Anti-neoplastic Therapy Flashcards by Sara Sverker

What are the four cancer cell characteristics?

Uncontrolled cell growth
Ability to invade adjacent structures and/or travel to distant areas
Incapable of physiologic functions of the mature tissue or origin
Altered proteins, Enzyme systems, membrane characteristics, and cytogenics

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What are the different anti-cancer therapies?

Cytotoxic therapies
Anti-hormonal therapies
Targeted therapies
Immunotherapy
Blood and bone marrow transplant

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What is adjuvant chemotherapy?

Given after surgery to reduce the risk of local and systemic recurrence

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What is neoadjuvant chemotherapy?

Given prior to surgical intervention to reduce the tumor size or to remove micrometastases

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What is cytotoxic chemotherapy?

Traditional treatment

Toxic to all cells but more specific for rapidly dividing cells like those found in the GI tract, Hair, and bone marrow

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What are the agents classified as cytotoxic chemotherapy?

Alkylating agents
Antimetabolites
Natural Products
Misc.

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What are the three tumor growth kinetics?

Doubling time
Gompertzian Growth
Log-kill hypothesis

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What is doubling time of the tumor growth?

Time needed for a tumor cell population to double in size

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What is Gompertzian tumor growth?

Early growth is exponential, but as tumor gets bigger, growth slows due to decreased nutrients/blood supply

Small tumors grow faster, larger tumors grow slower

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What is log-kill hypothesis?

A given dose of chemotherapy kills the same fraction of tumor cells regardless of the size of the tumor at the time of treatment

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What are the principles of cytotoxic chemotherapy?

Combination chemotherapy or regimen
Good single agent activity against tumor
Different MOAs
Different toxicities or different onset of toxiticites
Maximum cell kill within toxic limits
Different mechanisms of action to target a cancer cell in different ways
Decrease drug resistance
Dosing
Administration

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What is the dosing principle for cytotoxic chemotherapies?

Dose based on body surface area (BSA)

Use actual weight

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What is the administration principles of cytotoxic chemotherapies?

Cycles every 14, 21, or 28 days most common
Cycling or rotating differetn combinations may be done to decrease resistance
Dose intensity and dose density

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What is NATER?

point at which neutrophils are lowest in the body usually 7-10 days after patient receives chemo and normal levels are reached again by day 21

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What is the MOA of alkylating agents?

Prevents cell division by cross-linking DNA strands and decreasing DNA synthesis

Cell-cycle non specific

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What are the toxicities of alkylating agents?

Myelosuppression
N/V = acute; moderate to high severity
Alopecia
Sterility/infertility
Secondary malignancies

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Which three alkylating agents are lipophilic and typically used to treat brain tumors?

Carmustine
Lomustine
Procarbazine

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What are the toxicities of Cyclophosphamide/Ifosfamide?

hemorrhagic cystitis due to acrotein metabolite

Treat with mesna

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What is the toxicity of Cisplatin?

Nephrotoxicity
N/V
Ototoxicity

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What is the toxicity of Oxaliplatin?

Neuropathies that are exacerbated by the cold

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What are antimetabolites?

Structural analogs of naturally occurring substances necessary for specific biochemical reactions

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What is the MOA of antimetabolites?

Compete with normal metabolites
falsely insert themselves for a metabolite normally incorporated into DNA and RNA

Active in S phase

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What are the toxicities of antimetabolites?

Myelosuppression
Mucositis
Mild N/V
Diarrhea
Renal toxicity
CNS toxicity
Hand foot syndrome

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What is the toxicity of methotrexate?

Renal toxicity

Use leucovorin to treat/replenish folate

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What is the toxicity of cytarabine?

High dose therapy causes nervous system toxicity | Occular irritation = treat with eye drops

What enhances efficacy of Fluorouracil?

Leucovorin

What is the toxicity of capecitabine?

hand-foot syndrome

What are the natural products?

Antitumor antibiotics Plant alkaloids = vinca alkaloids, taxanes, topoisomerase I and II Marine based products Enzymes

What are the antitumor antibiotics?

Anthracyclines Mitomycin Dactinomycin Bleomycin

What is the MOA of anthracyclines?

block RNA and DNA transcription

What is the MOA of mitomycin?

Cross-links DNA

What is the MOA of Dactomycin?

Blocks RNA synthesis

What is the MOA of Bleomycin?

inhibits DNA synthesis

What are the toxicities of Antitumor antibiotics?

N/V Alopecia Stomatitis Myelosuppression Bleomycin = Lung toxicity/pulmonary fibrosis/interstitial pneumonitis CARDIOTOXIC/congestive heart failure = anthracyclines Dose dependent myocardiotoxicity

What is the lifetime limit for dose of antitumor antibiotics?

450 In kids its 300

What is the dose dependent myocardiotoxicity of antitumor antibiotics?

Produces toxic free radicals, membrane lipid peroxidation leading to irreversible damage and replacement by fibrous tissue Risk factors include cumulative dose, patient age, concomitant chemotherapy with known cardiotoxicity, and radiation therapy Can have early toxicity within 3 months of completion or late toxicity decades later Treat with Dexrazoxane

What is the MOA of Dexrazoxane?

EDTA-like chelating agent, binds intracellular iron released following lipid peroxidation

What are Mictrotuble agents?

Synthetic and semi-synthetic Different MOAs Taxanes and Vinca alkaloids

What are the toxicites of taxanes?

Neuropathies Peripheral edema Hypersensitivity reactions = especially Paclitaxel; premedicate with H1, H2 blocker and steroids

What are the toxicites of vinca alkaloids?

Neuropathies Constipation DO NOT GIVE INTRATHECALLY = Vincristine

What are the toxicities of Topoisomerase I?

DIARRHEA = immediate and delayed reaction ( I ran to the can)

What are the toxicities of Topoisomerase II?

Secondary cancers

What are the toxicities of Enzymes?

Hypersensitivity reaction Hyperglycemia Pancreatitis Coagulopathies

What are the two marine based natural products?

``` Eribulin = sea sponge Trabectedin = sea squirt ```

What is the MOA and toxicities of Eribulin?

Microtubule like agent Fatigue Peripheral Neutropathy Chemotherapy induced N/V Myelosuppression

What is the MOA and toxicities of Trabectedin?

like an alkylating agent ``` Fatigue Hand-foot syndrome CINV Hepatic damage Myelosuppression ```

What is hormonal therapy?

Blocks production of hormones or hormone receptors in the body

What are the types of hormone therapy?

Anti-estrogens Anti-androgens Luteinizing hormone releasing hormone analogs

What are SERMs used in?

Premenopausal diseases

What are aromatase inhibitors used in?

Postmenopausal diseases

What is the benefit of using SERMs in hormonal therapy?

increased 15 year survival rate

What are the ADRs of SERMs?

Cataracts Endometrial cancer VTE DDI with antidepressants

What are the ADRs of aromatase inhibitors?

Osetoporosis Fractures Arthralgias

What are LHRH agonists for hormonal therapy?

inhibit the pituitary from releasing LH and FSH which stops stimulation of the testes to produce testosterone First line treatment for prostate cancer

What is the ADR of LHRH agonists?

Tumor flare

What are LHRH antagonist?

Directly inhibit pituitary from releasing LH and FSH

What are antiandrogens?

Blocks antigen receptor

What is the MOA of targeted therapies?

identifies certain features of a cancer cell taht make it different from the normal cell Prevent tumor cells from entering cell cycle ro target signals that trigger cancer growth, metastasis, and immortality

What are the targeted agents?

Monoclonal antibodies | Molecularly targeted therapies

What is the MOA of monoclonal antibodies?

Antibodies that match an antigen on the cancer cell surface

What is the MOA of molecularly targeted therapies?

block signaling inside the cell

What are the toxicities of VEGF signaling pathway inhibitors?

Hypertension Proteinuria Bleeding Imparied wound healing

What is the toxicity of EGFR inhibitors?

Acneiform rash

What are the toxicities of mTOR inhibitors?

``` Hyperglycemia Dyslipidemia Mucosal sensitivity Ulcers = usually only one; treat with deamethasone swish and spit CYP 3A4 DDIs ```

What are the toxicities of BCR-ABL mutation inhibitors/

``` Edema N/V Neutropenia Fatigue Cardiac Diarrhea CYP3A4 DDIs ```

What do CD20 specific target therapies attack and what are their toxicities?

B cells Infusion reactions Myelosuppression

What are the toxicites of HER2 inhibition?

``` CARDIOTOXICITY N/V Fatigue Diarrhea Hand-foot syndrome DDIs with strong 3A4 inducers/inhibitors ```

What are the targeted agents toxicities?

Monoclonal Antibodies have potential hypersensitivity reactions based on mAb origin ``` QT prolongation Neuropathy Colitis Fatigue Hair thinning Low grade N/V and myelosupression HAIR DEPIGMENTATION DYSPHONIA HYPOTHYROIDISM (does not reverse) ```

What are the immunological therapies?

``` Interferon Interleukin Lenalidomide Thalidomide CTLA-4 inhibitors PD-1/PDL-1 inhibitors Cancer vaccine ```

What are the immunological therapies toxicities?

``` Fatigue Itching Rash Malaise Pneumonitis ```

What are the types of Bone marrow transplants?

Autologous - high dose with stem cell rescue Allogeneic Nonmmyeloablative

What are the sources of stem cells?

Bone marrow Peripheral blood Cord blood