Oncology Flashcards
Causes of Cancer
Genetic Mutations
1) Proto-Oncogenes: Causes the inability to stop replication
2) DNA Repair Genes
3) Tumor Suppressor Genes
External Factors: Chemicals, Radiation, Sunlight exposure, tobacco and alcohol use, bacteria and viruses
Internal Factors: Hormones, Older Age, Inherited gene mutations (BRCA genes for breast cancer)
How can we lower our Cancer Risk?
1) Maintaining a healthy lifestyle (exercise, healthy eating, avoid tobacco)
2) Regular check ups and vaccinations (e.g. HPV)
3) Skin protection
4) Routine cancer screening
Cancer Screening
Breast Cancer (Age >= 45)
-Annual Mammogram
Cervical Cancer (Age 25-65)
-Pap Smear every 3 years
-HPV every 5 years
Colorectal Cancer (Age >= 45)
-Stool based test (annually or every 3 years)
-Visual exams (Colonoscopy every 10 years)
Lung Cancer (Age >= 50)
-Annual CT if >= 20 pack-year smoking history, or still smoking, or quit smoking within the past 15 years
Warning Sign of Cancer
C - Change in bowel or bladder habits
A - A sore that does not heal
U - Unusual bleeding or discharge
T - Thickening or lump in the breast or elsewhere
I - Indigestion or difficulty swallowing
O - Obvious change in a wart or mole
N - Nagging cough or hoarseness
Cancer Staging
T (Tumor size)
N (Node Status)
M (Metastasis)
*Higher the number, the more advanced the cancer is!
Treatment Types
1) Surgery <—Localized
2) Radiation (High-energy X-rays to destroy cancer cells) <— Localized
3) Chemotherapy <—Affects the entire body
4) Hormone Therapy (Stops or slows the growth of certain cancers that use hormones to grow)
5) Targeted Therapy (Attacks specific cancer cells, TKi, -mabs)
6) Immunotherapy (Uses the body’s immune system to fight cancers)
Neoadjuvant (Radiation, Chemo) - Given before Primary, to shrink tumor
Primary Treatment (Surgery) - Eliminate cancer cells
Adjuvant Therapy (Radiation, Chemo) - Given after Primary, to eradicate residual disease
Alkylating Agents Drug Class
MOA: These work by cross-linking DNA strands and inhibiting protein synthesis and DNA synthesis
Common Alkylating Agents:
1) Cyclophosphamide
2) Ifosfamide
3) Busulfan
4) Carmustine
Side Effects:
-Alopecia
-Mucositis
-Secondary malignancies
Cyclophosphamide & Ifosfamide
Safety Concern:
1) Hemorrhagic cystitis, caused by acrolein, a toxic metabolite of Cyclo and Ifosfamide.
2) Myelosuppression
Give MESNA, a chemoprotectant, which is given prophylactically for hemorrhagic cystitis.
Busulfan & Carmustine
Safety Concerns:
1) Pulmonary Toxicity
2) Neurotoxicity (Prevention: give antiseizure meds prior to Carmustine)
Platinum Based Compounds
MOA: Same as Alkylating Agents. They cross-link DNA and interferes with DNA synthesis and cell replication.
DRUGS:
1) Cisplatin
2) Carboplatin
3) Oxaliplatin
Side effects due to Platinum content:
-Peripheral Neuropathy (Pins and Needles)
-Ototoxicity
-Nephrotoxicity
Cisplatin
Safety Concerns:
1) Nephrotoxicity (Boxed Warning)
-Cisplatin is the MOST Nephrotoxic of all Chemo drugs, and is associated with the highest incidence of CINV (Chemo-induced N/V)
-Limit dose to <= 100 mg/m2. Doses higher needs to be confirmed with provider.
-Amifostine (Ethyol) is given before cisplatin to reduce renal toxicity
2) Ototoxicity
-Prior hearing impairment is contraindicated
-Perform audiograms at baseline and before each dose.
Carboplatin
Doses are calculated via Calvert Formula:
Total Carboplatin Dose (mg) = (Target AUC) x (GFR+25)
Anthrocyclines
MOA:
1) Intercalation into DNA
2) Inhibition of Topoisomerase II
3) Creation of O2 free-radicals that damage cells
DRUGS:
1) Doxorubicin & all ‘-rubicin’ (Red discoloration)
2) Mitoxantrone (Blue discoloration)
Doxorubicin
-All ‘rubicins’ are potent vesicants
-Drug is red and causes RED urine, tears, sweat and saliva!
-Lifetime Cumulative Dose: 450-550 mg/m2
-Dexrazoxane is given with Doxorubicin as a chemoprotectant against Cardiotoxicity, when cumulative dose > 300!
-LVEF before and after treatment
-Monitor HF signs and symptoms during treatment
*REMEMBER TO CALCULATE CUMULATIVE DOSE!!!
Topoisomerase I & II Inhibitors
Topoisomerase is responsible for the coiling and uncoiling of DNA.
MOA: Block the coiling and uncoiling of DNA. This causes breaks in the DNA.
Topoisomerase I: S-phase
Topoisomerase II: G2-phase
DRUGS:
1) Irinotecan (Topoisomerase I) - diarrhea
2) Etoposide (Topoisomerase II) - infusion hypotension (infuse over 30-60 mins)
3) Bleomycin (Topoisomerase II) - CUM LIFETIME DOSE MAX: 400 U, Not Myelosuppressive!
IRINOTECAN:
-Diarrhea (Boxed Warning!) ‘I run to the can’. Onset: During or immediately after infusion
-Cholinergic Symptoms (Salivation, abdominal cramping, sweating)
Vinca Alkaloids
MOA: Inhibit the function of microtubules during the M phase of the cell cycle.
DRUGS:
1) Vincristine (More CNS toxicity) <—Major 3A4 substrate! Dont give with azoles
2) Vinblastine (More Bone marrow suppression)
-Peripheral Neuropathy (prevent with dose cap of vincristine)
-Antonomic Neuropathy (constipation)
*Accidental Intrathecal administration can cause progressive paralysis and death!
*Vincristine: Dose cap of 2mg/dose, regardless of calculated dose
Taxanes
MOA: Inhibits function of microtubules in M-phase of cell cycle
DRUGS:
1) Paclitaxel
2) Docetaxel (additional fluid retention side effect)
-Peripheral Sensory Neuropathy
*Boxed Warning of hypersensitivity reactions!
-Premedication with a systemic steriod, diphenhydramine and H2RA
-Give Taxanes BEFORE Platins
-Leeching occurs. Needs non-PVC bag and tubes with a 0.22 micron filter
Pyrimidine Analog Anti-metabolites
MOA: Inhibit pyrimidine synthesis during the S-phase of the cell cycle. F-UMP is incorporated into RNA to replace uracil, while 5-dUMP inhibits thymidylate synthetase
DRUGS:
1) Fluorouracil (5FU)
2) Capecitabine (Xeloda) (Oral prodrug which is converted to 5FU)
-Leucovorin is given with 5FU to increase efficacy. It helps 5FU to bind more tightly to its target
-Causes sig increase in INR up to 1 month after treatment.
Side Effects:
-Hand-foot syndrome (Capillary drug leakage)
-GI Toxicity (Diarrhea & Mucositis)
Folate Antimetabolites (Methotrexate)
Brand: Trexall
MOA: Involved in the folic acid cycle by blocking purine and pyrimidine biosynthesis during the S-phase.
-Folic acid/Folic Acid analogs + B12 may be required to reduce toxicity
-Leucovorin must be given with high doses. It is the active form of folic acid! Regular Folic Acid is not effective
-Also used for RA and Psoriasis. Cancer doses are much higher.
-Antidote: GLUCARPIDASE
Toxicities:
-Nephrotoxicity (with high doses >= 500 mg/m2). IV Bicarb is given to reduce this effect
-GI Toxicity (Mucositis, Diarrhea)
Mucositis
-Results from direct DNA damage which upregualtes cytokines in the mucosa.
-It presents as painful mouth ulcers, difficulty eating or drinking
-It is self-resolving
Prevention:
-Maintain good oral hygiene (soft toothbrush BID)
-Hold ice chips in mouth prior to chemo, and several hours after infusion. This leads to decrease perfusion in the mouth resulting in decreased drug delivery in the mouth.
Monoclonal Antibodies
-Targeted Therapy: recognizes specific biomarkers and proteins that control cancer growth
-Pharmacogenomics testing is required to see if the patient carries specific genes, since these therapies target specific antigens or receptors.
-IV only. Therefore, infusion related reactions. Can be prevented with premedication (steriod, APAP, diphenhydramine)
MOA: (Single or combo)
-Enhance the immune system’s ability to destroy cancer cells
-Interrupt signals that causes cancer growth
-Inhibit angiogenesis (stop blood vessels from forming in tumors)
-Induce apoptosis
COMMON DRUGS:
1) Rituximab
2) Cetuximab
3) Trastuzumab
4) Bevacizumab
Contains ‘ci’ : targets circulatory system
Contains ‘tu’: targets tumor growth
Rituximab
Brand: Rituxan
MOA: Binds to CD20 antigen
-Premedicate with dihphenhydramine, steriod and acetaminophen
-Boxed Warning: HepB reactivation, SJS/TEN, PML
-Check hepB before administration
Cetuximab
MOA: Binds to epidermal growth factor receptor (EGFR)
-Check for EGFR expression first
-Dermatologic Toxicity
Trastuzumab
Brand: Herceptin
MOA: Binds to human epidermal growth factor receptor 2 (HER2)
-Pgx: Check for HER2 expression first. Must have HER2 overexpression!
-Cardiotoxicity (Monitor LVEF before and after treatment)
Bevacizumab
Brand: Avastin
MOA: Binds to vascular endothelial growth factor (VEGF)
-Impairs wound healing. Do not use 28 days before or after surgery
-GI perforation
-
Bevacizumab
Brand: Avastin
MOA: Binds to vascular endothelial growth factor (VEGF)
-Impairs wound healing. Do not use 28 days before or after surgery
-GI perforation
-
Immunotherapy Drugs
DRUGS:
1) Pembrolizumab (Keytruda)
2) Nivolumab
3) Ipilimumab
MOA: Bind to programmed death receptor-1 (PD-1) resulting in increased T-cell activation. It activates the immune system to recognize and kill cancer cells. (Pembrolizumab and Nivolumab)
MOA (Ipilimumab): Binds to cytotoxic t-lymphocytes antigen-4 (CTLA-4)
Tyrosine Kinase Inhibitors (-nibs)
DRUGS:
1) Imitinib (Gleevec)
2) Dasatinib
3) Nilotinib
4) Alot others
MOA: targets BCR-ABL fusion gene
-QT Prolongation
-GI Upset
Summary of MAX Dose for highly toxic drugs
1) Bleomycin: LCD of 400 Units (Pulmonary Toxicity)
2) Doxorubicin: LCD of 450-550 mg/m2 (Cardiotoxicity)
3) Cisplatin: Do not exceed 100 mg/m2 per CYCLE (Nephrotoxicity)
4) Vincristine: 2 mg cap per dose (Neuropathy)
ChemoMAN
N: Neurotoxicity (Carmustine) - head
C: Nephro- and Ototoxicity (Carboplatin and Cisplatin) - mouth, kidney, ears
M: Mucositis (Methotrexate, 5FU, Capecitabine) - mouth
P: Pulmonary toxicity (bleomycin, busulfan, carmustine) - lungs
D: Doxorubicin and other anthracyclines (Cardiotoxic) - heart
IP: Ifosfamide and Cyclophosphamide (hemorrhagic cystitis) - bladder
VT: Vinca and Taxoids (Peripheral neuropathy) hands and feet
BMS: Bone Marrow Suppression (alot of meds)
Summary of Chemotherapy Adjuvant Therapy
1) Cisplatin: Amifostine and hydration
2) Doxorubicin: Dexrazoxane
3) Fluorouracil: leucovorin, antidote (Uridine triacetate)
4) Ifosfomide: MESNA and hydration
5) Iranotecan: Atropine and Loperamide
6) Methotrexate: leucovorin, antidote (Glucarpidase)
Myelosuppression
This is a decrease in bone marrow activity, resulting in:
1) Decreased WBC (Neutropenia) - increased infection
2) Decreased RBC (Anemia) - weakness/fatigue
3) Decreased Platelets (Thrombocytopenia) - bleeding (Treat with platelet transfusion if really low)
-The lowest point that WBC and Platelet reach is called nadir. This is typically 7-14 days after chemo.
-WBC and Platelets generally recover 3-4 weeks post-treatment.
-The next dose of chemo is given after the WBC and Platelets have returned to safe levels.
Neutropenia
-Assessed by calculating ANC
-ANC < 1000: Neutropenia
-ANC < 500: Severe Neutropenia
-ANC < 100: Profound Neutropenia
Growth Colony Stimulating Factors (G-CSFs)
-Filgrastim and Pegfilgrastim stimulate the production of WBC in the bone marrow
-Given prophylactally after chemo in high-risk patients
-Cause bone pain, rash
Febrile Neutropenia (development of a fever)
-Treat with empiric antibiotics
-High risk patients (IV antipseudomonal antibiotics)
-Low risk (Oral antipseudomonal antibiotics)
Anemia
-Rarely an ESA is used (Erythropoiesis-stimulating agent)
-Epotein alfa
-Darbepoetin alfa
-ESAs can shorten survival and increase tumor progression
-Recommended for palliation only, not for curative intent.
Chemotherapy-induced Nausea and Vomiting
Classification:
1) Anticipatory
2) Acute (within 24 hours after chemo)
3) Delayed (> 24 hours after chemo)
4) Breakthrough NV (anytime after despite prophylaxis)
Types of Antiemetics
1) Neurokinin-1 receptor antagonists
-Aprepitant
-Fosaprepitant
-Rolapitant
2) Serotonin Receptor antagonists (5HT3 RA)
-Ondansetron
-Granisetron
-Palosetron
-Dolasetron
3)Dopamine Receptor antagonists
-Olanzapine
-Prochlorperazine
-Promethazine
-Metoclopramide
-Haloperidol
Others:
-Dexamethasone
-Dronabinol
-Lorazepam
High Emetic Risk Drugs
-Cisplatin
-Anthracycline + Cyclophosphamide
Add 3 or 4 Antiemetic Drugs
1) NK1 RA + 5HT3 RA + Olanzapine + Dexamethasone
2) NK1 RA + 5HT3 RA + Dexamethasone
3) Palonosetron + Olanzapine + Dexamethasone
Moderate Emetic Risk Drugs
Add 2 or 3 Antiemetic Drugs
1) NK1 RA + 5HT3 RA + Dexamethasone
2) 5HT3 RA + Dexamethasone
3) Palonosetron + Olanzapine + Dexamethasone
Low Emetic Risk Drugs
1 Antiemetic Drug Regimen:
1) 5HT3 RA
2) Dexamethasone
3) Metoclopramide
4) Prochlorperazine
Neurokinin-1 Receptor Antagonists (NK1 RA)
MOA: Inhibits Substance P
DRUGS:
1) Aprepitant
2) Fosaprepitant
3) Rolapitant
Serotonin Receptor Antagonists (5HT3 RA)
MOA: Blocks Serotonin peripherally and centrally
DRUGS:
1) Ondansetron
2) Granisetron
3) Palonosetron (Longest T1/2)
4) Dolasetron
Safety Concern:
-QT Prolongation - especially IV admin
-Serotonin Syndrome
Dopamine Receptor Antagonists
MOA: Blocks Dopamine in CNS
DRUGS:
1) Olanzapine (Zyprexa)
2) Prochlorperazine
3) Promethazine
4) Metoclopramide (Reglan)
5) Haloperidol
Safety Concern:
-Extrapyramidal side effects (Avoid in patients with Parkinsons)
-QT Prolongation
Other Antiemetics
1) Dexamethasone
2) Scopolamine (Transderm Scop)
3) Dronabinol (Marinol)
4) Nabilone (Cesamet)
5) Lorazepam (Ativan)
Treatment of Chemo-Induced Diarrhea
1) Loperamide (MAX 16 mg/day)
2) Diphenoxylate/Atropine
Treatment of Chemo-Induced Oral Mucositis
1) Magic mouthwash
2) Prevention by brushing with soft toothbrush and ice chips
What is BRCA1 and BRCA2?
Tumor suppressor genes
-Mutation of these genes cause cells to grow uncontrollably
Breast Cancer Risk
1) Female
2) Family History
3) Genetics
-BRCA1 And BRCA2 Mutations
-Klinefelter Syndrome (Extra X Chromosome in Males)
Treatment of Breast Cancer
1) Surgery
2) Radiation
3) Chemotherapy
-Hormone Receptor-Positive Treatment (Endocrine Therapy)
-HER2-Positive Treatment
-Estrogen-containing medications are contraindicated in patients with any history of breast cancer
Hormone Receptor-Positive Treatment (Endocrine Therapy)
Some breast cancer cells have receptors that attach to Estrogen and/or Progesterone.
-When attachment occurs, it can stimulate the growth of the cancer
-Treatment stops the attachment of these hormones, or can lower hormone levels in the body
-Tamoxifen, a SERM, binds to estrogen receptors and blocks the effects of estrogen in both pre and post menopausal women.
-Anastrazole
Tamoxifen Safety Concerns
Tamoxifen is a pro-drug which is converted to ENDOXIFEN via 2D6
1) Vasomotor symptoms (hot flashes, night sweats) - Venlafaxine is used for Hot flashes
2) Increased risk of Thromboembolic events (Boxed Warning)
3) Increased risk of Uterine or Endometrial Cancer (Boxed Warning)
4) Vaginal discharge/bleeding
5) Decreased bone density - Supplement with Ca+VitD
Fulvestrant
MOA: SERD (Selective Estrogen Receptor Degrader)
-Used for Advanced Breast Cancer
-Increases LFTs
Aromatase Inhibitors
MOA: Aromatase Inhibitor, blocks the aromatase enzyme from converting androgens to estrogens in peripheral tissues. This is only for Post menopausal women.
-Anastrazole (Arimidex)
-Letrozole
Safety Concerns:
-Osteoporosis
-Increased risk of CV events
-Hot flashes/Night Sweats
HER-2 Positive Treatment
HER2 is a protein that regulates the growth of breast cells. If a breast cell over expresses HER2 receptors, the cell can grow uncontrollably.
-Trastuzumab (Herceptin)
Prostate Cancer Treatment
-Testosterone can make the cancer grow
1) Gonadotropin-Releasing Hormone Agonists
-Leuprolide
-Goserelin
2) Gonadotropin-Releasing Hormone Antagonists
-Degarelix
-Relugolix
3) Antiandrogens
-Bicalutamide
-Flutamide
-Nilutamide
Tumor Lysis Syndrome
Oncologic Emergency
-This results from the rapid breakdown of tumor cells and the release of cellular components (K, PO4, Nucleic Acid) into the blood. This overwhelms the body to excrete these, and leads to its accumulation.
-This leads to Hyperkalemia, Hyperphosphatemia, Hypocalcemia, Hyperuricemia
Management:
1) Aggressive IV Hydration
2) Electrolyte correction
3) Urate lowering therapies
Hypercalcemia of Malignancy
Causes:
1) Tumor secretion of Parathyroid hormone-related protein (Parathyroid stimulates reabsorption of Ca in the kidneys)
2) Bone Metastases (Breakdown of bone causes Ca to be released into the blood)
3) Calcitriol Overproduction
TREATMENT:
1) IV hydration with NS
2) IV bisphosphonate (Zoledronic acid or Pamidronate)
3) Calcitonin
4) Denosumab
