Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

CHAPTER 15 CANCER CHEMOTHERAPY
basophilic leukemia in veterinary patients have been
treated with hydroxycarbamide, with varying success.
Mechanism of action
Hydroxycarbamide (hydroxyurea) is a synthetic cell
cycle-specific drug with its effect in the S phase. It inhibits
ribonucleotide reductase activity, the rate-limiting
catalytic enzyme in the de novo synthesis of deoxyribonucleotide
triphosphates in DNA synthesis and repair.
Mechanism of drug resistance
Tumor cells achieve resistance to hydroxycarbamide
(hydroxyurea) by increasing cellular ribonucleotide
reductase activity.
Formulations and dose rates
Hydroxycarbamide is only available in capsules, which are too large
for most veterinary patients. The capsules should be reformulated to
ensure accurate dosing and prevent inadvertent overdosage.
DOGS AND CATS
• Because hydroxycarbamide (hydroxyurea) has an excellent oral
absorption, it is typically given PO
• The dose should be adjusted to achieve the desired clinical
effect, but a starting dose of 30 mg/kg for 7 d reduced to
15 mg/kg is the recommended starting point
Pharmacokinetics
Pharmacokinetic data are lacking in the dog and cat.
In humans, the elimination half-life is 3.5–4.5 h.
Pharmacokinetic studies are best described by a onecompartment
model with parallel Michaelis–Menten
metabolism and first-order renal excretion. A formula
for dose adjustment with renal insufficiency has not
been developed. Hydroxycarbamide (hydroxyurea)
readily enters the CSF. Pathways for metabolism are
undefined.
Adverse effects
● The dose-limiting toxicity is myelosuppression but it
is uncommon with recommended doses.
● Macrocytic red blood cells have been reported in
humans receiving chronic hydroxycarbamide (hydroxyurea)
therapy and one of the authors has seen this
in canine and feline patients.
● Paronychia is reported in cats receiving hydroxycarbamide
but does not preclude its successful use in
this species.
● Hydroxycarbamide is associated with an increased
risk of developing leukemia in human patients but
veterinary patients do not typically receive therapy
for long enough to induce this problem.
Known drug interactions
No clinically significant drug interactions have been
identified.
FURTHER READING
Allwood M, Stanley A, Wright P (eds) 2002 The cytotoxics handbook,
4th edn. Radcliffe Medical Press, Oxford
Bishop Y (ed.) 2005 Veterinary formulary, 6th edn. Pharmaceutical
Press, London
Chabner B, Longo DL (eds) 1996 Cancer chemotherapy and biotherapy:
principles and practice, 2nd edn. Lippincott-Raven, New York
Foye WO (ed.) 1995 Cancer chemotherapeutic agents. American
Chemical Society, Washington, DC
Kitchell B, LaRue SM, Rooks RL 2000 Veterinary cancer therapy
handbook: chemotherapy, radiation therapy and surgical oncology
for the practicing veterinarian, 2nd edn. AAHA Press, Lakewood, CO
Lana SE 2003 Chemotherapy. In: Dobson J, Lascelles D (eds) BSAVA
manual of canine and feline oncology, 2nd edn. BSAVA Publications,
Quedgeley, Glos
Morris J, Dobson J 2001 Small animal oncology. Blackwell Science,
Oxford
Morrison WB (ed.) 2002 Cancer in dogs and cats: medical and surgical
management. Teton New Media, Jackson, WY
Ogilvie GK, Moore AS 1995 Managing the veterinary cancer patient. a
practice manual. Veterinary Learning Systems, Trenton, NJ
Plumb DC 2005 Veterinary drug handbook, 5th edn. Blackwell, Oxford
Rosenthal RC, Michalski D 1991 Storage of expensive anticancer drugs.
JAVMA 198: 144-146
Steel RT, Lachant NA 1995 Handbook of cancer chemotherapy, 4th
edn. Little, Brown, London
Tennant B 2005 BSAVA small animal formulary, 5th edn. BSAVA
Publications, Quedgeley, Glos
Vail DM 2004 Veterinary Co-Operative Oncology Group – common
terminology criteria for adverse events (VCOG-CTCAE) following
chemotherapy or biological antineoplastic therapy in dogs and cats
v1.0. Vet Comp Oncol 2: 194-213
Withrow SJ, MacEwen G (eds) Clinical veterinary oncology, 3rd edn.
WB Saunders, Philadelphia, PA
Safety/UK legislation
COSHH 2002 Control of Substances Hazardous to Health Regulations
2002. Approved Code of Practice and Guidance, 4th edn. HSE
Books, London
HSE Information Sheet MISC615 2003 Safe handling of cytotoxic drugs.
HSE, London
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