Systemic Chemotherapy for Oncologic Diseases

CHAPTER 4 Systemic Chemotherapy for Oncologic Diseases



Teresa A. Burns, C. Guillermo Couto


Neoplastic diseases are commonly encountered in general equine practice; until recently, most tumors were managed with surgery or palliative care, but at present many therapeutic options are available to the equine practitioner. Cutaneous neoplasms, particularly squamous cell carcinomas and the various forms of sarcoids, are the most common tumors in horses; several therapeutic protocols for these tumor types have been published on the basis of results of randomized, controlled clinical trials. Topical and intralesional application of antineoplastic drugs are the primary modes of treatment currently used for these conditions (see Chapters 151, Skin Tumors, and 152, Equine Sarcoid: What’s New in Diagnosis and Treatment).


Hematologic malignancies, particularly lymphomas, occur in the horse, albeit at a lower frequency than in other domestic species. In contrast to other companion animal species, primarily dogs and cats, affected horses historically have been given a grave prognosis and were often subjected to humane euthanasia immediately on diagnosis. Although the long-term prognosis for affected horses remains unclear, systemic chemotherapy has been administered to many horses with lymphoma at our institution and has achieved acceptable to good palliation of disease. Although the efficacy of the protocols we have used has not been evaluated with rigorous controlled clinical trials, horses receiving systemic chemotherapy appear to tolerate the drugs very well and often experience partial or complete remission or acceptable palliation of their disease. This chapter focuses on the use of systemic chemotherapy in the treatment of hematologic neoplasms in the horse as well as some practical guidelines for handling and disposal of these drugs for the equine practitioner.



THEORETICAL CONCEPTS


Goals of chemotherapy for any neoplastic disease include maximizing tumor cell kill while minimizing toxicity to the patient and drug exposure to health care personnel and, in veterinary medicine, the owners and handlers of the patient. Antineoplastic chemotherapy protocols in domestic animals tend to be less aggressive, using lower doses and longer treatment intervals than their human counterparts, because prolonged survival with an acceptable to good quality of life, rather than potential cure, is the ideal outcome of treatment in most situations, particularly in animals with hematologic malignancies. In equine oncologic practice, palliating the disease until some previously set time point, for example foaling, appears to be a reasonable goal, particularly regarding lymphoma. Moreover, in companion horses, the treatment goal is similar to that in small animals with cancer: to provide the longest remission possible with the best quality of life.


Multiple-drug protocols are advocated in the treatment of hematologic malignancies to minimize acquired drug resistance of tumor cells. For example, it has been hypothesized that mutations leading to drug resistance occur at a rate of 1 in 105 cells per gene in question. If 1 g of tumor tissue contains 109 cells, that tumor should be expected to contain 104 cells resistant to a given drug or class of drugs. However, resistance to two drugs should be expected to occur in less than 1 in 1010 cells, that is, less than 1 cell per 1 g tumor. This forms the rationale behind multidrug therapy, in which, ideally, drugs with different mechanisms of action and non-overlapping toxicities are used.



PROTOCOLS


At our institution, most chemotherapy protocols for horses with lymphoma begin with an induction protocol consisting of three drugs: an alkylating agent, an antimetabolite, and a corticosteroid. The alkylating agent and the antimetabolite are given on an alternating basis at 1- to 2-week intervals, and the corticosteroid is given daily or every other day. A typical cytosine, arabinoside, prednisolone (CAP) protocol for induction of remission in horses with lymphoma includes cyclophosphamide (1 g per treatment for a 450-kg horse, administered intravenously through a catheter) and cytosine arabinoside (1.0 to 1.5 g per treatment, administered intramuscularly or subcutaneously) given on an alternating basis every 2 weeks with prednisolone (1 mg/kg, orally) given daily (i.e., cyclophosphamide on week 1, cytosine arabinoside on week 3, cyclophosphamide on week 5, and so forth). If the horse is larger or smaller than 450 kg, drug dosages can be calculated on a mg/m2 or international unit/m2 basis, with body surface area calculated according to the following formula:



image



Physical examination and hematologic evaluation (complete blood count [CBC]) are performed before each treatment, and treatment is delayed if neutropenia or evidence of sepsis (fever or other clinical signs, identified focus of infection) is present. In our experience, these are uncommon complications of cytotoxic chemotherapy in horses. Thus far, in more than 20 years of administering chemotherapy to horses, we have documented only one episode of neutropenia associated with carboplatin and fluorouracil administration.

Related posts:

  1. Adverse Drug Reactions
  2. Equine Viral Arteritis
  3. Coagulopathies
  4. Nutritional Factors in Developmental Orthopedic Disease

Stay updated, free articles. Join our Telegram channel
Tags:
May 28, 2016 | Posted by in EQUINE MEDICINE | Comments Off on Systemic Chemotherapy for Oncologic Diseases

Full access? Get Clinical Tree
Get Clinical Tree app for offline access