Chemotherapy

From Dog

Chemotherapy is a large medical field involving the pharmaceutical therapy of cancer.

Individual chemotherapy regimens depend on a number of critical factors such as form of neoplasia, breed of dogs, evidence of metastasis and general health of the dog.

Kamofsky's performance criteria may be used as a rough guide to determine suitability of canine patients to chemotherapy[1].

Specific chemotherapeutic agents:

- Methylating alkylating agents - procarbazine, dacarbazine, temozolomide
- Nitrogen mustard alkylating agents - cyclophosphamide, chlorambucil, melphalan, mechlorethamine, ifosfamide
- Chloroethylating nitrosourea alkylating agents - lomustine (CCNU), carmustine (BCNU) , fotemustine
- Platinum-based alkylating agents - cisplatin, carboplatin


Commonly used agents


Agent Indications Dose rate Route Notes
Actinomycin-D lymphoma 0.5 - 0.8 mg/m2 every 1 - 3 weeks IV monitor CBC, may cause gastroenteritis
Asparaginase lymphoma 10, 000 units/m2 SQ, IM monitor CBC
Carboplatin osteosarcoma, other carcinomas <15 kg: 250 mg/m2, >15 kg: 300 mg/m2 given once every 3 - 4 weeks IV acute renal injury, pretreatment with diuretic 4 hrs prior and 2 hrs post
Chlorambucil low-grade lymphoma, lymphocytic leukemia 6 - 8 mg/m2 daily for 14 days then q 2nd day, or 15 mg/m2 for 4 days repeated every 3 weeks PO neutropenia, thrombocytopenia, monitor CBC/MBA fortnightly for first 2 months
Cisplatin osteosarcoma and other carcinomas <5 kg: 50 mg/m2, 5-20 kg: 60 mg/m2, >20 kg:70 mg/m2 IV, intralesional acute renal injury, pretreatment with diuretic 4 hrs prior and 2 hrs post
Cyclophosphamide lymphoma 200 - 250 mg/m2 PO, IV Monitor CBC
Doxorubicin lymphoma, osteosarcoma small dogs 1 mg/kg, large dogs 30mg/m2 given every 2 - 3 weeks IV monitor CBC, may caused gastroenteritis
Ifosfamide hemangiosarcoma, leiomyosarcoma 375 mg/m2 IV acute renal injury, pretreatment with diuretic 4 hrs prior and 2 hrs post
Lomustine lymphoma, mast cell tumors, glioma, meningioma 60 - 90 mg/m2 every 3 - 4 weeks PO leucopenia and thrombocytopenia common
Mechlorethamine MOPP protocol for lymphoma 3 mg/m2 IV caution with extravasation
Melphalan multiple myeloma 1.5 mg/m2 on alternate days or 10 days on, 10 days off PO monitor CBC
Mitoxantrone transitional cell carcinoma 5 - 6 mg/m2 every 3 weeks IV monitor CBC
Procarbazine MOPP protocol for lymphoma 50 mg/m2 daily for 14 days PO monitor CBC
Vinblastine lymphoma, mast cell tumors 2 mg/m2 every 7 - 14 days IV monitor CBC
Vincristine lymphoma, sarcomas, transmissible venereal tumor 0.5 - 0.75 mg/m2 IV monitor CBC


Types of chemotherapy regimens vary depending on the form of neoplasia:

  • Surgical debulking of single solid tumors if restricting vital organs
  • Multi-drug protocol - use of several chemotherapy drugs (prednisolone, L-asparaginase, vincristine, cyclophosphamide, doxorubicin, idarubicin[2] and epirubicin[3]). Weekly chemotherapy treatments are given for approximately 8 weeks. The treatments are then spaced to every 2 weeks to complete a total of 6 months of treatment. The average survival time for patients with stage IIIa or IVa lymphoma treated with this protocol is 1 and 1/2 years.
  • Madison Wisconsin lymphoma protocol
  • MOPP lymphoma protocol
  • University of Florida protocol - lomustine, vincristine, procarbazine and prednisolone[4]
  • University of California CHOP protocol - cyclophosphamide, doxorubicin, vincristine and prednisone. Average survival time 8 - 10 months[5].
  • Doxorubicin - a total of 5 treatments of doxorubicin at 3-week intervals. The average survival time with this approach is 10-11 months.
  • Prednisolone - often used as a palliative drug in non-compliant patients or financially challenged cases. Survival time limited to 2 - 3 months.
  • Total body irradiation and autologous transplantation[6]
  • Immunotherapy with multivalent immunogens[7]

Masitinib has also shown benefit as an adjuvant with doxorubicin treatment[8].

Actinomycin-D[9] and carmustine[10] are also effective for rescue chemotherapy of dogs with relapsed or resistant neoplasias.

Alternative drugs such as acemannan have also been trialed with variable responses[11].

Lansoprazole has also been used as a rescue protocol in dogs undergoing chemotherapy for lymphoma that have adverse side-effects associated with treatment.

References

  1. Spugnini EP et al (2011) Lansoprazole as a rescue agent in chemoresistant tumors: a phase I/II study in companion animals with spontaneously occurring tumors. J Transl Med 9:221
  2. Vail DM et al (2012) Phase I study to determine the maximal tolerated dose and dose-limiting toxicities of orally administered idarubicin in dogs with lymphoma. J Vet Intern Med 26(3):608-613
  3. Elliott JW et al (2012) Epirubicin as part of a mufti-agent chemotherapy protocol for canine lymphoma. Vet Comp Oncol Feb 28
  4. Fahey CE et al (2011) Evaluation of the University of Florida lomustine, vincristine, procarbazine, and prednisone chemotherapy protocol for the treatment of relapsed lymphoma in dogs: 33 cases (2003-2009). J Am Vet Med Assoc 239(2):209-215
  5. Rebhun RB et al (2011) CHOP chemotherapy for the treatment of canine multicentric T-cell lymphoma. Vet Comp Oncol 9(1):38-44
  6. Escobar C et al (2012) Hematologic changes after total body irradiation and autologous transplantation of hematopoietic peripheral blood progenitor cells in dogs with lymphoma. Vet Pathol 49(2):341-343
  7. Henson MS et al (2011) Immunotherapy with autologous tumour antigen-coated microbeads (large multivalent immunogen), IL-2 and GM-CSF in dogs with spontaneous B-cell lymphoma. Vet Comp Oncol 9(2):95-105
  8. Zandvliet M et al (2013) Masitinib reverses doxorubicin resistance in canine lymphoid cells by inhibiting the function of P-glycoprotein. J Vet Pharmacol Ther Jan 31
  9. Bannink EO et al (2008) Actinomycin D as rescue therapy in dogs with relapsed or resistant lymphoma: 49 cases (1999--2006). J Am Vet Med Assoc 233(3):446-451
  10. Ricci Lucas SR et al (2004) Carmustine, vincristine, and prednisone in the treatment of canine lymphosarcoma. J Am Anim Hosp Assoc 40(4):292-299
  11. Kruth SA (1998) Biological response modifiers: interferons, interleukins, recombinant products, liposomal products. Vet Clin North Am Small Anim Pract 28(2):269-295