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74 Cards in this Set
- Front
- Back
Cancer (Definition) |
A group of diseases: 1.) uncontrolled cellular growth 2.) local tissue invasion 3.) distant metastases |
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Most commonly diagnosed cancer in men? |
Prostate |
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Most commonly diagnosed cancer in women? |
Breast |
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Most common cause of cancer death in women? |
Lung |
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Most common cause of cancer death in men? |
Lung |
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Age group for which cancer is the leading cause of death? |
> 85 years of age |
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Lifetime probability of developing cancer for men and women? |
men = 1 in 2 women = 1 in 3 |
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Top 3 causes of cancer death in children and adolescents? |
0-14 years: 1.) Brain, 2.) Leukemia, 3.) Soft Tissue 15-19 years: 1.) Leukemia, 2.) Bone/Joints, 3.) Brain |
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The 2 major influences in the development of cancer in Americans? |
1.) Cigarette smoking 2.) Age |
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Obesity is a risk factor for which 3 cancers? |
1.) Colon 2.) Prostate 3.) Ovarian |
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What lack in diet is associated with higher rates of cancers? |
5 or more servings of vegetables daily |
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4 Processes in Carcinogenesis |
1.) Initiation 2.) Promotion 3.) Conversion 4.) Progression |
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Initiation (Definition) |
irreversible damage to normal cells caused by exposure to carcinogenic substances |
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Promotion (Definition) |
carcinogens alter the environment to favor growth of the mutated cells possibly reversible |
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Conversion (Definition) |
the transformation of a normal cell to a cancerous cell may take 5-20 years |
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Progression (Definition) |
further genetic changes leading to increased cell proliferation |
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Angiogensis (Definition) |
the development of new blood vessels by the tumor in order to grow |
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Who do we screen for cancer? |
Asymptomatic people with risk factors for certain kinds of cancer because... - of the low cure rate of metastatic cancer if discovered too late - the expense of screening |
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Describe the screening schedule for breast cancer. |
Clinical Breast Exam: - starting at age 20 - at least every 3 years, then annually prior to mammograms Mammogram: - starting at age 40 - annually |
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Describe the screening schedule for cervical cancer. |
Pap Smear: - starting at age 21 to 29 - every 3 years HPV and Pap Tests: - starting at age 30 to 65 |
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Describe 5 screening schedules that both men and women should follow starting at age 50. |
1.) Fecal Occult Blood Test - annually 2.) Flexible Sigmoidoscopy - every 5 years 3.) Double Contrast Barium Enema - every 5 yrs 4.) Colonoscopy - every 10 years 5.) CT Colonography - every 5 years |
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Goals of Cancer Treatment |
1.) Cure 2.) Prolong Life 3.) Palliation |
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Adjuvant Therapy (Definition) |
systemic therapy that is administered to treat any existing micrometastases remaining after surgical excision of localized disease. |
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Neoadjuvant Therapy (Definition) |
treatment given prior to the definitive local treatment, usually prior to surgery. |
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What order of kinetics do cancer treatments follow? |
1st order (cancer drugs kills a constant proportion of tumor cells) |
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What kind of cells do most cancer treatments target? |
Rapidly proliferating cells, whether cancerous or no. (Ex: mucus membranes, hair follicles, bone marrow) |
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How are cancer treatments dosed? |
The Maximum Tolerated Dose (MTD) is the most effective, but requires several cycles with resting periods in between. The MTD is given up to the Dose Limiting Toxicity (DLT) for any one anticancer drug at which point it's too dangerous to continue. |
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Gompertzian Growth Curve-Log-Kill Hypothesis |
Cancer cells are clinically undetectable til 10^5 - immunotherapy = greatest benefit 10^5 - 10^12 cells = symptomatic, diagnosis possible, bulk reduction of tumor is necessary 10^12 cells = plateau growth phase, 1 kg tumor, incapacitating symptoms, death |
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Why Combination Chemotherapy? |
1.) Maximal cell kill within tolerated toxicity 2.) Broader range of coverage 3.) Prevent development of resistant lines |
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Metronomic Therapy (Definition) |
For molecularly-targeted drugs only. Taken continuously until disease progression or unacceptable adverse events occur. |
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4 Classes of DNA-Damaging Drugs |
1.) Alkylating Agents 2.) Antibiotics 3.) Topoisomerase Inhibitors 4.) Anti-Metabolites |
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Characterization of DNA-Damaging Drugs |
Interfere with transcription and reduplication - Affected cells undergo cell cycle arrest and apoptosis * Mutagenic, Teratogenic, and Carcinogenic Affect rapidly proliferating cells |
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Alkylating Agents (Mechanism of Action) |
Overall: Attach alkyl groups to DNA * groups on DNA bases prevent DNA synthesis, RNA transcription = fragmentation * crosslink DNA strands = no DNA separation for reduplication or transcription * groups induce mispairing leading to mutations |
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8 Alkylating Agents |
1.) Nitrogen Mustards * 2.) Nitrosureas * 3.) Triazenes and Hydrazines 4.) Ethylene Imines and Methylmelamines 5.) Benzoquinone-containing 6.) Alkyl Sulfonates 7.) Illudins 8.) Platinum drugs * |
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Nitrogen Mustards |
1st Gen: Mechlorethamine *, N-0xide 2nd Gen *: Chlorambucil, Melphalan, Bendamustine, Spiromustine 3rd Gen: Uramustine Steroid-Coupled: Estramustine phosphate, DHEA mustard, Prednimustine Phosphoramide *: Cyclophosphamide, Ifosfamide |
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Which nucleotide is most susceptible to alkylation? |
Guanine |
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Phosphoramide Mustards (Mechanism of Action) |
Prodrugs metabolized by CYP450 to phosphoramides and acrolein Phosphoramides alkylate DNA Acrolein alkylates proteins (AE: Bladder Toxicity) |
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Cyclophosphamide (Cytoxan) |
Uses: solid and hematologic tumors, bone marrow transplant (BMT) AE: hemorrhagic cystitis (bladder toxicity) (not as much as Ifosfamide, may give Mensa) DLT: leukopenia = 8-14 days |
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Ifosfamide (Ifex) |
Uses: sarcomas, testicular cancer, lung cancer AE: *hemorrhagic cystitis (Mensa mandatory) |
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Nitrosoureas (Mechanism of Action) |
Carmustine (BiCNU), Lomustine (CeeNU), Streptozocin (Zanosar) Lipid Soluble, often oral dosing, long nadir |
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Carmustine (BiCNU) |
Uses: brain tumors, Hodgkin's Dx, mycosis fungoides, cutaneous T-cell lymphoma *Dosage Forms: Injection (in EtOH), topical, Gliadel wafer (brain implantation) *Long time to nadir (21-28 days) *Administer every 6 weeks |
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Lomustine (CCNU, CeeNU) |
Uses: primary brain tumors Dosage Forms: oral capsule (10 mg increments) Long time to nadir (dose every 6 weeks) |
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Platinum Compounds (Mechanism of Action) |
Crosslink DNA like mustards - intrastrand (bind twice, same strand) - interstrand (bind twice, crosslink) - monoadduct (bind once) - intermolecular (bind to DNA and protein) |
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Cisplatin (Adverse Effects) |
Nephrotoxicity Nausea/Vomiting (acute and delayed) Neuropathy Myelosuppression (slight) Ototoxicity |
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Carboplatin (Adverse Effects) |
Uses: broad spectrum AE: nephrotoxicity, ototoxicity, neuropathy, N/V (less than cisplatin) myelosuppression DLT: Thrombocytopenia |
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Carboplatin (Dosing) |
Calvert Formula Target AUC (6mg/mL/min) * [GFR + 25] (25 = constant representing non-renal Cl) |
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Oxaliplatin |
Uses: colorectal cancer, GI tumors Often used in combo with 5-FU or Capecitabine Dose: 135 mg/m^2 |
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Oxaliplatin (Adverse Effects) |
Hypersensitivity rxn *DLT: Neurotoxicity (acute and delayed) Nephrotoxicity Fatigue Myelosuppression N/V/D Pulmonary Fibrosis *rare |
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Oxaliplatin (DLT elaborated) |
Acute Neurotoxicity: peripheral neuropathy, visual changes, auditory toxicity, *pharyngolaryngeal dysesthesia
Delayed Neurotoxicity: cumulative peripheral sensory neuropathy
Proph: Avoid cold temperatures and food/drink! (pharyngolaryngeal dysthesias) |
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Oxaliplatin (N/V tx) |
5-HT3 antagonist (setron drug) + dexamethasone (ex: Ondasetron, Granisetron, Palonosetron, Dolasetron, Metaclopramide) |
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Busulfan (Myleran) |
Alkyl Sulfonate Affect early WBC precursors Uses: chronic myeloid leukemia (CML), BMT Dosage Forms: oral
*Prolonged nadir time AD: "Busulfan lung" = pulmonary fibrosis, seizures (proph. with phenytoin) |
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2nd Gen Nitrogen Mustards |
Chlorambucil, Melphalan, Bendamustine More stable with inclusion of 6-member ring and long hydrocarbon/carboxyl tail |
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Chlorambucil (Leukeran) |
Uses: chronic lymphocytic leukemia (CLL), non-Hodgkin's Lymphoma (NHL) Dosage Form: 2 mg oral tabs Dose every 2-4 weeks AE: bone marrow suppression, N/V, pyrexia |
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Melphalan (Alkeran) |
Uses: multiple myeloma, BMT Dosage Forms: oral and IV 9 mg/m^2 PO x4-7 days Q4-6 weeks (BMT = 100 mg/kg) |
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Bendamustine (Treanda) |
Uses: Chronic lymphocytic leukemia (CLL), non-Hodgkin's Lymphoma (NHL) AE: bone marrow suppression, N/V, pyrexia (more than chlorambucil) |
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Topoisomerase Inhibitors (Mechanism of Action) |
Prevents Topoisomerase 1 or 2 from uncoiling the supercoiled DNA for transcription and reduplication Topoisomerase 1 inhibitors: Camptothecins, Indolocarbazoles, Indenoiseoquinolines Topoisomerase 2 inhibitors: Podophyllotoxins, Quinoxalines, Antibiotics |
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Irinotecan (Camptosar) |
Camptothecin (T1) Uses: Colorectal cancer
AE: Diarrhea (acute and delayed), neutropenia (dose dependent), N/V, dehydration, alopecia, mucositis, acute pulmonary toxicity? |
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Irinotecan (Diarrhea tx) |
Acute: - atropine 0.25 - 1 mg IVP Delayed: - loperamide 4 mg PO LD, then 2 mg PO Q2h ATC until resolved for 12 hours |
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Etoposide (VP-16, Vepesid) |
Epipodophylotoxin (T2) Uses: Lung cancer, NHL, BMT
Dosage Form: in EtOH, IVPB (hypotension), 50 mg PO capsules (F= 50%) |
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5 Classes of Antitumor Antibiotics |
1.) Cyclopropylpyrroloindole 2.) Minor-Groove DNA-binding 3.) Aminoquinone 4.) Polycyclic Aromatic (anthracyclines) 5.) Enediyne |
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2 Broad Classes of Antitumor Antibiotics |
1.) Alkylate DNA (Cyclopropylpyrroloindoles, minor groove binding, aminoquinones) 2.) Redox Cycling (Polycyclic aromatics, enediynes) |
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Redox Cycling Antibiotics (Class Adverse Effects) |
Cardiotoxicity |
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Bleomycin (Blenoxane) |
4 different proteins from bacteria Uses: testicular, NHL, head/neck cancers AE: pulmonary toxicity, pyrrexia, mucositis |
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Polycyclic Aromatics (aka Anthracyclines) |
Doxorubicin, Amrubicin, Epirubicin, Valrubicin, Pirarubicin, Berubicin MOA: intercalates between DNA base pairs and generates free oxygen radicals using the carbonyls on its B ring |
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Doxorubicin (Adriamycin) |
Uses: solid and hematologic tumors AE: cardiotoxicity (max = 550 mg/m^2 for life), myelosuppression, N/V/D, red urine, vesicant, alopecia, radiation recall, mucositis Dose: 25-60 mg/m^2 IVP |
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Dexrazoxane (Zinecard) |
MOA: Metal Chelator Uses: Cardioprotection in women with metastatic breast cancer who have received 300 mg/m^2 doxorubicin AE: myelosuppression, N/V, alopecia, LFT elevation |
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Mitozantrone (Novantrone) |
Uses: breast cancer, NHL, acute leukemia, ovarian cancer, metastatic prostate cancer (+ prednisone) AE: cardiomyopathy, N/V, alopecia (less than other anthracyclines), blue/green secretions Dose: 10-12 mg/m^2 IVP or IVPB |
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Anti-Metabolites (Classes and Subclasses) |
1.) Anti-Folates - Dihydrofolate Reductase inhibitors - Thymidylate Synthase inhibitors - Glycinaminde Ribonucleotide Formyl Transferase inhibitors - Dihydropteroate Synthase inhibitors 2.) Anti-Pyrimidines - Uracil analogs - Cytidine analogs 3.) Anti-Purines - 1st and 2nd generation |
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Anti-Metabolites (Mechanism of Action) |
1.) Serve as false building blocks 2.) Inhibit synthesizing enzymes - prevent synthesis of DNA and RNA Non-selective, therefore best localized |
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Methotrexate (Trexall, Rasuvo) |
MOA: Anti-Folate (Dihydrofolate Reductase-i) Uses: solid and hematologic tumors (ex: breast, lung, head/neck cancers, sarcomas) Dosage Forms: injection including intrathecal Dose: 12 mg/m^2 |
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Methotrexate (Adverse Effects + Risk Factors) |
AE (dose dependent) myelosuppression, N/V, mucositis, hepatotoxicity, neuro/nephrotoxicityRisk Factors: renal dysfunction, prior use of nephrotoxins, pleural effusion, ascites, GI obstruction, poor hydration, acidic urine Dose > 100/m^2 requires leucovorin rescue |
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Methotrexate (Monitoring) |
Low Risk: T1/2: < 3.5 H C24H: < 5 x 10^-6 M Leucovorin = 10 mg/m^2 Q6H for 72H (standard low dose)
High Risk: Monitor until < 1 x 10^-8 M and escalate leucovorin as needed |
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Fluorouracil (5-FU) |
Uses: GI tumors, colorectal cancer, pancreatic 2nd line in breast, lung and head/neck Dose: 500-1000 mg/m^2 IVP or 24H CIVI |
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Fluorouracil (Adverse Effects) |
CIVI: mucositis, diarrhea, hand-foot syndrome IVP: neutropenia Elevated LFTs, coronary artery spasm, photosensitivity Proph: Ice chips and oral hygiene (mucositis) Loperamide or lotomil (diarrhea) |