation of signaling pathways that trigger apoptosis
205
Proteasome inhibitors are used for what?
Multiple myeloma
206
Examples of proteasome inhibitors?
Bortezomib (preferred based on efficacy), Carfilzomib, Ixazomib
207
Adverse effects of proteasome inhibitors?
Peripheral neuropathy, neuralgia, rash, N/V/D, myelosuppression, heart failure, activation of Herpes Zoster/Herpes Simplex (requires antiviral prophylaxis), pulmonary toxicity
208
Monoclonal antibodies MOA?
Specifically designed antibodies made using biotechnology to target specific proteins in cancer cells/block their standard function (usually bind to various sites on receptors: EGFR, HER2, CD antigens)
209
Examples of monoclonal antibodies?
Trastuzumab, Cetuximab, Pertuzumab, Panitumumab, Bevacizumab, Alemtuzumab, Rituximab, etc.
210
How are monoclonal antibodies derived in order to reduce risk of adverse effects?
Derived from animals and then humanized
211
Names of monoclonal antibodies are made of what 4 parts?
Prefix (company specific), target substem (tu-tumor, ci-circulatory), source substem (zu-humanized, xi-humanized/chimeric, mu-mouse), suffix (mab)
212
Possible ways monoclonal antibodies are thought to kill tumor cells?
Block R's required to activate cell functions, bind to free protein ligands looking to bind to R's, bind to receptors and trigger apoptosis, bind to R's and trigger antibody-dependent cellular toxicity (ADCC)
213
What is Rituximab used for?
CD20+ lymphoma
214
What is Trastuzumab used for?
Her2/neu overexpressing breast cancer
215
What is Cetuximab used for?
Colorectal CA, head and neck CA, lung CA
216
What is Panitumumab used for?
Colorectal CA
217
What is Bevacizumab used for?
Colorectal, breast, lung, and renal cell cancers
218
Adverse effects of monoclonal antibodies?
Infusion rxns (premedicate w/ acetaminophen, diphenhydramine +/- dexamethasone)
219
Drug specific reactions to Bevacizumab?
Arterial thromboembolic events, delayed wound healing, gastrointestinal perf
220
Drug specific reactions to Trastuzumab?
Heart failure
221
Drug specific reactions to Panitumumab/Cetuximab?
Interstitial lung disease, hypomagnesemia
222
What are conjugated monoclonal antibodies?
Cytotoxic molecules or radioactive particles attached to monoclonal antibodies serving as delivery vehicles to cancer cells
223
Examples of conjugated monoclonal antibodies?
fam-trastuzumab deruxetan, ado-trastuzumab emtansine, gemtuzumab ozogamicin, inotuzumab ozogamicin, ibritumomab tiuxetan
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What are immune checkpoint inhibitors?
Some tumors evade the immune system using surface proteins (programmed death ligand: PD-L1 and PD-L2) that interact with PD-1 R's and inactivate cancer destroying T-cells
--> Nivolumab and Prmbrolizumab (monoclonal abs) target PD-1 R on T-cells/block interaction w/ PD-L1 and PD-L2 that prevent inactivation of cancer-destroying T-cells allowing for an antitumor response
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Examples of checkpoint inhibitors?
Atezolizumab, Avelumab, Durvalumab, Ipilimumab, Nivolumab, Pembrolizumab
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Since checkpoint inhibitor agents only work if the cancer cells are positive for target checkpoint protein (ligand), what must be done?
Testing on the tumor to be able to determine the presence/level of checkpoint proteins
*helps identify patients that will best respond to the agents/individualize cancer therapy
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Adverse effects of checkpoint inhibitors?
Pneumonitis, hepatitis, colitis, endocrinopathies (thyroid, adrenal, pituitary d/o, diabetes), nephritis, rash, infections, infusion rxns
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What is asparaginase?
Enzyme antineoplastic agent that breaks down asparagine to aspartate
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Which cells are unable to make asparagine?
Lymphocytic leukemia (but normal cells can)
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Administering asparaginase can break down available asparagine and do what to lymphocytic leukemia cells?
Deprive them of the necessary amino acid, leading to cell stress/apoptosis
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Forms of asparaginase?
E. coli asparaginase (Elspar)** MC used, PEG-aspargase (Oncaspar) --> long acting/bound to polyethylene glycol molecule, Erwinia asparaginase (made from Erwina yeast, use in pts with hypersensitivity rxn to E.coli)
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Asparaginase can be used in combo with other drugs to treat what?
Acute lymphoblastic leukemia (ALL)
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Adverse effects of asparaginase?
Hypersensitivity (fever, chills, N/V, rash, urticaria, hypotension, dyspnea), clotting/bleeding d/o, pancreatitis, neurologic toxicity
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What is CAR T cell immunotherapy (CAR-T)?
Adoptive cell therapy that is a complex preparation process performed by a manufacturer
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CAR-T process?
T cells harvested from pt --> genetically engineered using neutralized virus --> infects T cells w/ gene that increases production of chimeric antigen R's --> engineered T-cells expanded in vitro --> re-infused into pt --> CARs enhance binding of T-cells to CD19 antigens on leukemia/lymphoma cells/kill them
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CAR-T products available?
Yescarta, Kymriah, Breyanzi, Tecartus, Abecma, Carvykti
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Indications for Yescarta?
Adult pts w/ R/R large B-cell lymphoma after 2+ lines of systemic tx
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Indications fotr Kymriah?
Patients up to 25 with R/R B-cell, ALL adults w/ R/R B-cell lymphoma or follicular lymphoma after 2+ lines of tx
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Indications for Breyanzi?
Adult patients w R/R large B-cell lumphoma after 2+ lines of systemic tx
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Indications for Tecartus?
Adults with mantle cell lymphoma or all following disease progression
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Indications for Abecma and Carvykti?
Adults w/ R/R multiple myeloma after 4+ lines of tx
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How is CART tx given?
Single infusion fgenerally after other chemo
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How to prep for possible infusion rxn with CART?
Pre medicate w/ acetaminophen and H1A
**Do not use corticosteroids unless life threatening situation
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What is likely with CART?
Hypogammaglobulinemia and prolonged cytopenias
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BBW for risk/potentially fatal for CART tx?
Cytokine rlease syndrome, neuro toxicity, hemophagic lymphoshistocytosis/macrophage activation syndrome, prolonged and recurrent cytopenia
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What is cytokine release syndrome w CARTS?
Fever, hypotension, hypoxia, arrhythmias, cardiac arrest, cardiac failure, renal insufficiency, etc.
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How to manage cytokine release syndrome w CARTS?
Monitor for at least 7 days as inpatients and at least 4wks after infusion for rxn
If indicated: supportive therapy with tocilizumab +/- corticosteroids
*only give corticosteroids if life threatening (will kill re-engineered cells/negate the tx)
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What kind of neurotoxicity with CARTS?
Encephalopathy, headache, delirium, anxiety, dizziness, tremor, peripheral neuropathy, seizures
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How to manage neurotoxicity with CARTS?
Monitor for at least 4wks after infusion, recommend patients not drive, do hazardous activities, operate machinery for at least 8 wks after infusion
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Goal of phase I clinical trials for chemo?
Assess safety (dose ranges, schedule, efficacy) ~10-20 pts who have not responded to other tx, test in multiple types of CA
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Goal of phase II clinical trials for chemo?
Assess efficacy (safety, dosing) longer trial w/ more pts (20-40), focus on effect in pts w/ specific cancers who have not responded to other tx
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Goal of phase III clinical trials for chemo?
Assess efficacy compared to standard tc (RCT) and safety (larger than phase II) focusing on stages of specific diseases which approval will be sought
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Genetic factors for selecting treatment?
Studies identified specific agents/regimens that are more active in patients w/ specific mutations
*PCR tests at time of dx to identify mutations/target tx
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Targeted treatment for patients with BRAF V600E mutation?
Vemurafenib, Dabrafenib, Encorafenib
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Targeted treatment for patients with MEK (BRAF V600K) mutation?
Trametinib, Cobimetinib, Binimetinib
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Targeted treatment for patients with IDH1 mutation?
Ivosidenib
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Targeted treatment for patients with IDH2 mutation?
Enasidenib
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Targeted treatment for patients with MEK HER2 mutation?
Trastuzumab
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Targeted treatment for patients with PH mutation?
Imatinib, Dasatinib
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What are the most common secondary cancers?
Acute leukemia or lymphoma
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Are secondary malignancies harder or easier to treat than primary cancers?
harder
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What are secondary malignancies most commonly associated with?
Alkylating agents and etoposide
