Chemotherapy Toxicities

Which drugs cause myelosuppression? Which don’t?

All chemotherapy drugs except bleomycin, pegasparagase, and vincristine

What is the nadir?

The lowest point that WBCs and platelets reach, usually occurs at 7-14 days

Cutoffs for neutropenia and severe neutropenia for ANC

Neutropenia <1000 cells/mm3

Severe neutropenia <500 cells/mm3

Granulocyte Colony-Stimulating Factors - MOA and Drugs and Dosing Frequency

• Stimulate WBC production in the bone marrow.

• Given prophylactically after chemotherapy to reduce the duration and severity of neutropenia

• Filgrastim (Neupogen) - Daily

• Pegfilgastrim (Neulasta) - Once per chemo cycle

Granulocyte Colony-Stimulating Factors - Side effects and Monitoring

Side effect: Bone pain, splenic rupture

Monitoring: CBC with diff, upper abominal pain

Store in refridgerator

Administer first dose no sooner than 24 hours AFTER chemo start

Febrile neutropenia diagnostic criteria

Fever: Temp >= 38.3C (101F) or 38C for 1 hour
Neutropenia: ANC <500

When to start empiric antibiotics for febrile neuotropenia?

For all patients with febrile neutropenia

When to give platelet transfusion for thrombocytopenia?

When platelets reach <10,000 cells/mm3

When to give erythropoiesis-stimulating agent (ESA)?

• Patient has a non-myeloid malignancy (e.g., carcinoma, sarcoma) and anemia is due to the effect of myelosuppressive chemotherapy.

• Hgb is < 10 g/dL and there is a minimum of two additional months of planned chemotherapy.

• The lowest dose needed to maintain a Hgb level sufficient to avoid RBC transfusions is used.

ESA's can shorten survival and increase tumor progression —> not recommended in patients receiving chemotherapy with curative intent

What drugs most commonly cause chemotherapy-induced nausea and vomiting?

Cisplatin, carboplatin, cyclophosphamide, and anthracyclines

Classes of antiemetics for CINV

Antiemetic regimens for: High emetic risk (cisplatin, antracycline, and cyclophosphamide)

3-4 drugs

• Preferred: NK1 RA + 5-HT3 RA + olanzapine + dexamethasone

• OR NK1 RA + 5-HT3 RA + dexamethasone

• OR Palonosetron + olanzapine + dexamethasone

NK1 RA example (aprepitant)

Antiemetic regimens for: Moderate emetic risk

2 or 3 drugs

• NK1 RA + 5-HT3 RA + dexamethasone

• 5-HT3 RA + dexamethasone

• Palonosetron + olanzapine + dexamethasone

Antiemetic regimens for: Low emetic risk

1 drug

• 5-HT3 RA (dolasetron, granisetron or ondansetron)

• Dexamethasone

• Metoclopramide

• Prochlorperazine

Substance P/Neutokinin01 Receptor Antagonists (NK1 RAs) - Drugs

• Aprepitant (Emend)

• Fosaprepitant (Emend) - IV

5-HT3 Receptor Antagonists - Drugs, Warnings, Side effects

• Ondansetron (Zofran)

• Ganisetron (Sancuso)

• Palonestron (Aloxi)

• Warnings: Dose dependent QT prolongation (limit IV Zofran to 16 mg); Serotonin syndrome

• Side effects: Headache, constipation

Dopamine Receptor Antagonists - Drugs

• Olanzapine (Zyprexa)

• Prochlorperazine

• Promethazine

• Metoclopramide (Reglan)

• Haloperidol (Haldol)

Cannabinoids - Drug and extras

Dronabinol

• Marinol capsules C3

• Syndros solution C2

Extravasation management - Anthracyclines

apply cold compresses and administer dexrazoxane or topical dimethyl sulfoxide (DMSO)

Extravasation management - Vinca alkaloids

apply warm compresses and administer hyaluronidase

Vaccination notes

Avoid all vaccinations during chemotherapy

When planned, vaccination should precede chemotherapy by 2 or more weeks

What problems can tumor lysis syndrome cause?

• Hyperkalemia - arrhythmias

• Hyperphosphatemia

• Hypocalcemia - anorexia, nausea, seizures

• Hyperuricemia - Can damage kidneys

• Acute renal failure - due to hyperuricemia or phosphate accumulation

Drugs used for prevention of TLS? How to treat?

• Allopurinol (higher doses than gout (400-800 mg/day))

• Febuxostat

• Rasburicase if severe

Treatment of hypercalcemia of malignancy and MOA

• Hydration with NS

• IV bisphosphates - inhibits bone reporting by stopping osteoclast function

• Zoledronic acid - inhibits bone reporting by stopping osteoclast function

• Pamidonate - inhibits bone reporting by stopping osteoclast function

• Calcitonin (Miacalcin - inhibibs bone resorption, increase renal calcium excretion

• Denosumab (Xgeva) - RANKL