Treatment of Cancer Flashcards
1
Q
4 phases of cell cycle?
A
G1 phase: RNA and protein synthesis, cell growth, DNA repair
S phase: DNA completely replicated
G2 phase: additional synthesis of RNA, protein and specialized DNA
M phase: mitosis
- resting phase: cells don’t engage in synthetic activities
- growth fraction: proportion of cells in tumor actively involved in cell division
- generation time: length of cell cycle
2
Q
Mode of action of Chemo?
A
- cell cycle specific:
kills in specific phase of cell cycle, most useful in tumors with large proportion of actively dividing cells - cell cycle nonspecific:
kills in all phases, useful in tumors with low growth index
3
Q
Chemotherapies that are specific to S phase?
A
- antimetabolites
- antifolates
- antipyrimidines
- antipurines
4
Q
Chemotherapies that are specific to G1?
A
- Asparaginase
- Actinomycin D
5
Q
Chemotherapies that are specific to G0?
A
- nitrosoureas
6
Q
Chemotherapies that are specific to mitosis?
A
- vinca alkaloids
7
Q
Chemotherapies that are specific to G2?
A
- bleomycin
8
Q
Chemotherapies that are phase nonspecific?
A
- alkylating agents
- antitumor antibiotics
- cisplatin
9
Q
Diff tx modalities for cancer?
A
- surgery:
definitive
staging
palliative - systemic chemo:
IV vs oral
neoadjuvant vs adjuvant - radiation:
definitive
salvage
palliative
10
Q
Surgery - diff b/t definitive and palliative?
A
- surgery may or may not be first step in cancer care (early stage vs mets)
- definitive:
tx plan that has been chosen as the best one for the pt after all choices have been considered - palliative:
relieving or soothing the sxs of a disease w/o producing a cure
11
Q
Diff means of admin of chemo?
A
- types of cancer tx using drugs to kill the cancer cells
- admin:
IV
injection
intrperitoneal
orally
topically (efudex)
12
Q
Classes of chemo drugs?
A
- alkylating agents
- antimetabolites
- mitotic inhibitors
- anthracyclines
- topoisomerase inhibitors
- miscellaneous
13
Q
MOA of alkylating agents? What phase of the cell cycle does it work on? What cancers is it used for?
A
- one of the first class of drugs discovered of chemo agents
- MOA: directly damages DNA to keep cell from reproducing
- works in all phases of cell cycle
- used to tx: leukemia, lymphoma, hodgkin’s, MM, sarcoma, lung, breast and ovary
14
Q
Primary toxicities of alkylating agents?
A
- nausea
- vomiting
- myelosuppression
- alopecia
15
Q
Classes of alkylating agents?
A
- nitrogen mustards
- platinum analogs
- tiazenes
- misc.
16
Q
Types of nitrogen mustards (alkylating agents)? MC one?
A
- mechlorethamine (nitrogen mustard)
- ** MC: Cyclophosphamide (cytoxan)
- Ifosfamide (ifex)
17
Q
Main SE of Cyclophosphamide (Cytoxan)? What may this lead to? Soln? Other drug that causes this?
A
hemorrhagic cystitis:
- metabolic products of cytoxan secreted into the urine
- bladder mucosa may become damaged - may shed large segments of bladder mucosa - lead to prolonged hematuria
- may lead to urinary obstruction (due to clots)
- if urine is concentrated may cause severe bladder damage
- Soln: need to increase fluid intake b/f and after infusion and pee frequently
- Ifosfamide (Ifex) may also cause this
18
Q
Types of platinum analogues (alkylating agents)? MC?
A
- Cisplatin (platinol) **MC
- Carboplatin (paraplatin)
- Oxaliplatin (eloxatin)
19
Q
SEs of Cisplatin (platinol)? What is given to protect against these SEs?
A
nephrotoxicity:
- pts must be vigorously hydrated prior, during and after cisplatin admin
- monitor electrolytes and renal fxn: low K, Na, Mg levels can be seen
neurotoxicity:
- peripheral neuropathy: painful parasthesias
- ototoxicity that can lead to deafness
- Amifostine is given IV to protect against nephro/neurotoxicity from Cisplatin
20
Q
What long term damage can be caused from alkylating agents?
A
- Leukemia: b/c these drugs damage DNA they can cause long term damage to bone marrow
- in rare cases can lead to acute leukemia
- risk of leukemia is dose-dependent
- risk of leukemia after getting these agents is highest about 5-10 yrs after tx
21
Q
MOA of antimetabolites? What phase do these drugs effect? Used to tx what cancers?
A
- interfere with DNA and RNA growth by substituting for normal building blocks of RNA and DNA
- Phase: damage cells during S phase when x’somes are being copied
- tx: breast, ovary, and intestinal tract cancer
22
Q
Primary antimetabolite toxicities?
A
- myelosuppression
- N/V
- mucositis
- dermatologic (rash, injection site rxn, dermatitis, pruritus)
23
Q
Classes of antimetabolites?
A
- folate antagonists - methotrexate (MTX, trexall)
- Purine analogs - mercaptopurine (6-MP, Purinethol)
- pyrimidie analogs: efudex (5-FU), Gemcitabine (Gemzar)
24
Q
Toxicities of methotrexate? What is given to help ward off toxic effects?
A
(MTX, Trexall)
- MTX toxicity mainly affects cells with rapid turnover:
bone marrow (myelosuppression), mucosa (mucositis)
- can damage liver and kidney
- Sometimes high dose is needed and Leucovorin (reduced folic acid) is given to reverse toxic effects of MTX otherwise pt may die
- decreased renal clearance: may need prolonged therapy with leucovorin
- effusions: will go into effusions and leak out continuously and expose normal tissue to drug
- Vigorous hydration and bicarb loading prevent crystallization of urine in renal tubules
25
What drugs impair MTX ecretion?
- ASA
- NSAIDs
- amiodarone
- omeprazole
- PCN
- phenytoin
- sulfa compounds
26
MOA of mitotic inhibitors? Work on what phase? Classes?
- plant alkaloids derived from natural products
- MOA: work by altering DNA inside cancer cells to keep them from growing and multiplying
- work by stopping mitosis in M phase of cell cycle but can damage all phases by keeping enzymes from making proteins needed for cell reproduction
- AKA: anti-tumor abx or antimicrotubules
- classes:
- vinca alkaloids: Vinblastine, Vincristine (Oncovin)**, Vinorelbine
- taxanes: paclitaxel (Taxol), docetaxel (taxotere)
- epothiolone: ixabepilone (Ixempra)
- anthracyclines
27
Mitotic inhibitors: toxicities and usage in what cancer tx?
- toxicities: myelosuppression, anaphylactic rxns, **peripheral neuropathy
- used to tx many diff types: breast, lung, myelomas, lymphomas, leukemias
28
MOA and types of Vinca Alkaloids?
- interfere with M phse
- Vinblastine (Velban)
- MC: Vincristine (Oncovin)
- Vinorelbine (Navelbine)
29
SEs of Vincristine (Oncovin)? Most common sx of automonic neuropathy?
- neuropathy: can be caused by all vinca alkaloids but most commonly assoc with Vincristine
- paresthesias in fingers and toes (mild)
- sxs can move distal to proximal and result in sig weakness
- constipation: MC sx of autonomic neuropathy (start on stool softeners at beginning of therapy otherwise may progress to severe stool impaction
30
Class of Anthracyclines?
- Daunorubicin (Cerubidine)
- Doxorubicine (Adriamycin)
- Idarubicin
- Epirubicin
31
SEs of anthracyclines? RFs for this? Most commonly assoc with what anthracycline? How can this be screened for?
Cardiotoxicity: leading to systolic CHF - acute (during admin), subacute (days to months following admin), late (yrs following admin)
- RFs: high cumulative dose (over lifetime), over 70, previous or current chest radiation, cardiac disease
- MC assoc with doxorubicin ( Adriamycin - MC used anthracycline)
- Effects may be irreversible
- Need baseline MUGA scan to calc EF (if greater than 50% proceed, if less than 30% d/c)
- long term f/u and monitoring for development of CHF/cardiomyopathy is warranted
32
MOA of topoisomerase inhibitors, phase they work in, how are they grouped?
- drugs interfere with topoisomerases, which help separate strands of DNA so they can be copied during S phase
- Grouped according to which type of enzyme they affect:
topoisomerase I: Topotecan and Irinotecan (CPT-11)
topoisomerase II:
Etoposide (VP-16)
Teniposide
Mitoxantrone (also acts as anti-tumor abx)
33
Topoisomerase inhibitors:
tx of what cancers?
Toxiciites?
- tx certain leukemias, as well as lung, ovarian, GI, and other cancers
- toxicities: myelosuppression, alopecia, GI toxicity
- Top II inhibitors: can increase the risk of 2nd cancer (AML) - as early as 2-3 yrs after drug is given
34
Misc agents?
- Actinomycin-D
- Bleomycin
- Mitomycin -C
- mitoxantrone (also acts as top II inhibitor)
35
SEs of Bleomycin?
- edema in interphalangeal jts and hardening of skin on palms and soles of feet
- anaphylactic or serum sickness like rxn
- **Pulm fibrosis: can be fatal, watch for cough, dyspnea, infiltrates on x-ray
- Hypotensive rxn:
severe to fatal after first dose in about 1% of pts
36
Other types of cancer drugs other than chemo?
- targeted therapies
- differentiating agents
- hormone therapy
- immunotherapy
37
What are targeted therapies? MOA? When is it used? Most effective against? Examples?
- newer drugs that attack cancer cells more specifically than traditional chemo drugs
- most attack cells with mutant versions of certain genes, or cells that express too many copies of a certain gene
- can be used as part of main tx, or they may be used after tx to keep the cancer under control or keep it from coming back
- Most effective against: non-hodgkins, leukemia, lung and breast cancer
- Imatinib (gleevac)
- Gefitinib (Iressa)
- Sunitinib (Sutent)
- Bortezomib (Velcade)
38
MOA and examples of differentiating agents?
- these drugs act on cancer cells to make them mature into normal cells
- ex:
retinoids, tretinoin (ATRA or atralin - topical)
bexarotene (targretin)
arsenic trioxide (arsenox)
39
Use of hormone therapy? MOA?
- sex hormones
- change the action or production of female or male hormones
- used to slow growth of breast, prostate, and endometrial (uterine) cancers, which normally grow in response to natural sex hormones in the body
- work by making cancer cells unable to use the hormone they need to grow, or by preventing the body from making the hormone
40
Examples of hormone therapy?
- anti-estrogens: fulvestrant, tamoxifen, toremifene
- aromatase inhibitors: anastrozole, exemestane, letrozole
- progestins: megesrol acetate
- estrogens
- anti-androgens: bicalutamide (casodex), flutamide, nilutamide
- Gonadotropin releasing hormone (GnRH) aka LHRH agonists or analogs: Leuprolide, and goserelin
41
Diff types of immunotherapy?
| Most effective against?
- active: stimulate body's own immune system to fight the disease
- passive: doesn't rely on body to attack disease -
immune system components (abs) - created outside body and give to fight cancer
Man made monoclonal ABs designed to attach to cancer cells and mark them for destruction by the immune system - checkpt inhibitors: block signals that cancer cells send out telling immune system not to attack, allows immune system to recognize the tumor
- immunotherapies most effective against melanoma, kidney cancer, and lung cancer
42
Examples of active immunotherapy?
- monoclonal ab therapy: rituximab (rituxan) and alemtuzumab (campath)
- non-specific immunotherapies and adjuvants (other substances or cells that boost immune response) - BCG, IL-2, and interferon-alfa
- immunomodulating drugs - thalidomide and lenalidomide (Revlimid)
43
Chemo cycles?
- chemo given at regular intervals called cycles
- a cycle may involve a dose of one or more drugs followed by several days or weeks w/o tx:
this gives normal cells time to recover from drug side effects, sometimes doses may be given a certain number of days in a row or every other day for several days, followed by period of rest, some drugs work best when given continuously over set number of days
- number of cycles given may be decided b/f tx starts, based on type and stage of cancer
- in some cases, number is flexible, and will take into account how the tx affects the cancer and person's overall health
44
Diff chemo regimens?
- adjuvant: set course given to pts with no evidence of disease after surgery or radiation
- neoadjuvant: aims at eradicating micromet disease or reduce inoperable disease
- induction: combo chemo given in high dose to cause remission
- maintenance: also called consolidation, long term, low dose regimen given in remission, maintains remission by inhibiting growth of remaining cancer cells
45
What is radiation therapy?
- ionizing radiation is production of free H+ ions and hydroxyl radicals
- radiation therapy: use of high energy radiation from x-rays, gamma rays, neutrons, protons, etc. to kill cancer cells and shrink tumors
46
How do you determine dose of radiation therapy?
- tumors have individual radiobiologic characteristics:
| unique dose requirements for tx, determined by multiple biologic studies done over time
47
Toxicity of skin radiation?
- erythema: onset 4-14 days
peak: 4-5 wks
resolves: 2-6 wks after completion
- dry desquamation: typicall 5-6 wks, earlier w/ accelerated RT or concurrent chemo, resolves 3-4 wks after completion
- moist desquamation: following 40-50 Gy, trauma/excess friction, bolus, chemo
recovery: 2-6 wks after completion
48
Subacute and late toxicities of skin radiation?
- subacute:
hyperpigmentation:
as early as 2-3 wks, usually resolves 3-12 mos, occasionally chronic
- late:
hypopigmentation in tx field, telangiectasis, fibrosis
49
Toxicity of brain radiation: acute and late?
- acute:
fatigue, hair loss, erythema of skin, desquamation
- late:
cognitive dysfxn, edema, necrosis
50
Toxicity of head/neck radiation: acute and late?
- acute:
mucositis: odynophagia, dehydration, wt loss
taste dysfxn
pain
xerostomia: may lead to dental caries
- late:
permanent xerostomia
soft tissue fibrosis
osteoradionecrosis of mandible
dysphagia
pharyngeal stricture
51
Toxicity of breast radiation?
```
- acute: common and temporary
skin redness (90%)
fatigue (70%)
dry desquamation
moist desquamation
pain
- late: uncommon and permanent
fibrosis (15%)
hyperpigmentation (10%)
cosmetic failure (15%)
rib fracture (less than 0.1%)
```
52
Acute toxicity of lung radiation? Tx of these?
esophagitis:
- mucosal anesthetics (viscous lidocaine)
- agents that coat the surface (suspension or liquid antacids)
- liquid analgesics
```
cough:
- antitussives w/ or w/o codeine
- radiation pneumonitis: bed rest, bronchodilators and corticosteroids
abx not indicated
- skin rxn
- fatigue
```
53
Late toxicity of lung radiation?
- radiation pneumonitis
- pulmonary fibrosis (typically not reversible)
- esophageal stricture
- brachial plexopathy: superior tumors
54
Acute and late toxicites of esophageal radiation?
acute:
- esophagitis
- modest skin tanning: posterior
- fatigue
- wt loss
- diarrhea
- N/V
late:
- esophageal stricure and stenosis (more than 60% of pts)
- perforation:
substernal chest pain, elevated pulse, fever, hemorrhage
- pneumonitis - rare
55
Acute and late toxicities of abdominal radiation of stomach, pancreas and hepatobiliary?
acute:
- dyspepsia: PPI to reduce acid
- anorexia
- nausea: prophylactic zofran prior to tx
- fatigue
late:
- bowel obstruction
- worsening diabetes 2nd to worsening pancreatic fxn
- liver/kidney: usually kept at safe doses, renal failure, HTN
56
Acute and late toxicities of pelvic radiation?
```
acute:
- diarrhea - common: imodium, lomotil
- rectal irritation: rare (pain and bleeding)
- urinary sx:
freq/urgency
dysuria
nocturia
retention
- fatigue
```
```
late:
- persistent urinary sx:
frequency, nocturia, incontinence
- bowel changes: loose stools
- erectile dysfxn
```
57
Acute and late toxicities of anal radiation?
```
acute:
- skin rxns:
dry and/or moist desquamation
- leukopenia
- thrombocytopenia
- proctitis
- diarrhea
- cystitis
```
subacute/late:
- chronic diarrhea
- rectal urgency
- sterility
- impotence
- vaginal dryness
- vaginal fibrosis
- possible decreased testosterone
58
Toxicities of GYN radiation? tx?
- cystitis
- proctitis
- fistula: rectovaginal, vesicovaginal
- vaginal ulceration/necrosis
- vaginal stenosis
- skin rxns (rectal, anal, vulvar):
desquamation: tx with hydration, domeboro soaks, silvadene, and narcotic pain meds
attempt to decrease dose to external genitalia to reduce skin rxns (groin and interglutteal clefts)
59
What is the only systemic side effect of radiation?
- fatigue
60
Degree of damage is dependent on what tx regimen related factors?
- types of radiation used
- total dose admin
- field size/fractionation
61
Late side effects caused by radiation should be a dx of what?
- dx of exclusion
- explore other causes of sxs
- discuss with radiation oncologist who can look at the plan to verify radiation as cause
