Chemotherapy, General and Specific Drugs
World Small Animal Veterinary Association World Congress Proceedings, 2015
T. Kobayashi, DVM, DACVIM (Oncology)
Japan Small Animal Cancer Center, Tokorozawa, Japan

General Information

1.  Dose intensity: The aim of chemotherapy is to administer the maximum possible doses at the shortest possible dosing interval (dose intensity). Any decrease in the administered dose can result in a significant reduction in drug efficacy. Giving optimal doses is very important.

2.  Remission status: The clinical measurements of the tumor response to cancer chemotherapy are useful for predicting the impact of treatment on the extent of disease or time interval of tumor control. Conventional measures of treatment response include:

 Complete remission (CR) is the complete disappearance of the tumor and symptoms of disease.

 Partial remission/response (PR) is a ≥ 50% of decrease in tumor volume or decrease of > 30% in tumor maximum diameter.

 Stable disease (SD) is neither an increase nor a decrease in tumor size or disease symptoms.

 Progressive disease (PD) is a > 25% increase in tumor volume, > 20% increase of tumor maximum diameter, or appearance of new lesions.

3.  Side effects: The most clinically important toxicoses include bone marrow suppression, alopecia, and gastrointestinal (BAG adverse effects), perivascular slough (extravasation), cystitis, hypersensitivity and cardiac toxicity. Specific side effects for each drug will be discussed below.

Specific Drugs

1.  Carboplatin (CBDCA)

 Class: Platinum compounds

 Indication: Carcinoma and melanoma in dogs and cats, canine osteosarcoma, feline vaccine-site sarcoma

 Routes: Intravenous, intralesional, intracavitary

 Duration: 5–10 minutes slow push or 30 minutes infusion

 Dosage: Small dog breeds: 200–250 mg/m2 q 3 wk; middle dog breeds: 250–300 mg/m2 q 3 wk; large dog breeds: 300–350 mg/m2 q 3 wk; cats: 200–225 mg/m2 q 3 wk

 Toxicities: Mainly myelosuppression (neutrophil nadir at day 14)

 Metabolism/excretion: Predominantly excreted in the urine

 Precautions: Use with caution in dogs and cats with reduced kidney function; must be diluted with 5% dextrose in water; CBC is required every week

 Cost: $$$

2.  Cisplatin (CDDP)

 Class: Platinum compounds

 Indication: Various carcinoma, canine osteosarcoma, mesothelioma (intracavitary)

 Routes: Intravenous, intralesional, intracavitary

 Duration: 20 minutes infusion; must be given along with high rate of intravenous saline diuresis before and after administration

 Dosage: Dogs only; 50–70 mg/m2 q 3 wk

 Toxicities: Myelosuppression (neutrophil nadir at day 5 and day 16), vomiting, nephrotoxicity, neurotoxicity including ototoxicity

 Metabolism/excretion: Predominantly excreted in the urine

 Precautions: Use with caution in dogs with reduced kidney function; smaller dogs may be at increased risk for toxicity; fatal to cats!

 Cost: $$

3.  Cyclophosphamide (CPA)

 Class: Alkylating agents

 Indication: Lymphoma and lymphocytic leukemia in dogs and cats; metronomic chemotherapy

 Routes: Intravenous, per os (PO)

 Duration: Bolus administration

 Dosage: Dogs: 250 mg/m2 intravenous or 50 mg/m2 PO 4 days/week as a part of lymphoma protocol, or 15 mg/m2 PO q 24 h as a metronomic therapy; cats: 10 mg/kg intravenous as a part of lymphoma protocol

 Toxicities: Myelosuppression (neutrophil nadir at day 7–10); anorexia and vomiting may begin 6 hours after administration intravenously, sterile hemorrhagic cystitis

 Metabolism/excretion: Require in vivo activation. Cyclophosphamide and its metabolites are excreted by the kidney.

 Precautions: Teratogenic and do not crush cyclophosphamide tablets

 Cost: $

4.  Vincristine (VCR)

 Class: Plant alkaloids

 Indication: Lymphoma and lymphocytic leukemia in dogs and cats, transmissible venereal tumor

 Routes: Intravenous only

 Duration: Bolus administration

 Dosage: Dogs: 0.5–0.7 mg/m2 weekly; cats: 0.025 mg/kg - 0.5 mg/m2 weekly

 Toxicities: Myelosuppression; anorexia, vomiting, paralytic ileus mainly in cats, peripheral neuropathy, moderate perivascular slough when extravasated

 Metabolism/excretion: Rapidly cleared from plasma and excreted in bile

 Precautions: Moderate tissue damage can occur if given outside of a vein; decrease dose by 50% in animals with total bilirubin levels above 1.5 mg/dL

 Cost: $$

5.  Vinblastine (VBL)

 Class: Plant alkaloids

 Indication: Mast cell tumor in dogs and cats, lymphoma as a substitute of vincristine when severe ileus occurs in cats

 Routes: Intravenous only

 Duration: 5–10 minutes bolus

 Dosage: Dogs: 2–3 mg/m2 weekly; cats: 1.5 mg/m2 weekly in cats

 Toxicities: Myelosuppression (VBL > VCR); anorexia, vomiting, peripheral neuropathy (VCR > VBL), moderate perivascular slough when extravasated

 Metabolism/excretion: Rapidly cleared from plasma and excreted in bile

 Precautions: Moderate tissue damage can occur if given outside of a vein; decrease dose by 50% in animals with total bilirubin levels above 1.5 mg/dL

 Cost: $$

6.  Doxorubicin (DXR)

 Class: Antibiotics

 Indication: Lymphoma and lymphocytic leukemia in dogs and cats, various carcinomas, and sarcomas including osteosarcoma and hemangiosarcoma

 Routes: Intravenous only

 Duration: 30–60 minutes IV infusion. Diluted with saline before administration

 Dosage: Dogs: < 5 kg: 1 mg/kg q 3 wk; 5–10 kg: 25 mg/m2 q 3 wk; 10–15 kg: 25–30 mg/m2 q 3 wk: 15 kg <: 30 mg/m2 q 3 wk. Prophylactic antiemesis such as maropitant recommended on day 1–5 after administration; Cats: 20–25 mg/m2 q 3 wk

 Toxicities: Myelosuppression (neutrophil nadir at day 7–10); vomiting, diarrhea (sometimes hemorrhagic colitis), cardiac toxicity, hypersensitivity, alopecia, severe perivascular slough when extravasated, renal toxicity in cats

 Metabolism/excretion: Metabolized predominantly by the liver. Approximately 50% of the drug is excreted in bile

 Precautions: Can cause severe tissue damage if administered outside of the vein; damage to the heart can occur in dogs if a total cumulative dose is more than 180 mg/m2; decrease dose by 50% in animals with total bilirubin levels above 1.5 mg/dL

 Cost: $–$$

7.  L-asparaginase (L-ASP)

 Class: Enzymes

 Indication: Lymphoma and lymphocytic leukemia in dogs and cats

 Routes: Subcutaneous or intramuscular. Do not give intravenously

 Duration: Bolus administration

 Dosage: Dogs and cats: 400 U/kg or 10,000 U/m2

 Toxicities: Hypersensitivity reactions, pancreatitis, coagulopathy

 Metabolism/excretion: Not completely understood

 Precautions: Hypersensitivity reaction usually occurs within 60 minutes. Patients should be monitored in the clinic at least for 60 minutes after injection; pretreatment with antihistamines and steroid are recommended

 Cost: $–$$

    

References

1.  Gustafson D, Page RL. Cancer chemotherapy. In: Withrow SJ, Vail DM, Page RL, eds. Withrow & MacEwen's Small Animal Clinical Oncology. 5th ed. St. Louis, MO: Elsevier Saunders; 2014.

2.  Principles of cancer chemotherapy. In: Foale R, Demetriou J, eds. Small Animal Oncology. St. Louis, MO: Elsevier Saunders; 2010.

3.  Chemotherapy: properties, uses, and patient management. In: Ogilvie GK, Moore AS, eds. Managing the Canine Cancer Patient. Columbus, OH: Veterinary Learning Systems; 2006.

4.  Management of chemotherapy side effects. In: Crump K, Thamm DH, eds. Cancer Chemotherapy. Chichester, West Sussex, UK: John Wiley & Sons Ltd; 2011.

  

Speaker Information
(click the speaker's name to view other papers and abstracts submitted by this speaker)

Tetsuya Kobayashi, DVM, DACVIM (Oncology)
Japan Small Animal Cancer Center
Tokorozawa, Japan


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