Principles of Cancer Management II

Systemic anticancer with or without radiation, no surgery possible

A therapy trying to eradicate cancer cells

Dissapearance of cancer signs (as far as we can tell)

Eradicate any remaining disease (like adjuvant therapy) after complete remission. Used after induction therapy.

Prevent cancer from recurring or maintain response

Extravasation, where the toxic drug can leak out of the veins and cause toxicity in surrounding tissues

Often used for drugs that can't cross the BBB
Can be given as a spinal injection or into the ommaya reservoir (an implant under the skin going into the skull)
3-15mL total volume, even less for ommaya reservoir
They must be preservative free (no benzyl alcohol) to avoid seizures
Must remove volume from CSF equal to amount of drug injected

With a lumbar puncture, it is very painful, requiring consious sedation or general anethesia, and the patient ususally has to lie down for about 30 minutes, which can be very inconvenient with frequent administration. Ommaya reservoir makes this much easier.

They are dosed based upon AGE

Once a patient is 3 years old, they have the same amount of CSF as a full grown adult, so dosing changes up to age 3 and then is constant.

It used to be given in the same room as IT administrations, and when given accidentally IT it was lethal. Now given via IV piggyback bags to avoid confusion, and no non-IT drugs are allowed into the same room where an IT administration is being given anymore.

Black box warning on vincristine, fatal if not given IV

Weight: monoclonal antibodies and CAR-T therapy
BSA: Cytotoxic chemotherapies
Fixed dose: Small molecule orally administered agents

Carboplatin- using the calvert equation
Therapeutic drug levels

BSA is not accurate for patients under 15kg, so for anyone under 15kg, dose based on weight even if the patient would normally be dosed based on BSA

For most chemotherapy drugs, weight based dosing in obese patients still uses actual body weight, no adjustments necessary

BSA (m$^2$) = $\sqrt{[{height(cm)}*{weight(kg)}]/3600}$

1in = 2.54cm

1kg = 2.2lbs

carboplatin dose = AUC*(GFR+25)

The target AUC is a variable specific to the type of cancer being treated and will be given on the exam, for instance there may be a target AUC of 5 for ovarian cancer or 6 or SCLC

GFR is often replaced with estimated CrCl

eCrCl = ((140-age)*weight)/(72*SCr*0.85/1 in women/men)

Reduction in the following when compared to BSA based dosing:
Thrombocytopenia (loss of platelets)
Neuropathy (Tingling, numbness, pain, etc in extremities)
Nephrotoxicity (kidneys)

Doses > or equal to 500mg/m$^2$

Therapeutic drug monitoring
Administration of leucovorin
hydration for optimal elmination
alkalization of urine to prevent risk of precipitation and renal injury

Methotrexate levels are measured every 24 hours after the start of a methotrexate infusion, and leucovorin is administered until methotrexate levels are <0.1 uM. The dose and frequency of leucovorin administration is determined by the concentration of MTX and the time after infusion on a graph that will be given.

ANC = ((%neutrophils + %bands)*WBC))/100

Completely free of disease

The disease has disappeared

The disease has shrunk

The disease is not growing or shrinking

The disease is growing