Pharm 1 Lecture 8: Intro to Oncology

Mesna

treats bladder toxicity from Cyclophosphamide

what drugs cause CIPN (peripheral neuropathy)?

1.Oxaliplatin: for colon cancer

2.Paclitaxel or docletaxel: for breast cancer

Rasburicase

treats high risk tumor lysis syndrome

check G6PD first

levetiracatem

treats seizure from brain metastases

order of Tx for brain metastases: MRI —> dex —> levetiracetam

What opioid preferred for renal impairment?

Hydromorphone (Diaudid) instead of morphine***

What is the most common dose limiting adverse effect?

chemo-induced myelosuppression

What are the common side effects of chemotherapy?

Nausea/Vomiting (N/V) and Myelosuppression.

Trastuzumab, Pertuzumab

HER-2 targeted therapies for HER2+breast, colon, gastric

AE: cardiac toxicity

Cisplatin

CINV, nephrotoxicity, peripheral neuropathy, myelosuppression, ototoxicity

Inhibits DNA synthesis by forming DNA cross-links.

loperamide (Imodium)

antidiarrheal (late) treatment especially caused by Irinotecan

What is the mechanism behind chemotherapy-induced diarrhea?

Increased secretion of electrolytes due to epithelial damage and altered GI motility.

Irinotecan

SE: diarrhea, CINV, neutropenia

Plant alkaloid; it is a Topoisomerase I inhibitor affecting the S and G2 phases of the cell cycle.

Tx: loperamide

What is the role of growth factors in chemotherapy management?

They can help prevent neutropenia, such as Granulocyte colony stimulating factor (G-CSF).

What does 'Dose Dense' refer to in chemotherapy?

A regimen where doses are given more frequently.

What is the most common malignant primary brain tumor in adults?

Glioblastoma (GBM).

What is the preferred management for cerebral edema in brain tumors?

Steroids.

Doxorubicin (Adriamycin), Daunorubicin, Idarubicin, Epirubicin

SE: cardiomyopathy, red urine

MOA: irreversible intercalation into DNA and free radicals

monitoring: CBC, CMP, Echo before, at completion, and 6 months post-treatment.

class: Anthracycline

What is the preferred treatment for surgical candidates with cancer?

Surgical resection

What therapies are considered if a patient is not a surgical candidate or has multiple lesions?

Radiation therapy (WBRT vs. stereotactic radiosurgery)

What is the first-line medication for Chronic Myelogenous Leukemia (CML)?

Imatinib (Gleevec), a TKI

SE: Edema, rash, musculoskeletal pain, nausea/vomiting/diarrhea, myelosuppression

What is the mechanism of action of Imatinib?

Inhibits Bcr-Abl tyrosine kinase, the abnormal gene product of the Philadelphia chromosome

Trastuzumab

blocks HER2 receptors, used in breast cancer

Cardiotoxicity, infusion reactions, pulmonary toxicity, rash, nausea/vomiting/diarrhea

What are some examples of immune checkpoint inhibitors?

Pembrolizumab (Keytruda), Nivolumab (Opdivo), Atezolizumab (Tecentriq)

What are common immune-related adverse events (irAEs) from immunotherapy?

Dermatologic issues, endocrinopathies, diarrhea/colitis, pneumonitis, hepatitis, nephritis

What is the management for Grade 2 immune-related adverse events?

PO Steroids 1-2 mg/kg and consider alternate immunosuppression if persistent

What are Antibody Drug Conjugates (ADCs) used for?

They are used in some first-line approvals and mostly second line for various cancers

What is the mechanism of action for Gemtuzumab Ozogamicin?

DNA-damaging agent targeting CD33

What are Bispecific T-Cell Engagers (BiTEs) used for?

Typically second line or later for heme malignancies and some solid tumors

Cyclophosphamide

SE: hemorrhagic cystitis, myelosuppression,

MOA: cross-link DNA

Treats HER2 breast cancer along with Doxorubicin

Tx: Mesna

Cisplastin

SE: N/V, nephrotoxicity, ototoxicity

MOA: cross-link DNA

Bleomycin, Busalfan

SE: pulmonary fibrosis

MOA: free radical DNA breaks

Oxaliplatin

treats colon cancer

SE: neuropathy (mouth, elbows, knees)

induction, consolidation, maintenance

first therapy/remission

kill residual cells

prolonged/lower intensity

Methotrexate (MTX)

SE: mucositis, myelosuppression

MOA: antifolate

also treats RA

rescue: leucovorin

leucovorin

rescue agent for MTX

Paclitaxel

stabilize microtubules, limiting mvt

SE: sensory neuropathy

premedicate with dexamethazone + H1 + H2

Vincristine, Vinblastine, Vinorelbine

block microtubule assembly

SE: neurotoxicity, constipation

IV only!

Tx for CINV

acute = Ondansetron (5-HT3)

delayed = Aprepitant (NK-1) + Dexamethazone

anticipatory = lorazepam

breakthrough = Olanzapine

Aprepitant (NK1 antagonist) + Dexamethazone

used for delayed CINV

granulocyte colony stimulating factors (G-CSF) prophylaxis

prophylaxis against neutropenia in pts when risk over 20% (65+, previous chemo or radiation, open wounds, poor nutrition, HIV)

chemo-induced neutropenia

ANC < 1500 cells/microL. Severe is ANC < 500 cells/microL.

Tx: hand hygeine, G-CSF prophylaxis for high risk

Tx if febrile: blood cultures then IV antipseudomonal B-lactam + Vancomycin if MRSA

febrile neutropenia

ANC < 1500 plus fever

blood cultures then IV antipseudomonal B-lactam + Vancomycin if MRSA

Tx for hypercalcemia of malignancy

1.IV normal saline

2.calcitonin (fast)

3.zoledronic acid (lasting)

4.Denosumab (refractory)

Tx for tumor lysis syndrome

1.hydrate

2.allopurinol (blocks uric acid formation to decrease AKI)

3.Rasburicase (if high risk, CI in G6PD deficiency)

Tx for brain metastases

Sx: new seizure

Tx:

1.urgent imaging

2.Dexamethazone

3.Levetiracetam (after seizure only)

*avoid carbamazepine and phenytonin

Tx for malignant spinal cord compression

1.Dexamethazone

2.MRI
3.radiation oncology + neurosurg

5 main opioids used in chemo

Morphine: CI in CKD

Oxycodone

Hydromorphone: preferred in CKD

Fentanyl: not rapid, CI in opioid-naive pts

Methadone: SE of QT prolongation

*Do NOT use Meperidine

converting from one opioid to another on chemo

calculate equianalgesic doses

if pain well controlled: reduce by 25-30%

if pain not well controlled: start at 100%