Therapeutics Exam 2

7 common warning signs of cancer

Δ in bowel/bladder habits

Sore that does not heal

Unusual bleeding or discharge

Thickening or lump

Indigestion/difficulty swallowing

Δ in wart or mole

Nagging cough/hoarseness

Required to diagnose cancer

Tissue exam

Stage 1

localized tumor

Stage 2-3

locoregional disease

Stage 4

metastatic disease

Treatment of choice for most solid tumors in the early stages

Surgery

Used to control/treat local disease & Palliation of symptoms

Radiation

Chemotherapy, Biologic therapy, and Targeted Therapy are all classified as

systemic therapy

Neoadjuvant therapy goal

reduce tumor size, assess response to chemo

Adjuvant therapy goal

treat micro metastatic disease

Goal of metastatic therapy

prolong survival and palliate

Antineoplastic medication

Medication used in the treatment of cancer (chemotherapy, endocrine therapy, targeted therapy, immunomodulators)

Chemotherapy

Cytotoxic medication that has mutagenic, teratogenic, and carcinogenic properties

S-Phase Specific Chemo

Antimetabolites,

Epipodophyllotoxins,

Camptothecins

M-Phase Specific Chemo

Vinca alkaloids, Taxanes

Cell Cycle Nonspecific Chemo

Alkylating agents, Platinum compounds, Antitumor antibiotics

Goal ANC between chemo cycles

>1.5

Goal Plt between chemo cycles

>100000

Tumor-agnostic therapy

uses the same drug to treat all cancer types that have the genetic mutation (change) or biomarker that is targeted by the drug

Pembrolizumab

Microsatellite instability-high or tumor mutation burden- high solid tumors

Dostarlimab

mismatch repair-deficient solid tumors

Larotrectinib and Entrectinib

NTRK gene fusion-positive solid tumors

Chemo doses generally dose via

BSA

CINV Mechanism

Free radical generated release of 5HT from enterochromaffin cells

NT involved in CINV

Serotonin, dopamine, Sub P, Histamine, Acetylcholine

Chemo with high chance of delayed CINV

Cisplatin, carboplatin, cyclophosphamide, doxorubicin

Serotonin (5-HT3) Receptor Antagonists

Ondansetron and palonosetron

AE of Serotonin (5-HT3) Receptor Antagonists

Headache, increased LFTs, constipation, QT prolongation

Neurokinin (NK) 1 Receptor Antagonists

Aprepitant, Fosaprepitant

Neurokinin (NK) 1 Receptor Antagonists are best at preventing

acute and delayed

Agents recommended for highly emetogenic chemo

Neurokinin (NK) 1 Receptor Antagonists

Patient Specific Risk Factors for Acute Emesis

Younger age (

Highly Emetic regimen preferred

Olanzapine 10mg po

Dexamethasone 12mg

Aprepitant

\
then

olanzapine day 2-4

dexamethasone day 2-4

\
\+- lorazepam

Oral chemo high risk regimen

ondansetron

Breakthrough Emesis treatment

treat from another class not tried

myelosupression

\#1 dose limiting side effect of cytotoxic agents

Absolute neutrophil count < 500/mm3

neutropenia

How to treat neutropenia

Colony Stimulating Factors

Colony Stimulating Factors

Filgrastim, Filgrastim-sndz, tbo-Filgrastim, & Pegfilgrastim, Pegfilgrastim-cbqv, Pegfilgrastim-jmdb

\
Sargramostim (Stem cell transplant)

AE of Colony Stimulating Factors

Bone Pain

Allergic Reactions

Pulmonary toxicity in patients receiving bleomycin

Splenic rupture (rare)

Initiation of CSF therapy

24-72 hours after chemotherapy

Consider CSF prophylaxis is risk is

10-20% (always if >20%)

Anemia

Most common hematologic complication of chemotherapy

Anemia treatment options

PRBC transfusions
Erythropoietin stimulating agents

Erythropoietin stimulating agents

Darbepoetin alfa (Aranesp)  - Longer acting

Epoetin alfa (Epogen, Procrit, Retacrit)

Erythropoietin stimulating agents BBW

MI, Stroke, VTE

ESA Hemoglobin @ initiation

Triliciclib

CDK 4/6 inhibitor: protects hematopoietic stem cells from effects of chemo

Only indicated for small cell lung cancer

Triliciclib

Alkylating agents

Cyclophosphamide/Ifosfamide

Cyclophosphamide/Ifosfamide toxicities

**Hemmorrhagic cysititis,** cardiotoxicity, secondary malignancies

Ifosfamide toxicity

CNS toxcitiy,

Encephalopathy

and Hemmorrhagic cysititis

Preventing Hemmorrhagic cysititis

Hydration, Mesna

Treating Hemmorrhagic cysititis

Continuous bladder irrigation

Encephalopathy symptoms

Somnolence, confusion, hallucinations, psychosis

Encephalopathy treatment

methylene blue 50mg q6

Platinum Agents

Cisplatin, Carboplatin, oxaliplatin

Cisplatin toxicities

Severe NV, nephrotoxicity

Cisplatin nephrotoxicity treatment

Pre/Post hydration (1-2 L) w/ normal saline ± diuresis w/ mannitol & K + Mag

Carboplatin Toxicities

severe NV and myelosuppression

Oxaliplatin toxicity

neuropathy, acute and chronic

Antimetabolites

Methotrexate, 5-Fluorouracil,

Cytarabine

Methotrexate MOA

Inhibits dihydrofolate reductase

Methotrexate Toxicities

Myelosuppression, Mucositis, hepato and nephro tox

Methotrexate supportive care

Hydration w/ urinary alkalinization,

D/C penicillins, ASA, probenicid, NSAIDS, Leucovorin rescue

Leucovorin rescue required with

high dose methotrexate

Leucovorin goal MTX level

MTX rescue alternative, reduces quickly

Glucarpidase

5-Fluorouracil toxicities

Hand foot syndrome, myelosuppression

Given to stabilize/strengthen the bond between 5FdUMP and TS

leucovorin

Capecitabine is

5FU

Fluorouracil/Capecitabine antidote

Uridine triacetate (Vistogard)

Low dose cytarabine toxicities

Myelosuppression (DLT)

N/V

Mucositis

High dose cytarabine toxicities

Myelosuppression
Neurotoxicity
Chemical Conjunctivitis

Chemical conjunctivitis treatment

steroid drops

**Anthracyclines**

Doxorubicin
Daunorubicin
Epirubicin
Idarubicin

Intercalates with DNA

Topoisomerase II inhibition

Free radical formation

**Anthracyclines moa**

Anthracycline ADR

Acute/cumulative cardiotoxicity

vesicant

Anthracycline monitoring

baseline EF and lifetime monitoring

Irinotecan toxicity

diarrhea (acute and delayed)

Vincristine ADR

neuropathy

Fatal if given IT

vincristine, vinblastine, vinorelbine

Vinblastine and vinorelbine toxicity

myelosuppression and neurotoxicity

Paclitaxel toxicity

neuropathy, hypersensitivity

Docetaxel toxicity

edema, neuropathy

Cabazitaxel toxcity

diarrhea, neuropathy

what to give with taxanes & epothilone

dexamethasone

Antibody Dependent Cell-Mediated Cytotoxicity

Monoclonal antibody binds to cancer cell
Antibody recruits immune-effector cells (macrophages and NK cells) that can bind to the antibody

Complement Dependent Cytotoxicity

Antigen-antibody reaction activates complement cascade
Production of membrane attack complex and activation of immune response

AntiVEGF mab

Bevacizumab

AntiVEGF mab

Ramucirumab

Bevacizumab

Ramucirumab ADRs

hypertension, proteinuria, GI perforation, wound healing complications, hemorrhage, cardiotoxicity, arterial and venous thrombosis

AntiVEGF targeted therapies

nibs

nib ADRs

Diarrhea, rash, hand-foot syndrome, leucopenia, hypertension, bleeding, wound healing complications, GI perforation, cardiotoxicity, proteinuria, MI, fatigue

Anti-EGFR Therapy

Cetuximab

Panitumumab

Necitumumab

Amivantamab

ADRs Anti-EGFR Therapy

acneiform skin rash, interstitial lung disease, paronychial inflammation, diarrhea, electrolyte depletion (Mg, K, Ca)

Immune Checkpoint Inhibitors ADRs

Immune mediated adverse effects
Colitis, rash, hepatitis, pneumonitis, endocrinopathies

Chimeric Antigen Receptor T Cells (CAR T Cells) ADRs

Cytokine release syndrome, neurologic toxicity

Mucositis prevention

Good oral care, PO cryotherapy Recombinant human fibroblast growth factor (Palifermin)