Cytotoxic Chemotherapy MOA: prevents cell division by cross linking DNA strands and decreasing DNA synthesis - Cell cycle non specific - Myelosuppresion is generally the dose limiting toxicity Common toxicities: - N/V (mostly acute, often moderately to highly emetogenic) - Myelosuppresion - Alopecia (normally don't see until 3rd cycle) - Sterility / inhertility - Secondary malignancies

Natural products - Cytotoxic Chemotherapy Antitumor antibiotics MOA: block DNA and RNA transcription ADR: cardiotoxicity - CHF - Free radicals from FE -- fibrosis of myocardium - Esp w/ Doxorubicin - RISK of CHF Lifetime max dose

Natural products - Cytotoxic Chemotherapy Antitumor antibiotics MOA: inhibits DNA synthesis only cell cycle specific agent ADR: - Lung toxicity - pulmonary fibrosis, interstitial pneumonitis - Lifetime max 400 units - caution in intubation pt

Anti-neoplastic therapy Flashcards by Samantha Jewers

TNM staging

used for solid tumors

Stage I, II, III, IV

Tumor, nodal status, metastasis

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Adjuvant chemotherapy

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

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Neoadjuvant chemotherapy

giver prior to surgical intervention to reduce tumor size or to remove micrometastases

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Cytotoxic Chemotherapy

Traditional

Toxic to all cells but more specific for rapidly dividing cells

Combination chemotherapy or regimen

Principles

Dose usually bas on body surface area
administered 14, 21, or 28 days most common
Dose density ; want to give same amount of chemo at the same amount of time
Alkylating agents
Antimetabolites
Natural products
Miscellaneous

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Tumor Growth Kinetics

Doubling time
Gompertzian growth

Doubling time
- time needed for a tumor cell population to double in size

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

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Clinically undetectable tumor 10^ ?

Diagnosis possible first symptoms 10^?

Disease symptoms become incapacitating 10^?

10^0 - 10^9 = clinical undetectable

10^9 - 10^11 = diagnosis

10^11 - 10^12 = incapacitating

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Alkylating Agents

Cytotoxic Chemotherapy

MOA: prevents cell division by cross linking DNA strands and decreasing DNA synthesis

Cell cycle non specific
Myelosuppresion** is generally the dose limiting toxicity

Common toxicities:

N/V (mostly acute, often moderately to highly emetogenic)
Myelosuppresion
Alopecia (normally don’t see until 3rd cycle)
Sterility / inhertility
Secondary malignancies

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Cyclophosphamide / Ifosfamide

Alkylating Agents - Cytotoxic Chemotherapy

Hemorrhagic cystitis - due to toxic metabolite acrolein of ifosfamide and cyclophosphamide

Chemo-protection: Mesna binds metabolite

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Cisplatin

Alkylating Agents - Cytotoxic Chemotherapy

Nephrotixicity

Nausea / vomitting (acute and delayed)

Ototoxicity

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Oxaliplatin

Alkylating Agents - Cytotoxic Chemotherapy

Neurpathies

exacerbated by Cold temperatures

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Antimetabolites

Antimetabolite - Cytotoxic Chemotherapy

MOA: structural analogs of naturally occurring substances necessary for specific biochemical reactions

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

most commonly active in the S phase

Common toxicities :

myleosuppression
Mucositis
mild N/V
Diarrhea

Methotrexate (Renal toxicity ; leucovorin rescue for high dose)

Cytarabine (high dose therapy - nervous system toxicity ; ocular irritation - eye drops)

Capecitabine - hand - foot syndrome

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Methotrexate

Antimetabolite - Cytotoxic Chemotherapy

Renal toxicity
Leucovorin rescue for high dose

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Cytarabine

Antimetabolite - Cytotoxic Chemotherapy

High dose therapy ; nervous system (cerebellar) toxicity

Occular irritation - eye drops

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Capecitabine

Antimetabolite - Cytotoxic Chemotherapy

Hand - foot syndrome

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Anthracyclines

Natural products - Cytotoxic Chemotherapy

Antitumor antibiotics

MOA: block DNA and RNA transcription

ADR: cardiotoxicity - CHF

Free radicals from FE – fibrosis of myocardium
Esp w/ Doxorubicin - RISK of CHF

Lifetime max dose

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Mitomycin

Natural products - Cytotoxic Chemotherapy

Antitumor antibiotics

MOA: cross links DNA

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Dactinomycin

Natural products - Cytotoxic Chemotherapy

Antitumor antibiotics

blocks RNA synthesis

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Bleomycin

Natural products - Cytotoxic Chemotherapy

Antitumor antibiotics

MOA: inhibits DNA synthesis only cell cycle specific agent

ADR:

Lung toxicity - pulmonary fibrosis, interstitial pneumonitis
Lifetime max 400 units
caution in intubation pt

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Antitumor antibiotics Toxicities

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Nausea / vomitting

Alopecia

Stomatitis

Myelosuppresion

Myocardiotoxicity: Dose - dependent
- production of toxic free radicals, membrane lipid per oxidation leading to irreversible damage and replacement by fibrous tissue

Microtubule agents

ADR

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ADR:
significant neuropathy**

loss of fine motor control

Microtubule agents - Taxanes

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MOA: prevent microtubule disassembly

ADRs:
hypersensitivity rxn - for both

Neuro, edema (Doxetaxel),

(Paxitaxel) – premedicate
w/ H1/H2 blocker and steroid

Microtubule agents - Vinca alkaloids

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MOA: prevent microtubule assembly

ADRs: Neuropathy, constipation.

DO NOT GIVE VINCRISTINE INTRATHECALLY

Toposisomerase I Inhibitors

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Irinotecan: diarrhea in two phases:

Immediate = anti-cholinergic, treat with atropine.

Delayed, treat with Ioperamide.

Toposisomerase II inhibitors

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Etoposide: causes secondary cancers (AML).

Enyzmes

Asparaginase: | Hypersensitivity reaction, hyperglycemia

Marine based products Eribulin Trabectedin

Eribulin: Microtubule-like agent. Toxicity: peripheral neuropathy Trabectedin: Alkylating-like agent. Toxicity: hand-foot syndrome.

Selective Estrogen Receptor Modulators (SERMs) - tamoxafen

MOA: Inhibits estrogen-R in breast tissue; used in pre-menopause (or post) ADRs: VTE (blood clots -> stroke), endometrial cancer, cataracts, hot flashes

Aromatase inhibitor Letrozole Anastrozole Exemestane

Aromatase Inhibitors (AIs) MOA: Inhibits aromatase enzyme that converts androgen to estrogen Used in post-menopause, preferred over SERMs ADRs: osteoporosis, fractures, arthralgias, CV disease, hot flashes

LHRH Agonists Leuprolide Goserelin Triptorelin

MOA: Negative feedback mechanism: bind testicle, inhibits the pituitary from releasing LH and FSH which stimulates the testis to release testosterone. ADRs: tumor flare: initial tumor growth due to binding to LHRH

LHRH Antagoinsts Degarelix

MOA: Directly inhibits the pituitary from releasing LH and FSH

Antiandrogens

Blocks androgen receptor

Targeted agents

ID certain features of a cancer that make it different from normal cell - prevents tumor cells from entering cell cycle stops cancer growth , doesn't;t kill it

Monoclonal antibodies

- mabs MOA: block antigen on cancer cell surface

Molecularly targeted therapies

blocking signaling inside cell

VEGF-R inhibitor

Molecularly targeted therapies ADR: hypertension, proteinuria, bleeding Hypertension may indicate effectiveness Treat with ACE-I.

EGFR inhibitor

Molecularly targeted therapies Acneiform rash - treat w/ clindamycin and by hydrating. rash may indicate effectiveness

mTOR inhibitors

Molecularly targeted therapies ADR: hyperglycemia, dyslipidemia; caution in diabetes Mucosal ulcers - dexamethasone

BCR-ABL mutation inhibitor.

Molecularly targeted therapies ADR: edema, N/V, neutropenia, cardiac, diarrhea; 3A4 ADRs DOC for CML

CD20

Specific targets ADR: myelosuppression (decrease WBC), infusion reactions

HER2 inhibition

ADR: cardiotoxicity (trastuzumab, pertuzumab) hand-foot syndrome (lapatinib)

Targeted Agents Toxicities

Hair depigmentation Dysphonia Hyperthyroidism

PD-1 and PD-L1 inhibitors Pembrolizumab Nivolumab

Immunological therapies Pembrolizumab: melanoma toxicities - fatigue, itching, rash Nivolumab: melanoma, lung cancer. toxicities - fatigue, malaise

Immunological Therapies

Immunological Therapies Activate immune system to help kill disease, at low tumor burden ADR: fatigue

National Cancer Institute Definition of Cancer

Cancer is a term used for diseases in which abnormal cells divide without control and are able to invade other tissues Cancer is a process rather than specific disease

Cancer Cell Characteristics

- Uncontrolled Cell growth - Ability to invade adjacent structure and/or travel to distant areas - Incapable of physiologic functions of the mature tissue of origin - Altered proteins, enzyme systems, membrane characteristic and cytogenetics

Anti-neoplastic therapy Flashcards

(45 cards)