Chemotherapy Protocols 1

Chemotherapy Protocols for Treatment of Neoplastic Diseases In Small

Animals
Victoria S. Larson, DVM, DACVO
Michael Henson, DVM
Maria Crowley
Editor’s Note: The following protocols are presently being used by the Veterinary Comparative Oncology
group at the University of Minnesota Veterinary Teaching Hospitals. Other protocols for
chemotherapeutic agents to treat neoplastic diseases may be found in numerous references. Because there
is considerable ongoing clinical research in veterinary oncology, the reader is urged to follow the current
literature, as therapeutic protocols for animals with neoplastic diseases will be continuously modified.

Canine Lymphoma Treatment Protocol “PACO”

Week 1
A. Prednisone 40 mg/m2 PO; continue once daily throughout 12 weeks
B. L-Asparaginase injection 10,000U/m2 SQ
Week 2
A. Vincristine injection 0.65 mg/m 2 IV
B. Cyclophosphamide tablets 50 mg/m 2 on days 3, 4, 5, and 6 of week 2
Week 3
A. Perform CBC; must have results before treating
B. Doxorubicin 30 mg/m2 IV
Week 4
A. Perform CBC; must have results before treating
B. Vincristine injection 0.65 mg/m 2 IV
Week 5
A. Vincristine injection 0.65 mg/m 2 IV
B. Cyclophosphamide tablets 50 mg/m 2 PO on days 3, 4, 5, and 6 of week 5
Week 6
A. Perform CBC; must have results before treating
B. Doxorubicin 30 mg/m2 IV
Week 7
A. Off; No chemotherapy
Week 8
A. Vincristine injection 0.65 mg/m 2 IV
B. Cyclophosphamide tablets 50 mg/m 2 PO on days 3, 4, 5, and 6 of week 8
Week 9
A. Perform CBC; must have results before treating
B. Doxorubicin 30 mg/m2 IV
Week 10
A. Perform CBC; must have results before treating
B. Vincristine injection 0.65 mg/m 2 IV
 Chemotherapy Protocols 2

Week 11
A. Vincristine injection 0.65 mg/m 2 IV
B. Cyclophosphamide tablets 50 mg/m 2 on days 3, 4, 5, and 6 of week 11
Week 12
A. Vincristine injection 0.65 mg/m2 IV
B. Chlorambucil 4 mg/m2 PO every other day
C. Prednisone 40 mg/m2 PO every other day
Maintenance
A. Vincristine injection 0.65 mg/m 2 IV every 3 weeks
B. Chlorambucil 4 mg/m2 PO every other day
C. Prednisone 40 mg/m2 PO every other day

Doxorubicin Protocol for Canine Lymphosarcoma

1. Induction Phase
A. Doxorubicin (Adriamycin®): 30 mg/M2 given intravenously once ever 14 days for 5 cycles.
2. Maintenance Phase
There is no maintenance therapy on this protocol. Animals completing the induction phase should be
evaluated every 2-3 months.
B. Special Precautions
1. Avoid extravasation of the drug. Use an indwelling catheter.
2. Reconstituted drug should be administered over a period of about 20 minutes into the side
port of a freely running intravenous infusion of 0.9% NaCl.
3. Allergic reactions to the drug during administration may occur. They may be reduced by
administering the drug over 20 minutes.
4. Doxorubicin can cause dose-dependent cardiotoxicity. Dogs should not receive more than
150 mg/M2 cumulative total dose. Preexisting cardiac disease should be ruled out with a
ECG and echocardiogram. Generally, dogs with severe arrhythmias or a decreased ventricular
shortening fraction should not receive doxorubicin.
5. Anorexia, vomiting and/or diarrhea may be observed 2-5 days post therapy. Clinical signs vary
from mild to severe.
6. Doxorubicin may cause severe neutropenia. A CBC should be evaluated 7 days following the
first doxorubicin injection and prior to subsequent injections. If neutrophil count decreased to
<1000/µl, the drug should not be administered and the dose reduced 10% at the next
administration if the animal has no physical signs. If physical signs are present in conjunction
with a low white count, the dose is reduced 25%.
7. Special precautions for handling doxorubicin:
a. Doxorubicin should be reconstituted in a biologic safety hood, if possible.
b. Skin contact with the drug should be avoided.
c. Care should be taken to avoid inhalation of the powder.
d. Double gloves should be worn when handling the drug.
e. Pregnant females should avoid handling or administering the drug.
 Chemotherapy Protocols 3

COP (Cyclophosphamide, vincristine, prednisone) Protocol

This protocol is administered on a 3 week (21 day) cycle for one year. It involves the use of vincristine,
cyclophosphamide and prednisone. median remission time is about 7-9 months.
Week 1 (Day 1)
A. Start prednisone at 1 mg/kg PO daily (continue throughout treatment)
B. Vincristine at 0.75 mg/m2 IV
C. Cyclophosphamide at 200 - 250 mg/m2 PO divided over 2-5 days.
Week 2 (Day 10)
A. Vincristine injection 0.75 mg/m 2 IV
Week 3 (Day 21)
A. Vincristine injection 0.75 mg/m 2 IV
Week 4 (Day 28)
A. Vincristine injection 0.75 mg/m 2 IV
B. Cyclophosphamide at 200 - 250 mg/m2 PO divided over 2-5 days.
Week 7 (Day 49)
A. Continue vincristine and cyclophosphamide as on week 4, decrease prednisone to every 48
hours

Continue this cycle for one year. begin to wean patient off prednisone after 12 months.

Canine Lymphosarcoma Reinduction of Remission Protocol

INDICATIONS: For use in patients that have come out of remission on other protocols.
1. DRUGS:
A. L-Asparaginase: 10,000 units/m2 SQ on week one. Note: Drug may be unavailable
B. Doxorubicin: 30 mg/M2 intravenously on days 8, 22, 36, & 50
CBC’s: 7 days post doxorubicin

Canine Sarcoma and Carcinoma Treatment Protocol “AC”

I. INDICATIONS
This protocol is indicated for the treatment of thyroid and mammary carcinomas in the dog, either as
primary therapy for non-resectable tumors or as adjuvant therapy following surgery.
II. DRUGS
A. Doxorubicin (Adriamycin®): 30 mg/M2 IV on day 1
B. Cyclophosphamide (Cytoxan®): 50 mg/M2 PO on days 3-6
C. Repeat every 21 days for a total of 3 cycles.
III. TOXICITIES
Doxorubicin may be associated with a variety of toxicities in the dog. Acute toxicities include
anaphylaxis and cardiac arrhythmias. Short-term toxicities may include gastrointestinal toxicity and
myelosuppression. The principal chronic toxicity is a cumulative, dose dependent, cardiac toxicity
leading to myocardial degeneration and irreversible congestive heart failure. Total doxorubicin dose
 Chemotherapy Protocols 4

should not exceed 250 mg/M2. A CBC, including a platelet count should be monitored 10 days
following initial therapy and subsequently prior to each new cycle. If the neutrophil count falls
below 1,000/µl or platelet counts fall below 50,000/µl, treatment should be suspended until these
counts return to normal.
IV. ANAPHYLAXIS PREVENTION
Give doxorubicin over 20 minutes.
V. MISCELLANEOUS
A. If Cytoxan ® tablets should not be split. Round down dosage to the nearest dose to give
complete tablets.
B. Doxorubicin and its metabolites are excreted in the urine. Clients who are pregnant should not
come in contact with urine from treated animals for at least 72 hours following therapy.
C. Doxorubicin should be reconstituted under a laminar-flow hood. Delivery of the drug should
be done with extreme care, including double-gloving of the administrator and holder.

Canine Osteogenic Sarcoma Adjuvant Protocol

INDICATIONS: use following limb amputation in dogs with osteogenic sarcoma
Day 1: Doxorubicin 30 mg/m2 IV over 20 minutes via catheter and fluids (see above)
Day 7: Perform CBC
Day 22 (3 weeks from initial doxorubicin dose): Carboplatin 300 mg/m2. Place IV catheter and
give via slow push without extra fluids
Day 44 (3 weeks from initial carboplatin dose): Recheck CBC; if WBC is > 4000 (neutrophils
>3500) and platelets > 60,000 (and the CBC values drawn on day 7 were above these
parameters) give additional doxorubicin dose of 30 mg/m2 (as above)
Repeat as above every 3 weeks alternating doxorubicin and carboplatin until a total of 3 doses of
each have been given.

Canine Multiple Myeloma Chemotherapy Protocol

I. DRUGS
A. Melphalan: 0.l mg/kg PO daily for 10 days; then 0.05 mg/kg daily, continuously
B. Prednisone: 0.5 mg/kg PO daily for 10 days; then 0.5 mg/kg on alternate days, continuously.
II. ADMINISTRATION AND USES
A. Melphalan is an alkylating agent which tends to be less toxic than cyclophosphamide.
However, bone marrow suppression may occur. Monthly re-checks (w/CBC) are advisable
during chronic therapy with melphalan. Long term administration commonly results in
thrombocytopenia.
B. Myeloma patients are extremely susceptible to infection. Care should be taken with invasive
procedures. On-going infections should be treated following results of culture and sensitivity
testing.
C. Cyclophosphamide may be substituted for melphalan when resistance develops, but beware
of hemorrhagic cystitis secondary to cyclophosphamide and discontinue at first sign.
D. Careful staging work-up is important and should include: serum and urine electrophoresis and
a bone marrow biopsy and aspirate.
 Chemotherapy Protocols 5

Treatment Protocols For Canine Mast Cell Tumors

VCP Protocol
This protocol is administered on a 3 week (21 day) cycle. It involves the use of vinblastine,
cyclophosphamide and prednisone.
Week 1
A. Prednisone 1 mg/kg PO; continue throughout treatment
B. Vinblastine 2 mg/m2 IV
Week 2
A. Perform CBC; must have results before treating if WBC >4500 (>3000 neutrophils and 60,000
platelets), give cyclophosphamide at 200 - 250 mg/m2 PO over 2-4 days.
B. Vincristine injection 0.65 mg/m 2 IV
Week 3
A. Vinblastine 2 mg/m2 IV
Continue this cycle for 6-8 months. begin to wean off the prednisone.

CCNU Protocol
First occurrence of a single tumor w/o metastasis and well differentiated: (Grade I)
1. Wide Surgical Excision (No follow-up therapy if surgical margins are clean)
First occurrence of a single tumor w/o metastasis and intermediate or poorly differentiated
1. Wide Surgical Excision*
2. Radiation Therapy Following Excision--Probably Best Alternative (94% disease free interval at 1
year, n=342 in recent AMC study)
3. Prednisone and Lomustine Therapy Following Excision--Alternative Therapy
Single Tumor with LN Metastasis: Any Histologic Stage
1. Wide Surgical Excision of Tumor and Lymph Node
2. Radiation Therapy to Excision Site(s)--Best Alternative
3. Prednisone and Lomustine Following Excision (in addition to radiation or alone if radiation is not
selected)
Prednisone Dose: 40-50 mg/M2 PO for a week, then 20-25 mg/M2 PO every other day
Lomustine (CCNU) Dose: 90 mg/M2 PO every 4 weeks for 6 months (Note: Neutropenia at 7 days
post tx and thrombocytopenia at 21 days post tx and with long term administration; consider giving
prophylactic antibiotics such as trimethoprim/sulfa at 5-15 mg/kg PO twice daily for 10 days after
giving lomustine).

* Local injection of a glucocorticoid is an alternative to surgery and radiation therapy although

ability to achieve local control is significantly reduced. Triamcinolone acetonide, 1 mg intralesionally
per cm of tumor every 2-3 weeks can be used.

Feline Lymphoma Treatment Protocol “COPA”

Week 1
A. Prednisone 40 mg/m2 PO; continue once daily to week 7s
B. Vincristine injection 0.65 mg/m 2 IV
C. Cyclophosphamide tablets 300 mg/m2 PO (given at clinic)
 Chemotherapy Protocols 6

Week 2
A. Perform CBC; must have results before treating
B. Vincristine injection 0.65 mg/m 2 IV
Week 3
A. Vincristine injection 0.65 mg/m 2 IV
Week 4
A. Vincristine injection 0.65 mg/m 2 IV
B. Cyclophosphamide tablets 300 mg/m2 PO
Week 5
A. Perform CBC and serum creatinine
Week 7
A. Doxorubicin 25 mg/m2 IV
B. Begin taper of prednisone dosage
Week 8
A. Perform CBC and serum creatinine
Week 10
A. Doxorubicin 25 mg/m2 IV
Week 11
A. Perform CBC and serum creatinine
Week 13
A. Doxorubicin 25 mg/m2 IV
Week 16
A. Doxorubicin 25 mg/m2 IV
Week 19
A. Doxorubicin 25 mg/m2 IV
Week 20
A. Perform CBC and serum creatinine
Week 22
A. Doxorubicin 25 mg/m2 IV
Week 25
A. Doxorubicin 25 mg/m2 IV
Week 26
A. Perform CBC and serum creatinine
Chemotherapy agents should be administered on the same day of each week; if not possible, give the
following day. After 26 week protocol completed, once monthly rechecks are recommended to ensure that
cat is maintaining remission.