Professional Documents
Culture Documents
Anti-cancer
Chemotherapeutic
Agents
Dr. Jeff R. Wilcke
Therapeutic Principles
Diagnosis
&
Drug
Selection
I
N
P
U
T
Absorption
Distribution
Metabolism
Elimination
Pharmacokinetics
Toxicity
&/OR
Efficacy
Pharmacodynamics
Therapeutic Endpoints
Efficacy without toxicity
Tentative administration
You may affect bone marrow ONLY rather than bone marrow AND
tumor
Drug Resistance
Reduces tumor response, bone marrow still sensitive
OR
Nagahiro Saijo, Chemotherapy: the more the better? Overview, Cancer Chemother Pharmacol (1997) 40
(Suppl): S100 S106
These are the SAME PATIENTS. What separates them on the Graph labeled
A ?
Peak Concentration
AUC
Absorption
Oral
Absorption
Intramuscular
Activation
Hepatic
Intracellular phosphorylation
e.g fludarabine
e.g. doxorubicin
Distribution
Most target intra-cellular sites
Distribution
Active Metabolite distribution
Tumor vascularity
Tumor may outgrow blood supply
Interaction with angiogenesis inhibitors?
Elimination
Hepatic Metabolism
P450 metabolism
Hydrolysis
Renal elimination unchanged (what does
this mean for owner safety?)
Dosing Chemotherapeutics
What are we really doing in veterinary
patients?
Dosing Chemotherapeutics
Body surface area
mg/kg
Total dose
Dose to pharmacokinetic target
Dosing Chemotherapeutics
Traditional dosing on Body Surface Area
10 bw in grams
10,000
Cats
10.1 bw in grams
10,000
2/3
2/3
Meters Squared
30 mg/M2 Adriamycin
Dogs <10 kg received more than 1.5 mg/kg
Oral Chemotherapy
Widely used in Veterinary Chemotherapy
Oral Chemotherapy
Alkylating Agents
cyclophosphamide (Cytoxan)
Excellent absorption characteristics
Most widely used (therefore most experience)
Oncology, immunology uses
melphalon (Alkeran)
busolfan (Myleran)
procarbazine (Mutalane)
Oral Chemotherapy
Antimetabolites
capecitabine (Xeloda)
Oral pro-drug version of fluorouracil
Mercaptopurine (Purinethiol)
Variable and incomplete absorption
Oral Chemotherapy
Hormonal Oncologics
Tamoxifen
Mitosis Inhibitors
Others
Hydroxurea
Well aborbed
IM Chemotherapy
aspariginase (Elspar)
leuprolide (Lupron)
Intravenous Chemotherapy
Why?
Gemcitabine
Controlled intravenous infusion
Implantable polymers