Introduction

• Systemic chemotherapy for lymphoma Lymphosarcoma: overview is rarely attempted in horses because of the costs and issues around practicality in this species.
• In a multicenter study spanning 26 years, only 15 cases of chemotherapy administration for lymphoma were identified.
• The success rates for chemotherapy were reasonable, with a response rate of 93.3%. It is important to look at the breakdown of these data: only 33.3% of cases achieved complete remission, of which 3 out of the 5 cases had cutaneous lymphoma, which has a better prognosis in spite of treatment than other forms.
• Overall median survival time was 8 months.
• As with small animal chemotherapy protocols, the dose should be calculated according to the body surface area. The formula to calculate the body surface area of a horse is body surface area = weight (g^2/3) x 10.5/10⁴. The average body surface area for a typical horse is 5m².
• The following chemotherapy drugs for the treatment of lymphoma Lymphosarcoma: overview have been described in horses:
  • Doxorubicin Doxorubicin at 35-70 mg/m² IV.
  • Vincristine at 0.55-0.7 mg/m² IV.
  • L-asparaginase at 10,000 U/m² SQ.
  • Lomustine (CCNU) at 65 mg/m² IG.
  • Cyclophosphamide at 150-800 mg/m² IV.
  • Cytosine arabinoside at 175-250 mg/m² IV.

• Very little information is available on specific chemotherapeutic protocols in horses, but combinations of drugs that have been described for the treatment of lymphoma Lymphosarcoma: overview (with and without the inclusion of corticosteroids) include:
  • Doxorubicin Doxorubicin, vincristine, L-asparaginase, lomustine and cyclophosphamide.
  • Doxorubicin, vincristine, L-asparaginase, cyclophosphamide and cytosine arabinoside.
  • Doxorubicin, vincristine, L-asparaginase and cyclophosphamide.
  • Vincristine, L-asparaginase, cyclophosphamide and lomustine.
  • Vincristine, cyclophosphamide and cytosine arabinoside.
  • Doxorubicin, vincristine and cyclophosphamide.
  • Doxorubicin and lomustine.
  • Vincristine and cyclophosphamide.
  • Lomustine.

Important considerations

• In a series of 15 equids receiving chemotherapy for lymphoma, 9 had adverse effects that were attributable to the chemotherapy protocols.
• One horse died suddenly, 18 h after administration of doxorubicin Doxorubicin.
• Reported adverse effects include alopecia Hair: alopecia areata, neutropenia, lymphopenia, lethargy, neurotoxicity, gastrointestinal effects (colic Abdomen: pain - adult), and hypersensitivity.
• Hypersensitivity was associated with doxorubicin administration.
• Four of 7 horses receiving doxorubicin experienced adverse effects attributable to the drug despite premedication with flunixin meglumine Flunixin meglumine and diphenhydramine hydrochloride Diphenhydramine.
• Myelosuppression and gastrointestinal toxicity (eg inappetence, colic, and/or diarrhea) are possible toxicities of vincristine, cyclophosphamide and doxorubicin.
• Additional toxicities of vincristine include:
  • Severe tissue necrosis and extravasation injury if given outside of the vein.
  • Peripheral neuropathies, most commonly manifested as paralytic ileus Gastrointestinal: ileus.
• An additional toxicity of cyclophosphamide includes sterile hemorrhagic cystitis in other species. It is not known if this may also occur in the horse.
• Additional toxicities of doxorubicin include:
  • Severe tissue necrosis and extravasation injury if given outside of the vein. Doxorubicin Doxorubicin should be administered through a "clean stick" catheter. Careful monitoring of the patient is advised during administration to ensure the catheter remains in place.
  • Hemorrhagic colitis Colon: colitis.
  • Anaphylactoid reactions Anaphylaxis secondary to mast cell degranulation.
  • Acute cardiac toxicity manifested as arrhythmias Heart: sinus arrhythmia, and cumulative toxicity may also occur.
• A complete blood count (CBC) Blood: overview with platelet count must be performed within 48 h prior to chemotherapy administration.
• Reduce chemotherapy dose by 20% in patients experiencing significant myelosuppression, GI toxicity and/or those requiring treatment delays during weekly administration.
• Extravasation Chemotherapy: extravasation injury is an important toxicity. Doxorubicin should be administered through a "clean stick" catheter and given over 30 minutes. Careful monitoring of the patient is advised during administration to ensure catheter remains in place. 
• Doxorubicin is toxic to cardiac myocytes. To avoid cumulative cardiotoxicity, maintain clear records of the total doxorubicin dose to date (in total mg, as well as total mg/m²) for each patient. No cardiotoxicity has been reported in (low numbers of) horses, but this is still a risk.

• Perform a CBC Blood: overview with platelet count Blood: platelet evaluation prior to every dose of chemotherapy. Delay chemotherapy by 3-7 days and recheck CBC if neutrophils <2000 cells/uL or if platelets <75,000 cells/uL. 
• Perform a CBC with platelet count 7 days after the first dose of doxorubicin to assess degree of myelosuppression (nadir). Consider prophylactic antibiotics in afebrile, apparently healthy patients with neutrophil counts <1000 cells/uL Blood: neutrophils. Consider hospitalization and treatment for sepsis (IV fluids Fluid therapy: overview and broad-spectrum antibiotics Therapeutics: antimicrobials) in febrile and/or sick patients with neutropenias. Once the nadir has been established, post-chemotherapy CBCs are unnecessary unless the patient becomes ill and/or if dose reductions are required (see below). 
• Reduce doxorubicin Doxorubicin dose by 20% in patients experiencing significant myelosuppression, GI toxicity and those requiring hospitalization due to toxicity. Following dose reduction, recheck CBC with platelet count 7 days after treatment. 

Legal and safety precautions

Further Reading

Publications

Refereed Papers

• Recent references from PubMed and VetMedResource.
• Luethy D, Frimberger A E, Bedenice D et al (2019) Retrospective evaluation of clinical outcome after chemotherapy for lymphoma in 15 equids (1991-2017). J Vet Intern Med 33 (2), 953-960 PubMed.