Chemotherapy: managing side effects and safe handling.

Chemotherapy is a common treatment modality in many veterinary cancer patients in addition to surgery and radiation therapy. Cytotoxic drugs can lead to complete remissions for some disseminated cancers (lymphoma, for example), be effective in decreasing tumor size, and may prolong life in many other types of metastatic cancers, such as osteosarcoma. The choice of specific therapies depends on tumor type (what it is), histologic grade of the tumor (how aggressive it is), stage of disease (where it is), and the patient’s (but mainly the pet owner’s) tolerance for the side effects of the various treatments. Most of the chemotherapy protocols designed for veterinary patients have a < 5% incidence of severe, life-threatening complications (1). Most veterinary chemotherapy patients enjoy a good quality of life while on therapy. This article will discuss some of the side effects associated with chemotherapy in veterinary patients and how to effectively treat them. In addition, an overview of chemotherapy safety for both patient and veterinary staff will be discussed. Veterinarians engaging in the practice of oncology require a thorough knowledge of the effects and toxicities of anticancer drugs. Since these agents possess the lowest therapeutic indices of any class of drugs, they produce frequent and predictable multi-system toxicities. Anticipation of possible complications and close attention to subtle clinical signs are essential to assure early introduction of prophylactic or therapeutic supportive care. Toxicities are most often acute, but chronic or delayed effects do occur. An index of suspicion for these problems is essential for their diagnosis. The Veterinary Cooperative Oncology Group (VCOG) has published a document outlining the common terminology criteria and providing a grading scale for adverse events following chemotherapy (2). Simply put, chemotherapy kills rapidly dividing cells. Unfortunately chemotherapy drugs do not differentiate between killing tumor cells and normal cells. Thus, the general side effects of chemotherapy include bone marrow suppression, gastrointestinal problems (nausea, vomiting, diarrhea), and alopecia (1). However, in addition to the general side effects seen, specific side effects can result from certain drugs, for example, doxorubicin (cardiotoxicity) and cisplatin (fatal pulmonary edema in cats, renal toxicity in dogs). The most common toxicity associated with chemotherapy is bone marrow suppression. Bone marrow cells divide rapidly because there is normally a high growth fraction in this tissue. Since activity of most anticancer drugs is greatest in tissues with a high growth fraction, the bone marrow is a prime target. The clinical result of myelosuppression is varying degrees of peripheral blood cytopenias. The rate of disappearance of individual blood cell lines correlates with the life span of that line. For example: RBC — 120 d (dogs), 70 d (cats); platelets — 5 to 10 d; granulocytes — 4 to 8 h. Granulocytopenia (specifically neutropenia) usually occurs first and is most often followed by thrombocytopenia. Anemia is rare and usually only mild to moderate. Neutropenia is usually the most serious and dose limiting cytopenia associated with chemotherapeutic drug administration. The nadir (time of the lowest neutrophil count) varies with individual drugs. Nadirs in small animals occur between 5 to 10 d — standard practice is to run a complete blood (cell) count (CBC) at 7 d post-chemotherapy administration in order to detect the nadir, though the nadir can be missed. It is important to note that some drugs have a delayed or second nadir at about 21 d (carboplatin, for example) (1). Neutrophil counts usually rebound from the nadir within 1 to 3 d. Immature granulocytes are an indicator for return of granulocytic activity. Animals with < 1000 neutrophils/μL are at an increased risk for sepsis and require close monitoring. Neutrophil counts < 500/μL (categorized as a grade 4 neutropenia) usually are associated with fever and sepsis (1). In addition to lower neutrophil counts, chemotherapy can result in gastrointestinal epithelial desquamation, and the combination of these factors can lead to increased opportunity for enteric bacteria to enter the circulation causing septicemia, with fewer phagocytic neutrophils to effectively clear the infection which can be life-threatening.