Therapeutics Iv, Exam Iv

Front 1

Cancer

(Definition)

Back 1

A group of diseases:

1.) uncontrolled cellular growth

2.) local tissue invasion

3.) distant metastases

Front 2

Most commonly diagnosed cancer in men?

Back 2

Prostate

Front 3

Most commonly diagnosed cancer in women?

Back 3

Breast

Front 4

Most common cause of cancer death in women?

Back 4

Lung

Front 5

Most common cause of cancer death in men?

Back 5

Lung

Front 6

Age group for which cancer is the leading cause of death?

Back 6

> 85 years of age

Front 7

Lifetime probability of developing cancer for men and women?

Back 7

men = 1 in 2

women = 1 in 3

Front 8

Top 3 causes of cancer death in children and adolescents?

Back 8

0-14 years: 1.) Brain, 2.) Leukemia, 3.) Soft Tissue

15-19 years: 1.) Leukemia, 2.) Bone/Joints,

3.) Brain

Front 9

The 2 major influences in the development of cancer in Americans?

Back 9

1.) Cigarette smoking

2.) Age

Front 10

Obesity is a risk factor for which 3 cancers?

Back 10

1.) Colon

2.) Prostate

3.) Ovarian

Front 11

What lack in diet is associated with higher rates of cancers?

Back 11

5 or more servings of vegetables daily

Front 12

4 Processes in Carcinogenesis

Back 12

1.) Initiation

2.) Promotion

3.) Conversion

4.) Progression

Front 13

Initiation

(Definition)

Back 13

irreversible damage to normal cells caused by exposure to carcinogenic substances

Front 14

Promotion

(Definition)

Back 14

carcinogens alter the environment to favor growth of the mutated cells

possibly reversible

Front 15

Conversion

(Definition)

Back 15

the transformation of a normal cell to a cancerous cell

may take 5-20 years

Front 16

Progression

(Definition)

Back 16

further genetic changes leading to increased cell proliferation

Front 17

Angiogensis

(Definition)

Back 17

the development of new blood vessels by the tumor in order to grow

Front 18

Who do we screen for cancer?

Back 18

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

Front 19

Describe the screening schedule for breast cancer.

Back 19

Clinical Breast Exam:

- starting at age 20

- at least every 3 years, then annually prior to mammograms

Mammogram:

- starting at age 40

- annually

Front 20

Describe the screening schedule for cervical cancer.

Back 20

Pap Smear:

- starting at age 21 to 29

- every 3 years

HPV and Pap Tests:

- starting at age 30 to 65

Front 21

Describe 5 screening schedules that both men and women should follow starting at age 50.

Back 21

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

Front 22

Goals of Cancer Treatment

Back 22

1.) Cure

2.) Prolong Life

3.) Palliation

Front 23

Adjuvant Therapy

(Definition)

Back 23

systemic therapy that is administered to treat any existing micrometastases remaining after surgical excision of localized disease.

Front 24

Neoadjuvant Therapy

(Definition)

Back 24

treatment given prior to the definitive local treatment, usually prior to surgery.

Front 25

What order of kinetics do cancer treatments follow?

Back 25

1st order

(cancer drugs kills a constant proportion of tumor cells)

Front 26

What kind of cells do most cancer treatments target?

Back 26

Rapidly proliferating cells, whether cancerous or no. (Ex: mucus membranes, hair follicles, bone marrow)

Front 27

How are cancer treatments dosed?

Back 27

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.

Front 28

Gompertzian Growth Curve-Log-Kill Hypothesis

Back 28

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

Front 29

Why Combination Chemotherapy?

Back 29

1.) Maximal cell kill within tolerated toxicity

2.) Broader range of coverage

3.) Prevent development of resistant lines

Front 30

Metronomic Therapy

(Definition)

Back 30

For molecularly-targeted drugs only.

Taken continuously until disease progression or unacceptable adverse events occur.

Front 31

4 Classes of DNA-Damaging Drugs

Back 31

1.) Alkylating Agents

2.) Antibiotics

3.) Topoisomerase Inhibitors

4.) Anti-Metabolites

Front 32

Characterization of DNA-Damaging Drugs

Back 32

Interfere with transcription and reduplication

- Affected cells undergo cell cycle arrest and apoptosis

* Mutagenic, Teratogenic, and Carcinogenic

Affect rapidly proliferating cells

Front 33

Alkylating Agents

(Mechanism of Action)

Back 33

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

Front 34

8 Alkylating Agents

Back 34

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 *

Front 35

Nitrogen Mustards

Back 35

1st Gen: Mechlorethamine *, N-0xide

2nd Gen *: Chlorambucil, Melphalan, Bendamustine, Spiromustine

3rd Gen: Uramustine

Steroid-Coupled: Estramustine phosphate, DHEA mustard, Prednimustine

Phosphoramide *: Cyclophosphamide, Ifosfamide

Front 36

Which nucleotide is most susceptible to alkylation?

Back 36

Guanine

Front 37

Phosphoramide Mustards

(Mechanism of Action)

Back 37

Prodrugs metabolized by CYP450 to phosphoramides and acrolein

Phosphoramides alkylate DNA

Acrolein alkylates proteins (AE: Bladder Toxicity)

Front 38

Cyclophosphamide

(Cytoxan)

Back 38

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

Front 39

Ifosfamide

(Ifex)

Back 39

Uses: sarcomas, testicular cancer, lung cancer

AE: *hemorrhagic cystitis (Mensa mandatory)

Front 40

Nitrosoureas

(Mechanism of Action)

Back 40

Carmustine (BiCNU), Lomustine (CeeNU), Streptozocin (Zanosar)

Lipid Soluble, often oral dosing, long nadir

Front 41

Carmustine

(BiCNU)

Back 41

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

Front 42

Lomustine

(CCNU, CeeNU)

Back 42

Uses: primary brain tumors

Dosage Forms: oral capsule (10 mg increments)

Long time to nadir (dose every 6 weeks)

Front 43

Platinum Compounds

(Mechanism of Action)

Back 43

Crosslink DNA like mustards

- intrastrand (bind twice, same strand)

- interstrand (bind twice, crosslink)

- monoadduct (bind once)

- intermolecular (bind to DNA and protein)

Front 44

Cisplatin

(Adverse Effects)

Back 44

Nephrotoxicity

Nausea/Vomiting (acute and delayed)

Neuropathy

Myelosuppression (slight)

Ototoxicity

Front 45

Carboplatin

(Adverse Effects)

Back 45

Uses: broad spectrum

AE: nephrotoxicity, ototoxicity, neuropathy, N/V

(less than cisplatin)

myelosuppression

DLT: Thrombocytopenia

Front 46

Carboplatin

(Dosing)

Back 46

Calvert Formula

Target AUC (6mg/mL/min) * [GFR + 25]

(25 = constant representing non-renal Cl)

Front 47

Oxaliplatin

Back 47

Uses: colorectal cancer, GI tumors

Often used in combo with 5-FU or Capecitabine

Dose: 135 mg/m^2

Front 48

Oxaliplatin

(Adverse Effects)

Back 48

Hypersensitivity rxn

*DLT: Neurotoxicity (acute and delayed)

Nephrotoxicity

Fatigue

Myelosuppression

N/V/D

Pulmonary Fibrosis *rare

Front 49

Oxaliplatin

(DLT elaborated)

Back 49

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)

Front 50

Oxaliplatin

(N/V tx)

Back 50

5-HT3 antagonist (setron drug) + dexamethasone

(ex: Ondasetron, Granisetron, Palonosetron, Dolasetron, Metaclopramide)

Front 51

Busulfan

(Myleran)

Back 51

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)

Front 52

2nd Gen Nitrogen Mustards

Back 52

Chlorambucil, Melphalan, Bendamustine

More stable with inclusion of 6-member ring and long hydrocarbon/carboxyl tail

Front 53

Chlorambucil

(Leukeran)

Back 53

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

Front 54

Melphalan

(Alkeran)

Back 54

Uses: multiple myeloma, BMT

Dosage Forms: oral and IV

9 mg/m^2 PO x4-7 days Q4-6 weeks

(BMT = 100 mg/kg)

Front 55

Bendamustine

(Treanda)

Back 55

Uses: Chronic lymphocytic leukemia (CLL), non-Hodgkin's Lymphoma (NHL)

AE: bone marrow suppression, N/V, pyrexia

(more than chlorambucil)

Front 56

Topoisomerase Inhibitors

(Mechanism of Action)

Back 56

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

Front 57

Irinotecan

(Camptosar)

Back 57

Camptothecin (T1)

Uses: Colorectal cancer

AE: Diarrhea (acute and delayed), neutropenia (dose dependent), N/V, dehydration, alopecia, mucositis, acute pulmonary toxicity?

Front 58

Irinotecan

(Diarrhea tx)

Back 58

Acute:

- atropine 0.25 - 1 mg IVP

Delayed:

- loperamide 4 mg PO LD, then 2 mg PO Q2h ATC until resolved for 12 hours

Front 59

Etoposide

(VP-16, Vepesid)

Back 59

Epipodophylotoxin (T2)

Uses: Lung cancer, NHL, BMT

Dosage Form: in EtOH, IVPB (hypotension), 50 mg PO capsules (F= 50%)

Front 60

5 Classes of Antitumor Antibiotics

Back 60

1.) Cyclopropylpyrroloindole

2.) Minor-Groove DNA-binding

3.) Aminoquinone

4.) Polycyclic Aromatic (anthracyclines)

5.) Enediyne

Front 61

2 Broad Classes of Antitumor Antibiotics

Back 61

1.) Alkylate DNA

(Cyclopropylpyrroloindoles, minor groove

binding, aminoquinones)

2.) Redox Cycling

(Polycyclic aromatics, enediynes)

Front 62

Redox Cycling Antibiotics

(Class Adverse Effects)

Back 62

Cardiotoxicity

Front 63

Bleomycin

(Blenoxane)

Back 63

4 different proteins from bacteria

Uses: testicular, NHL, head/neck cancers

AE: pulmonary toxicity, pyrrexia, mucositis

Front 64

Polycyclic Aromatics

(aka Anthracyclines)

Back 64

Doxorubicin, Amrubicin, Epirubicin, Valrubicin, Pirarubicin, Berubicin

MOA: intercalates between DNA base pairs and generates free oxygen radicals using the carbonyls on its B ring

Front 65

Doxorubicin

(Adriamycin)

Back 65

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

Front 66

Dexrazoxane

(Zinecard)

Back 66

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

Front 67

Mitozantrone

(Novantrone)

Back 67

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

Front 68

Anti-Metabolites

(Classes and Subclasses)

Back 68

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

Front 69

Anti-Metabolites

(Mechanism of Action)

Back 69

1.) Serve as false building blocks

2.) Inhibit synthesizing enzymes

- prevent synthesis of DNA and RNA

Non-selective, therefore best localized

Front 70

Methotrexate

(Trexall, Rasuvo)

Back 70

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

Front 71

Methotrexate

(Adverse Effects + Risk Factors)

Back 71

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

Front 72

Methotrexate

(Monitoring)

Back 72

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

Front 73

Fluorouracil

(5-FU)

Back 73

Uses: GI tumors, colorectal cancer, pancreatic

2nd line in breast, lung and head/neck

Dose: 500-1000 mg/m^2 IVP or 24H CIVI

Front 74

Fluorouracil

(Adverse Effects)

Back 74

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)