Oncology (Chemo Agents) Flashcards by Brianna Katzman

Pediatric Treatment Principles (3)

Curative if at all possible
Get more Chemo than adults
Prevent long term complications

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Dosing for anti-neoplastic agents

BSA is the standard for individualized based dosing

Mosteller Equation*****

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Mosteller Equation

BSA = (ht*wt)/3600
ALL UNDER Sq root

ht = cm
wt = kg

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Other options for dose adjustments (4)

mg/m2
Units/m2
g/m2
Weight (kg) is sometimes used
o	Often used in children < 1 year of age

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Corticosteroids (3)

Prednisone
Dexamethasone
Methylprednisone

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Corticosteroids MOA

promotes decrease in lymphocytic cell lines

One of the mainstays, especially in Leukemia

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Corticosteroids Side Effects (6)

Symptoms resolve by…

Hyperglycemia: May even require insulin while they are on the steroids
Fluid retention, facial swelling
Increased appetite (helps with nausea during induction)
Hypertension – Watch BP
Mood changes: Especially in children; children can get very cranky on steroids
Risk of GI ulcers

Symptoms typically resolve once treatment stops (typical duration of therapy is about 50 days)

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Corticosteroids Special Considerations

Patients should be on acid suppression with a proton pump inhibitor or H2 receptor antagonist to protect against ulcers

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Corticosteroids - tx of side effects (2)

Monitor blood pressure

Monitor blood sugar

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Corticosteroids

What steroid is better at penetrating the spinal fluid?

Dexamethasone penetrates spinal fluid tissue better than prednisone

Choice of steroid however depends on the protocol

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Alkylating Agents (4)
MOA

Cell cycle

Highly reactive compounds

MOA - forms covalent (tight) bonds within DNA which leads to interference in cell replication

Cell cycle non-specific: Good thing

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Common alkylating agents used in Pediatrics (3)

Cyclophosfamide
Ifosfamide
Busulfan

Used in pediatrics but more for bone marrow transplant conditioning

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Less Commonly Used Alkylating agents in pediatrics (2)

o Decarbizine

o Temozolamide

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Cyclophosfamide (Alkylating Agent)

Activated where?

Prodrug, must be activated in the liver to the active compound (CYP2B6 to 4-HC)

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Cyclophosfamide (Alkylating Agent)
Dosage forms (2)

IV doses used for cancers

PO used for other indications (FDA improved for minimal change disease in children)

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Cyclophosfamide (Alkylating Agent)
Side Effects (7)

Hemorrhagic cystitis (high doses require treatment with mesna): Leads to severe bleeding
Myelosupression: Since these agents cause bone marrow suppression, other non-cancer rapidly diving cells (ex: bone marrow, epithelial cells) will be affected
N/V (acute and delayed)
SIADH (Syndrome of Inappropriate Anti Diuretic Hormones)
Nasal stuffiness (decreases with infusing at least over 1 hr)
Pulmonary and cardiotoxicity
Alopecia

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Cyclophosfamide (Alkylating Agent)
Special Considerations(3)

Doses > 1800 mg/m2 should be infused over 1 – 6 hrs

Typical hydration with higher doses is 125 ml/m2/hr (D5 1/2NS)

Monitor UOP
Urine specific gravity (SG) must be < 1.01 prior to initiating the infusion and maintain urine SG < 1.01 (test urine with each void)
o Should be in IVF during infusion

Ifosamide

Metabolized by?

Prodrug, must be metabolized to the active form (by CYP 3A4)

Ifosamide

Dosage form

Ifosamide
Side effects (7)

Neurotoxicty - requires neuro checks with infusions: See enceophalopathy, hallucinations, coma

Hemorrhagic cystitis - urine checks while on therapy is important

Nephrotoxicity: Fanconi syndrome due to renal tubular damage

Peripheral neuropathy

Cardiotoxicity – dose dependent

Interstitial pneumonitis, pulmonary fibrosis

Marrow supression, alopecia

Ifosamide
Drug Interactions (4)

Metabolized to the active form by CYP3A4

Inhibitors = less effective, inducers = > risk of toxicity

Anything that inhibits CYP3A4 will inactive this drug

If you give something that upregulates CYP3A4 you will see increased effects of this drug

Hemorrhagic cystitis

What is it

Inflammation and damage to bladder epithelium leading to hematuria. Also can cause pain and irritation as well as long-term damage
o Caused by the metabolite, acrolein

Hemorrhagic cystitis

How can it be avoided?

At higher doses mesna can be given to bind to the metabolite and limit the exposure to the bladder

Maintain good hydration

Hemorrhagic cystitis

Tx (3)

Increase mesna dosing to 100% ifosfamide dose

Maintain good hydration

Sometimes patients may require bladder irrigations to washout the chemical

Mesna | MOA

Binds to the urotoxic metabolites (acrolein and 4-hydroxyifosfamide) of ifosfamide and cyclophosphamide (to a lesser extent)

With ifosfamide doses _____ mesna should be administered

> 1.2 g/m2 * 60 – 100% of ifosfamide dose * Up to 6% will still develop urotoxicity with mesna

Why do we use mesna?

to prevent bladder toxicity from ifosfamide and cyclophosfamide

Dacarbazine (DTIC) Used for Dosage form Side effects(2)

Used for solid and heme malignancies Dosage form: IV only Similar side effects to other alkylating agents o Myelosuppression o N/V

Temozolamide (Temodar®) | Benefit

Newer alkylating agent Benefit = PO administration o IV formulation is available but used less o Metabolized the active decarbazine

Temozolamide (Temodar®) | FDA approved for (2)

FDA approved for glioblastoma and refractory astrocytoma therapies.

Temozolamide (Temodar®) Studied in children with... (2)

Studied in children for meduloblastoma, PNS tumors

Platinum Alkylating Agent MOA (3) Cell phase... Contains...

o Mechanism Forms a covalent (strong) bond with DNA, platinum compound bound to DNA leads to inability for the cell to repair the DNA and ultimately cell death - Contain heavy metal (platinum) - Cell phase non-specific

Platinum Alkylating Agent | Toxicity

• Toxicity – lots! Remember there will be a lot of toxicity with these

Platinum Alkylating Agent | • Commonly used agents in pediatrics

o Cisplatin | o Carboplatin

Cisplatin (Platinum Alkylating Agent) Dosage form Side effects (6)

• Dosage form: IV - Nephrotoxicity -- Renal tubular nephropathy - associated with cation wasting (watch Mg, Na, and K)Requires aggressive hydration & high urine output - Prolonged myleosupression, thrombocytopenia - Hepatotoxicity - Peripheral neuropathy: Give Gabapentin for this pain -- In general Gabapentin is given for the pain associated with alkylating agent side effect pain - Nausea and vomiting – see delayed nausea - Ototoxicity

Cisplatin (Platinum Alkylating Agent) | Administration

Should be given with aggressive hydration – fluids should contain K+ and Mg+

Carboplatin (Platinum Alkylating Agent) Dosage form Special Considerations (2)

Dosage Form: IV -- Usually dosed based on BSA or AUC Special Considerations - Cleared vis renal excretion, so good kidney function is essential with hydration - Delayed nausea so dexamethasone can be used with anti-emetic regimen (unless otherwise contraindicated)

Carboplatin (Platinum Alkylating Agent) Side effects are similar to cisplatin (2)

Notable exceptions… - Less emetogenic, nephrotoxic, and neurotoxic - More myelosupressive

S phase specific drugs (2)

cytosine arabinoside | hydroxyurea

S Phase specific - self-limiting (2)

6-mercaptopurine | methotrexate

M phase specific drugs (3)

vincristine vinblastine paclitaxel

Cycle non-specific drug (6)

``` alkaylating agents nitrosources antitumor antibiotics procarbazine cisplatin dacarbazine ```