Pharm - Therapy of Patients with Cancer
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- Most common cancers
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Solid tumours of the:
- breast
- lung
- prostate
- colon
- rectum
*they have LOW growth fraction (therefore respond POORLY to drugs) - Rarer cancers
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- Lymphocytic Leukemia
- Hodgkin's Disease
- Testicular
*they have HIGH growth fraction (therefore, respond WELL to drugs) - Most common treatment for solid tumours
- Surgery
- Treatment of choice for disseminated cancers (Leukemia, lymphomas, wide-spread)
- Drug Therapy
- 4 Drug Classes
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1. Cytotoxic Agents (most common)
2. Hormones & hormone antagonists
3. Biological response modifiers
4. Targeted drugs - Characteristics of Neoplastic Cells
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- immortality (keep living)
- activated by oncogenes and inactivation of tumour suppression genes
- persistant proliferation - Growth Fraction
- Impact of tissue growth fraction on responsiveness to chemotherapy
- Cell Cycle
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G0 - resting phase
G1- synthesis of RNA & proteins
S - DNA synthesis
G2 - construction of mitotic apparatus
M - Mitosis (cell division) - Chemotherapy drugs are more toxic to tissues that have a HIGH growth fraction such as:
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- bone marrow
- skin
- hair follicles
- sperm
- GI tract - Why do solid tumours respond poorly to chemotherapy?
- there is a greater % of cells in resting phase than proliferation phase
- Strategies for maximum benefits of chemotherapy
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- intermittent chemotherapy (allows time for normal cells to repair themselves)
- combination chemotherapy
- optimizing dosing schedules
- regional drug delivery (intra-arterial or intrathecal) - Major toxicities of Cancer Chemotherapy
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1. Myelosuppression (Bone marrow suppression) - neutropenia, thrombocytopenia, anemia)
2. GI tract (Stomatitis) - N/V, diarrhea
3. Alopecia
4. Hyperuricemia (high levels of URIC acid - can lead to kidney problems)
5. Reproductive TOXICITY
6. EXTRAVASTATION
7. Carcinogenesis - One of these 3 should be possible before providing cancer treatment
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1. Cure
2. Prolongation of life
3. Palliation - Factors influencing Chemotherapy Selection:
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1. Patient Factors (Age, performance status, previous cancer treatment, prognosis)
2. Disease Factors (size & location, lymph node involvement & spread)
3. Chemotherapy Factors - potential side effects and patients ability to tolerate them - Calculation of Chemotherapy Dosages
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- based on BSA
- based on height (cm) and weight (kg)
- dosed as mg/m^2
- re-evaluated with each chemotherapy cycle
- sensitive to weight changes - 4 classifications of chemotherapy drugs
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1. Alkylating Agents
2. Antimetabolites
3. Anti-tumor Antibiotics
4. Vinca (Plant) Alkaloids - Alkylating drugs
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- cell cycle: NON-SPECIFIC
- "Alkyl" group causes breaks in DNA sequence
- common in COMBINATION therapy - Antimetabolites
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- cell cycle: S phase
- act as FALSE metabolites (which are incorporated into the DNA strand & prevent DNA & RNA synthesis) - Antitumor Antibiotics
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- cell cycle: NON-SPECIFIC
MOA:
1. break DNA strands
2. inhibit DNA & RNA synthesis
3. alter CM (cell membrane)
- NATURAL compounds (found in strains of STREPTOMYCES)
- streptomyces (soil fungal organism) - 3 Common forms of Plant Alkaloids
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1. VINCA ALKALOIDS (M PHASE) - crystallize microtubules of mitotic spindles
2. TAXANES (M PHASE) - cells are prematurely thrown into cell division or cell division arrested (stopped)
3. TOPOISOMERASE INHIBITORS (S PHASE) - inhibits topoisomerase and causes cell death - Targeted cancer therapies
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Growth factor receptor inhibitors
1. Tyrosine Kinase Inhibitors (Tarceva & Sutent)
2. Her 2 protein Inhibitor (ex. Herceptin) - Hormone Therapies
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- used to manage hormone sensitive cancers such as breast and prostate
- suppress or eliminate hormonal growth factors
(ex. Tamoxifen) - Common adverse effects of chemotherapy
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1. Myelosuppression (increase risk for infections) - leukopenia, neutropenia, anemia, thrombocytopenia
2. Integument effects - alopecia & extravastation
3. GI effects - stomatitis
4. Renal or Bladder effects - HEMATURIA (blood in urine) increased uric acid or creatinine)
5. Reproductive effects - women: change in menses; men - decreased sperm - How to manage neutropenia (low neutrophils)
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1. prevent infection (hygiene)
2. meds: antibiotics/virals/fungals
3. granulocyte stimulating factors (Neupogen or Neulasta)
4. hold/delay therapy - How to manage anemia
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- monitor breathing & HR
- encourage rest
- blood transfusion (if severe)
- meds: erythropoietin growth factors (Eprx, Aranesp)
- high iron, folate, B12
*takes approx. 25 days for RBCs to form - How to manage Thrombocytopenia
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1. monitor for bleeding
2. prevent injury and bleeding: avoid bruises or cuts
3. platelet transfusions - Effects of extravasation
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- pain
- ulceration
- necrosis
- sloughing of damaged tissue - How to manage extravasation
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1. Stop chemotherapy
2. Infuse SALINE or DEXTROSE
3. Aspirate chemo drug as possible
4. hot/cold compresses
5. MEDS: CORTICOSTEROIDS, SODIUM THIOSULPHATE - How to manage Stomatitis
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- avoid mouthwashes & specialty toothpastes
- use soft bristle toothbrush
- popsicles/ice chips
- salt water rinses
- meds: "magic mouthwash" - 3 types of N/V
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1. Acute (within 24 hours)
2. Delayed (after 24 hours)
3. Anticipatory (prior to treatment) - How to manage N/V
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- cater to food preferences
- encourage fluids
- meds: anti-emetics - Anti-emetics
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1. Serotonin Antagonists
- Ondansetron
- Granisetron
- usually COMBINED WITH: corticosteroids (increase effects)
2. Metoclopramide or Phenotiazine derivatives) - blocks Dopamine receptors in CTZ
3. Dimenhydrinate (Gravol) - blocks Histamine receptors - How to manage diarrhea
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- increase FIBER
- avoid DAIRY
- increase fluid
- Meds: IMMODIUM, LOTOMIL, ATROPINE - How to manage Renal & Bladder Toxicities
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- increase fluid
- observe urine for blood
- monitor lab values for high levels of URIC acid & CREATININE
- Meds: DIURETICS, renal protectants (Mesna)