Aftershocks of cancer treatment: Managing side effects (Proceedings)

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Aftershocks of cancer treatment: Managing side effects (Proceedings)

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Aug 01, 2009

The majority of cytotoxic chemotherapy protocols in common veterinary use are designed to have a low risk of adverse effects. In general, less than 1 in 4 animals will have unpleasant adverse effects and only approximately 5% will have a serious adverse event, leading to hospitalization. With appropriate intervention, the risk of a treatment-associated fatality is less than 1 in 200. Should serious side effects occur, doses can be reduced, drugs can be substituted, or additional medications dispensed to minimize the likelihood of further adverse effects. These changes are effective 90% of the time.

Even in practices where chemotherapy is not administered, referring and emergency/critical care practices are often called upon to deal with adverse effects resulting from cancer therapy that may have been administered at another clinic. Having a protocol in place for the treatment of these patients dramatically increases the likelihood of a good outcome should a serious adverse event be encountered.

The most commonly encountered adverse effects, neutropenia and gastrointestinal disturbance, generally occur as a result of "collateral damage" done to rapidly dividing cells by the cytotoxic agent. Both bone marrow stem cells and gastrointestinal crypt cells are rapidly dividing and thus sensitive to the antiproliferative effects of chemotherapy.

Neutropenia and sepsis

Neutropenia is a relatively common side effect of chemotherapy in companion animals and humans. In certain malignancies, bone marrow infiltration or other conditions can exacerbate myelosuppression. The severity of neutropenia and associated sepsis can be extremely variable, ranging from clinically silent to overwhelming and occasionally fatal.

Presenting Complaints: Many animals may be mildly or moderately neutropenic, yet show no outward signs of illness. Most companion animals have a relatively low risk of infection if their neutrophil count remains greater than 1,000/uL. It is important to remember that likelihood of infection and subsequent treatment decisions should be made based on absolute neutrophil count, not total white blood cell count.

Septic patients will typically present with vague, nonspecific signs of illness such as lethargy, weakness, and inappetence. They are often febrile, but a normal temperature does not rule out the presence of a serious or even life-threatening infection. An accurate medication history is very important, as the timing of the last chemotherapy treatment can help to determine if myelosuppression is likely. Neutropenia is likely to be seen 7-10 days after the administration of most chemotherapy drugs. Exceptions to this rule include vinblastine and paclitaxel, which can cause neutropenia as early as 4-5 days after administration, and lomustine (CCNU) and carboplatin, which can occasionally cause neutropenia as late as 2-3 weeks following administration.

Diagnostics: Septic patients are often febrile, as mentioned above. Other physical abnormalities could include tachycardia, injected mucous membranes, slow or prolonged capillary refill, or weak pulses. Initial minimum database should include a CBC and platelet count with manual differential, serum biochemistry profile, and urinalysis. Common changes include neutropenia with or without a left shift or toxic changes, thrombocytopenia, hyper- or hypoglycemia, evidence of dehydration, or metabolic acidosis. Urinalysis may reveal a quiet sediment, however urinary tract infections cannot be ruled out as neutropenia can result in the absence of neutrophils in the urine. Many clinicians will empirically culture the urine of neutropenic, septic patients. A coagulation profile is indicated in an animal with unquestionable signs of septic shock, as varying degrees of disseminated intravascular coagulation can be seen and must be treated aggressively. In animals presenting with respiratory signs or with a history of vomiting prior to presentation, thoracic radiographs to identify a nidus of infection are indicated. Recent human studies suggest that there is no benefit to obtaining "screening" thoracic radiographs in the asymptomatic neutropenic, septic patient.

Treatment: Asymptomatic patients with less than 1,000 neutrophils/uL can be managed on an outpatient basis. In these patients, the risk of nosocomial infection likely outweighs the benefit associated with hospitalization. A broad-spectrum oral antibiotic such as trimethoprim-sulfa (7.5 mg/kg BID), Clavamox (13.75 mg/kg BID) or enrofloxacin (5-10 mg/kg SID) should be prescribed for a 5-7 day course, and the owner should be instructed to monitor the patient's temperature once or twice daily at home. If the patient becomes clinically ill or the temperature exceeds 103.5oC, hospitalization may be required. Patients with mild neutropenia (>1,000/uL) generally require no treatment.