A Retrospective Evaluation of Chemotherapy Overdoses in Dogs and Cats

Abstract

Chemotherapy overdoses (ODs) are severe complications that can occur following the use of antineoplastics. However, little is known about chemotherapy ODs in veterinary medicine. The goals of this retrospective study were to report the occurrence, type, and cause of known chemotherapy ODs in companion animal medicine. The American College of Veterinary Internal Medicine oncology and internal medicine listservs were solicited for chemotherapy OD cases in dogs and cats. An OD was defined as administration of a chemotherapy dose 10% higher than intended, or at a shorter interval than planned. Twelve non-anthracycline ODs in 11 dogs, and 3 cat ODs, were collected. Overdoses in dogs included carboplatin, cyclophosphamide, L-asparaginase, lomustine, mustargen, vincristine, and vinorelbine. The cat ODs included doxorubicin and vincristine. In dogs, the median OD was 2.1x (range: 1.2–10x) the intended dose. All dogs survived the OD and developed a variety of gastrointestinal and hematologic toxicities of varying grades. Both cats with a 2.4x vincristine OD died despite supportive care. The cat who received a 2x OD of doxorubicin survived the event, experiencing Veterinary Cooperative Oncology Group–common terminology criteria for adverse events (VCOG) grade I thrombocytopenia and anemia, and VCOG grade II neutropenia. Chemotherapy ODs appear to be rare in veterinary medicine and are typically 2–3xs the intended dose. Clinical effects include VCOG grade I and II gastrointestinal distress and VCOG grade III and IV hematologic effects. With appropriate supportive care, most patients will survive the event. Life-threatening events are more common in cats following vincristine ODs.

Complete recovery of a cyclophosphamide overdose after vincristine administration in a dog

“…As long as the MTD is not exceeded, most dogs presenting adverse events after the treatment with vincristine and cyclophosphamide have subclinical, mild, self-limiting and short-lasting complications. 6,18 However, an overdose may cause life-threatening consequences. [11][12][13][14] Cyclophosphamide can produce gastrointestinal toxicity (anorexia, diarrhea, vomiting), sterile haemorrhagic cystitis and myelosuppression.…”

“…15,16 In veterinary medicine, gastrointestinal toxicity (anorexia, diarrhoea, vomiting), sterile haemorrhagic cystitis and myelosuppression are the possible clinical adverse events associated with cyclophosphamide when used at a therapeutical dosage. 6,17 The same adverse events are seen when an overdose happens, but with higher severity. 6,[11][12][13] This case report describes for the first time a recovery after cyclophosphamide overdose produced immediately after the administration of another chemotherapeutic agent (vincristine) in an oncology patient; therefore, vincristine at therapeutic doses did not seem to add toxicity synergistically in this case.…”

“…In terms of vincristine, MTD as a single agent in dogs is 0.75 mg/m 2 . 6 To the authors' knowledge, this is the first publication that describes a chemotherapy overdose followed after the administration of other chemotherapeutic agent at a normal dose. For that reason, there is no information about synergistic toxicity or recovery times in this scenario.…”

“…1,7 Toxicities induced by chemotherapeutic agents overdose seems to be relatively uncommon in veterinary medicine, but have the potential to cause serious morbidities or mortalities. 6 In veterinary medicine, the information available is based on few case reports, being the majority of them a singleagent chemotherapy overdoses. 6 In human medicine, it is known that patients with cancer are at particular risk of having chemotherapy medical errors and severe toxicities because their physiological reserves might be compromised, the drugs have narrow therapeutic indices, the therapies require multiple dose adjustments and precise monitoring of laboratory parameters and many decisions are made by different interprofessional care teams that increases the risk of miscommunication.…”

“…In veterinary medicine, some strategies are implemented in referral hospitals, but not in the majority of small primary care practices. As it has been mentioned before, the incidence is low, but probably many more unreported cases may exist 6 . This premise has been proved in human medicine and the authors think that it applies to veterinary medicine as well, and this is why we should put an effort in reducing these accidents.…”