20 - Cancer Treatment Flashcards
Adjuvant therapy
systemically administered therapy with cytotoxic drugs, hormones, or biologic response modifiers to kill micro metastases after the primary tumor has been eliminated
Neoadjuvant therapy
treatment given before surgery to reduce tumor and allow better surgical resection
Remission
- complete disappearance of cancer symptoms, typically occurring when the number of cancer cells decrease below 10^9.
- complete clinical remission is not the same as being cured
Cure
to be rendered clinically and pathologically free of disease, and returned to a life expectancy the same as that of a healthy individual of the same age and sex
What are factors that determine treatment modality ?
- Cancer type
- Location and size of tumor
- Extent of disease
- Radiosensitivity or chemrsensitivity
- History of prior therapy
- Concurrent organ dysfunction
- Performance status (overall physical functioning)
- Patients goals/wishes
What are cancer treatment modalities ?
- Surgery
- Radiation therapy
- Chemotherapy (targets any cell that is growing quickly)
- Biological & Targeted Therapy
- Supportive care
What are some of the roles that surgery can play in cancer management?
- Can provide curative Tx for localized mass
- Can be used to reduce the size of the tumor, or debulk it
- Can be used to remove isolated metastatic disease (ex. pulmonary wedge resection)
- Can be used to treat complications such as obstruction, hemorrhage, or perforation
- Can be used to reconstruct anatomic defects to improve function or appearance
How does radiation therapy work?
- Breaks bonds in DNA causing loss of proliferative capacity
- Induces apoptosis
- Plan to deliver tumoricidal dose within limits of tolerance of surrounding normal tissues
- Normal tissues are usually able to recover better than cancer cells
What are some methods of delivery of radiation therapy?
- External beam (tele therapy)
- Internal (brachytherapy)
- High dose rate (HDR) with remote loading
- Low dose rate implanted (temporary or permanent)
ex. prostate seeds
What are some general radiation SE ?
- radiodermatitis
- fatigue
- weight loss d/t anorexia
- myelosuppression (skull, sternum, long bones)
What are some site specific radiation SE ?
depends on structures present in area of radiation Tx (RTx)
What is pulmonary pneumonitis?
can be acute or develop 2-3 months after tx starts
What is pulmonary fibrosis?
occurs after 6-12 months, chronic, not reversible, can be fatal
For pulmonary, what do we need to assess?
cough, fever, hypoxia, exertion dyspnea
Treatment for pulmonary radiation therapy?
- High-dose corticosteroids for acute pneumonitis
- Bronchodilators
- Oxygen (may need home O2 if chronic fibrosis)
- activity modification
- codeine is more effective cough suppressant than OTC
What are some GI side effects of radiation therapy and how can we manage them?
N/V:
- prophylactic anti-emetics before tx
- usually occurs if brain or stomach in tx field, otherwise is mild
Diarrhea:
- Monitor intake/output, assess for dehydration & acidosis if severe
- Non-irritating diet: low-fibre
- Anti-diarrheal medications
How is sexuality/reproductive health affected by radiation therapy?
- Gonads very sensitive to radiation
- Easier to shield testicles from pelvic radiation
- If one ovary spared, may preserve fertility
-Inform pt of expected effect of Tx on fertility
- In Manitoba: Heartland Fertility Clinic offers:
- egg, embryo, sperm cryopreservation
- Patient pays
- They prioritize cancer patient referrals
- If gene radiation may develop dryness, atrophy
- Lubricants, sexual activity/dilator to maintain vaginal patency
-Impotence r/t prostate cancer Tx
What is chemotherapy?
- The use of cytotoxic medications to kill cancer cells
- Goal: reduce and/or eliminate visible and invisible (micro metastases) disease
- Cancer cells can develop resistance to chemo tx
- Most often is SYSTEMIC, therefore systemic side effects
What are some routes of chemo administration?
Most common:
- Oral
- IV (bolus and then continuous infusion)
- Intra-thecal: b/c most chemo doesn’t cross BBB (only certain drugs are ok via this route!)
Less common:
- IM: L-asparaginase
- Intra-cavitary: ex. bladder
- SC: may be used for basal cell skin cancer
What are some principles of chemotherapy?
- Start therapy when tumor burden is low and growth fraction is high
- Use a combination of drugs
- Use a dosing schedule that limits tumor regrowth during host tissue recovery
- Dose to maximum tumor response or toxicity before changing therapy
- Therapeutic benefit must exceed toxicity
What are some principles of combination chemotherapy regimens?
- Drugs are active against the tumor when used alone
- Drugs that have a biochemical basis for suspected synergy
- Drugs that have different MOA
- Drugs that produce toxicity in different organ systems (or in the case of bone marrow toxicity, the toxicity occurs at different times following administration)
- Optimal dose and schedule for the agents are used
Combo Chemo:
R-CHOP
- Rituximab
- Cyclophosphamide
- Hydroxydaunorubicin (doxorubicin)
- Oncovin (vincristine)
- Prednisone
Combo Chemo:
ESHAP
- EtopoSide
- metHylprednisolone
- Ara-C (cytarabine)
- cisPlatinum
Combo Chemo:
FEC
- Flurouracil
- Epirubicin
- Cyclophosphamide
Combo Chemo:
FolFOX
- Folinic acid (leucovorin)
- 5-Flurouracil
- OXalipatin
Doses of chemo are carefully calculated according to ?
body surface area
*height and weight on chemo patient must be exact & measured
What are some classifications of chemo agents?
- Alkylating agents
- Antimetabolites
- Antitumor antibiotics
- Plant alkaloids
- Nitrosureas
- Corticosteroids
- Hormones
- Miscellaneous
Describe alkylating agents
- contain highly reactive ions on their chemical structure
- in some cases they must be activated/converted in the body to create the highly reactive, positively charged ions
- these positively charged ions react with electron-rich portions of the cell (proteins and DNA) to form strong chemical bonds thus leading to inhibition of DNA synthesis
- cell cycle non-specific
What is an example of alkylating agent?
Cisplatin
Describe Cisplatin
- Very important agent u sed for the Tx of testicular cancer, lung cancer, ovarian cancer, breast cancer
- Considered one of the most emetogenic antineoplastics currently used
- Has a role as radiation sensitizer
- Significant toxicities, including renal, neuropathy, alopecia
- Can display delayed n/v (can use anti-emetics)
- Toxic to kidneys!
- If they already have poor renal function, it will drive them into renal failure
MOA of Cisplatin (alkylating agent)
- Cl ion gets replaced with water
- It goes into nucleus and becomes very highly reactive molecule, attaches to one strand of DNA and then the other and forms a cross-link
Is Cisplatin or Carboplatin better ?
Cisplatin
Describe plant alkaloids
Derivatives of different types of plants
- Vinca alkaloids
- Taxanes
- Camptothecin
- Epipodophylltoxins
Usually block a particular enzyme or arrest the cell is some step of mitosis or cell division
Cell-cycle specific
Describe Vincristine
- Vinca alkaloid
- Cell-cycle specific-inhibition of microtubule formation
- Peripheral and autonomic neuropathy
- Useful agent for the Tx of non-Hodgkin’s lymphoma
MOA of vincristine (plant alkaloids)
The mitotic spindle consists of helically polymerized tubulin
Vincristine incorporates intself into microtubules and prevents chromosomes from replicating
So it cannot undergo replication anymore
Antimetabolites
- Act by interfering with the metabolic processes of the cell. Interfere with nucleic acid biosynthesis
- Are subdivided into folate antagonists, purine analogues, and pyridine analogues
- As a class tend to bind enzymes responsible for DNA or RNA synthesis
- Additionally may mimic one of the DNA or RNA nucleotides thus halting further replication
- Cell-cycle specific
_____ is an example of an anti-metabolite
flurouracil
Describe Flurouracil (Antimetabolites)
- Most extensively studied and used agent in colorectal cancer
- Similar to the pyrimidine, uracil
- Blocks the enzyme, thymidylate synthase
- pattern of flurouracil toxicity differs between bolus administration and continuous infusion
- Useful as a radiation sensitizer
Describe antitumor antibiotics
- drugs in this class are products of the species of bacteria Streptomyces
- however, their bone marrow toxicity makes them inappropriate for use as antibacterial agents
- anti-tumor antibiotics act by binding to or complexing with DNA and/or RNA, thus inhibiting replication - intercalation
- can also produce single-strand and double-strand DNA breaks
- can generate free radicals that will then seek out electron rich molecules such as DNA, RNA or proteins
- cell-cycle non-specific
An example of antitumor antibiotics ?
- Doxorubicin (Adriamycin)
- Bleomycin
Describe Doxorubicin (Antitumor antibiotic)
- Anthracycline antibiotic with a lifetime cumulative dosage (500-550 mg/m2)
- Most serious dose-limiting side effect is cardiomyopathy
- Extensive use for Tx of breast cancer and lymphomas
- Can produce radiation recall
*Cardiac toxicity is cumulative, need to record every dose they’ve ever gotten
Describe Bleomycin (Antitumor antibiotic)
- Damage DNA and prevent repair
- Dose-limiting toxicity is pulmonary fibrosis
- Active agent for the Tx of lymphomas, testicular cancer
- Development of chills/fever post Tx
- Cell cycle-specific
Acute reactions of chemotherapy ?
- Vomiting - prevent with anti-emetics
- Allergic reactions - some drugs require pre-medication to decrease risk of allergic rx/anaphylaxis
Delayed effects of chemotherapy ?
- Mucositis of varying severity
- Alopecia
- Bone marrow suppression: bleeding d/t decreased platelets
- Fatigue: d/t decreased Hgb and other factors
- Skin changes: dryness, flaking, peeling
- N/V
- Diarrhea
What are some chronic toxicities of chemotherapy ?
- Unique to each medication
- Assess carefully to allow for early identification
- Damage to: heart, kidney, liver, lungs, bone marrow, reproductive
Toxicities to chemo:
Heart
Heart:
ex. anthracyclines - follow with serial MUGA, assess s/sx CHF, d/c meds if LV dysfunction. These meds have maximum lifetime doses even in absence of cardiac dysfunction
Toxicities to chemo:
Kidney
Kidney:
-ex. cisplatin, carboplatin - monitor serum urea/Cr & CrCl (24 hour urine), monitor intake, output
Toxicities to chemo:
Liver
Liver:
-ex. monitor LFTs, jaundice edema
Toxicities to chemo:
Lungs
Lungs:
-ex. bleomycin - follow with serial PFTs, assess respiratory function
Toxicities to chemo:
Bone marrow
Bone marrow:
-most drugs can cause chronic bone marrow failure if used over a prolonged period of time - follow with CBC and bone marrow Bx if signs of bone marrow failure
Toxicities to chemo:
Reproductive
Sterility - depends on drugs & dose, assisted fertility
What are some late effects?
Risk for leukemias and other secondary malignancies:
-Radiation and chemo Tx can induce DNA damage that can lead to new malignancies other than original Dx
Secondary malignancies other than leukemias have been reported:
-Includes breast (esp women who had chest radiation without shielding prior to 1980’s), uterine, thyroid, lung
Secondary malignancies are usually Tx-resistant
What can lower neutrophils cause?
increased chance of infection and can die from infection
What can lower platelets cause?
increased chance of bleeding
List 2 types of hematopoietic therapy
1) Granulocyte Colony-Stimulating Factor (GCSF)
2) Erythropoietin
Describe
1) Granulocyte Colony-Stimulating Factor (GCSF)
-Stimulates production, maturation, regulation, & activation of WBC
-Hastens recovery from bone marrow depression post-chemo
Stimulates stem cell mobilization to periphery for transplant
-Very important part of many protocols - revolutionized cancer care
-Supportive care not cancer Tx
Describe
2) Erythropoietin
- Used more commonly with renal disease than cancer
- Platelet stimulating factors: none on market in Canada
- Transfusions of RBC & platelets are use instead of growth factors
What effect does Bleomycin, Doxorubicin, Mitoxantrone, MTX cause?
Mucositis
What effect does Cytarabine, 5-FU cause?
Mucositis, Diarrhea
What effect does high dose melphalan have?
Esophagitis, stomatitis, diarrhea, and colitis
What effect does high dose Etoposide have?
oropharyngeal mucositis
Describe CINV (chemotherapy-induced nausea and vomiting)
- maximal emetic intensity seen within 24 hours post dose
- distinct second phase seen, occurring on days 2-4 post dose
What are some factors relating to chemotherapy causing CINV ?
- Intrinsic emetogenicity of chemotherapeutic agents
- Dose
- Route of admin
- Rate of infusion
- Repeated cycles of chemotherapy
What are some factors relating to patients causing CINV ?
Patient characteristics:
- Low alcohol consumption (<10 drinks/week)
- Younger age (<50 years)
- Female gender
- History of motion sickness
Cisplatin is a level 5 agent for ______
nausea
List some antinauseants
- Steroids (dexamethasone)
- Dopamine receptor agents (haloperidol, domperidone, metoclopramide)
- Serotonin antagonists (ondansetron, granisetron, dolasetron, palonesotron, tropisetron)
- Benzodiazepines (lorazepam)
- Cannabinoids (abilene, dronabinol)
- Neurokinin-2 blockers (aprepitant)
Describe pulmonary toxicity of antineoplastics
Pulmonary toxicity:
- Rare but often fatal complication of cancer chemotherapy
- Usually a result of inflammation and subsequent formation of scars in the lungs after the administration of certain chemotherapy drugs
- Sometimes referred to as pneumonitis or pulmonary fibrosis
- Dose-limiting toxicity of agents such as bleomycin, busulifan, carmustine
- Concern if patient to receive chest irradiation
List types of toxicities associated with antineoplastics?
- pulmonary toxicity
- peripheral neurotoxicity
- cardiac toxicity
Describe peripheral neurotoxicity of antineoplastics
- Common dose-limiting toxicity of many of the plant alkaloid agents
- Many times the damage appears to be dose dependent, and occasionally irreversible
- Nerves that are affected are primarily the peripheral nerves, although cranial nerves and autonomic nerves can also be damaged
Describe cardiac toxicity of antineoplastics
- is a recognized dose-limiting toxicity of several agents
- common with the anthracycline antibiotics (ex. doxorubicin, epirubicin, daunorubicin, idarubicin, mitoxantrone)
- being seen with seam of the monoclonal antibodies
- Risk factors for cardiac damage: age, pre-existing heart disease, concurrent treatment with cyclophosphamide, treatment schedule
What is biological Tx ?
- “uses living organisms, substances derived from living organisms, or synthetic version of such substances to treat cancer”
- approved: monoclonal antibodies, cytokines
- investigational: therapeutic vaccines, gene therapy, adoptive T-cell transfer
What is targeted Tx ?
- “drugs or other substances that block the growth & spread of cancer by interfering with specific molecules involved in tumor growth & progression”
- “drugs that interfere with cell growth signalling or tumor between development, promote the specific death of cancer cells, stimulate the immune system to destroy specific cancer cells & deliver toxic drugs to cancer cells
What was the first molecular target of endocrine Tx ?
estrogen receptors in breast cancer
What are 3 types of endocrine treatment?
- SERMs
- Aromatase inhibitors
- Hormonal agents: Bicalutamide
SERMs
Selective estrogen receptor modulators (SERM’s):
-Tamoxifen
Aromatase Inhibitors
Aromatase inhibitors:
- Exemestane, anastrozole, letrozole
- For post-menopausal women (pre-menopausal women produce enough on their own)
Describe Hormonal agent (Bicalutamide)
Hormonal agents: Bicalutamide:
- Useful for treatment or prostate cancer
- Inhibit the translocation of the androgen receptor not allowing testosterone to bind
- Useful in combination with gonadotropin-releasing hormone analogues
- Oral medication
- Major side effect is diarrhea
Describe monoclonal antibodies for targeted therapy
- Ab engineered to bind to specific targets on cell surface
- IV
- Also used for other illnesses (ex. RA, Crohn’s, psoriasis)
- Risk of anaphylaxis with administration
What are some SE of monoclonal antibodies ?
- Fatigue
- Capillary leak syndrome
- Hepatotoxicity
- Bone marrow suppression
- CNS effects
- Cardiac dysfunction
What are some monoclonal antibodies ?
- trastuzumab
- cetuxiimab
- rituximab
What are some tyrosine kinase inhibitors?
- Imatinib
- Dasatinib
- Nilotinib
Angiogenesis
Tumor cells secrete VGEF to grow so this is a target to kill cancer cells
What does Bevacizumab target?
-Monoclonal antibody that targets VEGF receptor and inhibits angiogenesis
What are some oncologic emergencies?
- FNE/Septic shock
- Hypercalcemia of malignancy
- TLS
- SIADH (intra-vascular fluid excess)
- DIC (simultaneous bleeding and clotting)
Stem Cell Sources:
Allogeneic
Allogeneic: from a donor matched to recipient
- Related: family, usually sibling
- Unrelated: donor from one of the unrelated donor registries
Stem Cell Sources:
Autologous
patient’s own stem cells removed, stores & reinfused
Stem Cell Sources:
Syngeneic
identical twin donor
