Chemotherapy Flashcards
Goals of Chemotherapy
- Cure
- Control (live with, like chronic illness)
- Palliation (prevent suffering)
- Neo-adjuvant treatment (before surgery)
- Adjuvant treatment (after surgery)
- Chemoprevention (hormone)
- Myeloablation (preparation for BMT)
Adjuvant
in addition to
surgery > chemotherapy > radiation
Neo-adjuvant
chemotherapy > surgery > radiation
Concurrent
Surgery > (chemo + radiation)
Fundamental Principles of Chemotherapy
- Cell Killer model
2. Norton-Simon Hypothesis
Cell Killer Model
Skipper 1971
# of cancer cells killed per cycle (1st order kinetics)
Assumes all cells are: actively dividing, constantly treatment sensitive, growing at consistent rate
Limitations: not all actively dividing at same time, cells can grow at different rates
***doesn’t work
Norton-Simon Hypothesis
Gompertzian Tumor growth kinetics 1977 Tumor grow faster when small??? Les time to recover, more likely to destroy -dose-dense regimens -shorter cycles -more side effects (use growth factors)
Chemo Basics
-generally nonspecific (attack all dividing cells)
-Target rapidly dividing cells (cancer & healthy)
-cytotoxic
action during cell cycle
combination therapy = greatest effect
Cytotoxic
cellular poison
Cystostatic
blocks cell replication
cytocidal
apoptosis
Chemotherapeutic agents classification
cell cycle specific, nonspecific
Routes of Administration
Oral IV IM intra-arterial Intrathecal Intraperitoneal Intrapleural
Intrathecal
NEVER VINCRISTINE
Cell Cycle
M, G1, S, G2….
Cell cycle Non-specific Drugs (CCNS)
exert effect within any cell cycle phase
Alkylating, Anti-tumor antibodies, nitrosureas, Hormones
Cell cycle specific drugs (CCS)
Exert effect within specific cell cycle phase
Antimetabolits, mitotic inhibitors (vinca, Taxanes), Topoisomerase I inhibitors, Topoisomerase II inhibitors
Alkylating Agents (CCNS)
- cell cycle nonspecific
- MOA: DNA strand breakage, prevent cell reproduction/replication
- Alkylator classes
Common SE of Alkylating Agents
myeolosuppresion hypersensitivity renal toxicities GI cutaneous toxicities (hand and foot) secondary malignancies
Aklylating Agents CCNS: Platinum compounds
- grouped with alkylating agents bc of mechanism of action
- efficacy highly dependent on renal elimination
- Adequate renal function IMPERATIVE
- establish prior and during treatment (BUN and CREAT)
- less likely to cause secondary malignancies
Antitimor Antibiotics: CCNS
different from those for infectiosn
- MOA: Cell cycle nonspecific, bind with DNA and inhibit synthesis, prevents cell replication
- produced by streptomyes organisms
- Anthracyclines
Antitumor Abx - common SE
Myelosuppression
GI toxicities
Cutaneous toxicities - vesicants (doxorubicin) EMERGENCY
Organ toxicities (cardiotoxic, pulmonary toxic)
Anthracyclines
antitumor antibiotic
has lifetime maximum cumulative dose
too much will affect cardiac function
epipodophyllotoxins
Antitumor antibiotic classification
Topoisomerase II inhibitors
Bleomycin
Antitumor abx CCNS
pulmonary toxicity: fibrosis
fever and chills during and after infusions
lifetime dose limit 400
Doxorubicin
red in color vesicant cardiac toxicity Dexrazoxane (cardioprotectant) given together if possible flare reaction N/V red urine lifetime dose 550mg (reduce if prior irratidation or cotreat with cytoxan)
Nitrosoureas CCNS
cell cycle nonspecific
MOA: break DNA helix, inhibit replication
**crosses BBB (rare), treats brain tumors
highly lipid soluble
treats cancers involving CNS (HL and NHL)
Notrosoureas SE
myelosuppression deyated, severe, and prolonged
GI toxicities: severe N/V, require antiemetics
secondary malignancies such as acute leukemia, bone marrow dysplasia
delayed pulmonary dmage
ex: Carmustine, Lomustine
Carmustine (BCNU)
(Nitrosureas CCNS) myelosuppression - nadir day 14, delayed irritant painful during infusion pulmonary fibrosis
Lomustine
(Nitrosureas CCNS) Myelosuppression, nadir 14-21 given Q6-8 weeks to delay toxicities, time to recover N/V renal and hepatic toxic pulmonary suppression ovarian and sperm suppression
Hormonal Therapy
Anti-estrogen
Anti-Estrogen Aromatase Inhibitor
Lutenizing Hormone-releasing hormone analog
Anti-androgens
Breast tumor tissue tested for:
Estrogen Receptors (ER) Progesteron Receptors (PR) *can use hormonal treatment if responsive
ER/PR positive tumors
50-60% response rate with hormonal therapy
Hormonal treatment: Premenopausal women
ovary = primary source of estrogen
ablation if estrogen source: oophorectomy, ovarian radiation, lutenizing hormone-releasing hormone antagonist,not been shown to benefit women receiving chemo, addition of hormonal agents are more effective
Hormonal Treatment: Postmenopausal women
adrenal gland = primary source of estrogen is the adrenal glands
ablation of estrogen source - administering an aromatase inhibitor
(Br ca hormonal trx) Anti-Estrogen Treatment
Tamoxifen (non-steroidal anti-estrogen)
- oldest and most frequent
- adjuvant therapy and advanced disease treatment
- reducing risk of developing br ca in women at high risk
- agonist or stimulator in endometrial tissue, bone, and lipids results in: inc blood close/endometrial cancer
(Br ca hormonal trx) Anti-Estrogen Aromatase inhibitors (AIs)
- suppress postmenopausal estrogen synthesis
- inhibits peripheral conversaion of androgens to estrogens
- ovarian production of estrogen is NOT affected
- IMPORTANT: AIs are not indicated in premenopausal women
(Br ca hormonal trx) Luteinizing hormone releasing hormon (LHRH) agonists
- synthetic analogs of naturally occurring hormone
- cause initial inc in testosterone levels bc stimulate LH release
- pituitary gland becomes desensitized with continued use, results in significant decrease of estrogens and androgen production
Prostate Cancer Hormonal Therapy
LHRH agonists
Antiandrogens
Prostate hormonal therapy: LHRH
- -synthetic analogs of naturally occurring hormone
- cause initial inc in testosterone levels bc stimulate LH release
- pituitary gland becomes desensitized with continued use, results in significant decrease of estrogens and androgen production
Prostate hormonal therapy: Anti-Androgens
- indicated for males with hormone-responsive metastatic prostate ca.
- alone or in combo with gonadotropin-releasing hormone analog
- bind to androgen receptor
- block the effects of dihydrotestosterone on prostate cancer cells
Side effects of hormonal therapy
Hot flashes
Osteopenia
Management of hot flashes
Dec consumption of caffeine, alcohol and spicy foods
wear cotton
stress reducing activities
exercise
clonidine oral or transdermal patch (not proven)
neuroleptic agents and SSRI
Management of osteopenia
occurs with most hormonal (except tamoxifen and raloxifene)
- assess for family hx of osteoporosis or osteopenia
- assess wt, race and exercise patterns
- testing bone density annually
- advise to avoid alcohol and smoking
- perform weight bearing exercise
- Vit D and calcium supplementation
Side effects of hormonal therapy
Sexual Side effects
–women: vaginal dryness/atrophy (manage with lube)
–men: loss of libido, impotence, difficult topic to address
Cardiovascular effects: arterial lipid accumulation, promotion of blood flow, and vascular elasticity
Cognitive impairements
Management of cardiovascular SE of hormonal therapy
assessing for smoking
hypertension
encourage exercise
checking and annual lipid profile
Antimetabolites CCS
-Analogues of naturally occurring metabolites
MOA:
Antimetabolites CCS Common side effects
Myelosuppresion
GI toxicities
Cutaneous toxicities (mucositis, hand/foot syndrome)
Flourouracil (5FU)
?
Capecitabine
?
Methotrexate
Large dose range
renal failure can occur with large doses
Rescue with Leucovorin = antidote
Mitotic Inhibitors (CCS)
cause neuropathy, may be lifelong - limit amount given
stops mitosis in M phase
can damage cell in G2 and S phases, keeps enzymes from making proteins needed for cell reproduction
Types:
Plant Alkaloids (Taxanes, Vinca alkaloids)
Epthilones
Estramustine
Mitotic Inhibitors: Vinca Alkaloids (CCS)
plant alkaloids MOA: acts late G2 and M phase Ex. Vincristine, Vinblastine, inorelbine SE: myelosuppression, neuropathy, constipation, DEATH IF INTRATHECAL
Mitotic Inhibitors: Taxanes (CCS)
plant alkaloid
MOA: Act in G2 and M phase
Paclitaxel: hypersensitivity, premed with dexamethasone, cimetidine, diphenhydramine, non-PVC bag with filter, perhipheral neuropathy, alopecia
Docetaxel: premed with steroids to reduce fluid retention, nail changes, lacrimation
CCS Plant Alkaloids
CCS: M, G2, S
MOA: mitotic spindle poison, affects microtubule assembly, inhibits mitosis
Common SE: myelosuppression, alopecia, hypersensitivity, Neuropathy, constipation
Categories: Taxanes, Vinca alkaloids, epipodophyllotoxins
Topoisomerase Inhibitors CCS
Cell cycle specific: S, G2 interfere with enzymes (topoisomerases) inhibits unraveling of DNA prevents DNA replication during S and G2 grouped by type of enzyme they affect: ---Topoisomerase I inhib: campothecins ---Topoisomerase II inhib: Epipodophyllotoxins
Topoisomerase I Inhibitors(CCS): Camptothecins
Cell cycle - S phase
MOA:
Irinotecan – cramping, Diarrhea, imodium or atropine, IV K support
Topotecan – diarrhea, alopecia, myelosuppresion
Topo II Inhibitors (CCS): Epipodophyllotoxins
Plant alk.
G2, S,
MOA: induces irreversible blockade of cells, premitiotic, interferw with topo II enzyme rxn
Ex: Etoposide
Factors affecting Response
- combination vs single agent
- combo therapy increases proportion of cells killed at any one time due to heterogeneous cell populations
- reduces drug resistance
- must have proven efficacy as single agents with minimally overlapping organ toxicity
- uses drug synergy to maximize effect
Factors Affecting response: Dose intensity
refers to amount of drug delivered per unit of time (mg/m2/wk)
dose delays or reductions have been shown to compromise survival
receiving less than 85% of planned dose may affect pts outcome
Factors Affecting response: Dose Density
refers to reducing time between doses
give drugs in fractions that are closer together in time
lessen the chance of tumor regrowth between treatments
hematopoietic growth factors are usually required with dose-dense therapy or given prophylactically
Factors Affecting response: Dose intensification
accelerated dose intensity treatment (ie. increasing doses over shorter periods of time)
Factors Affecting response
Tumor burden
Resistance -
- anatomic failure agents unable to prenetrate sites like the brain, testes, or can occur because of inadequate blood supply
-genetic resistance caner cells may have a phenotypic, intrinsic type of drug resistance that arises from spontaneous mutations
+Characteristic: size and location
+physical status of pt
+psychosocial status of pt
+hormone receptor status -antihormonal agents can suppress the growth if tumor grows more rapidly in presence of certain hormones
Mutations
- cancer cells exposed repeatedly to chemotherapy may develop resistance by mutating
- overexpression of MDR-1 gene (multidrug resistance)
- MRD-1 overexpressed = pump overactive ad more chemotherapy is carried out than normal
- Detection of MDR-1 gene product is a predictor of poor prognosis and survival
- other genes: p53, BCL-2 and BAX
Education Assessment
primary language patient understanding barriers to learning learning needs knowledge of planned treatment contact information
Pretreatment: Review of treatment plan
check height/weight BSA calculate dose check lab values know vesicant or irritant properties identify possible side effects and toxicities
Pretreatment Assessment
previous treatment previous cycles, toxicities? medical and surgical treatment allegy hx accurate height and weight BSA lab values performance status tumor type, grade, and stage
Pretreatment Risk assessment
physiologic versus chronologic age
performance/functional status (ability to perform ADLs and be independent)
comprehensive geriatric assessment
Comorbidities (esp. those affecting organs to be stressed by chemotherapy regimen: cardiac, renal, pulmonary, hepatic)
Intra-cycle patient monitoring
common chemo adverse effects and timing acute, delayed and anticipatory CINV mucositis myelosuppression fatigue neuropathy psychosocial distress
Dose Modifications: delay dose
allow pt additional time to recover
may attempt to challenge at same dose after break
Dose modification: Dose reduction
either on time, or after a break
once reduced, new lower dose level is generally permanent
Dose modification: avoid
in cases where the full dose intensity is known to be associated with potential cure, avoid modifications
- early stage breast cancer
- germ cell tumor (testicular, ovarian)
Chemoprotectants
Amifostine
Dexrazoxane
Mesna
Leukovorin
Amifostine
chemoprotectant, reduces renal injury with chemo
Dexrazoxane
cardioprotectant
Mesna
used to decrease bladder irritation (hemorrhagic cystitis) with high dose chemo (ifosfamide)
Leukovorin
used with methotrexate as a rescue
Considerations for the NP
Assessment of patient capacity: ability to tolerate, social support
NP is the “shepherd”
White Blood Cell suppot
Neupogen (shot acting), given until counts recover
Neulasta (long acting) - 24 hrs post chemo
Red blood cell support
Epogen given weekly to every 3 weeks
