Toxicity of cytarabine constant rate infusion in dogs with high‐grade non‐Hodgkin lymphoma with bone marrow or central nervous system involvement

Abstract

Objective Cytarabine, a cell‐cycle phase‐specific antimetabolite, has been reported to improve outcomes in dogs with bone marrow (BM) or central nervous system (CNS) lymphoma involvement receiving combination chemotherapy. The objective of this study was to evaluate the incidence and severity of toxicity of cytarabine constant rate infusion (CRI) in dogs with high‐grade non‐Hodgkin lymphoma. Methods Medical records of canine lymphoma patients with confirmed or suspected BM (group 1) or CNS (group 2) involvement, treated with a modified cyclophosphamide, epirubicin, vincristine and prednisolone protocol, including a single dose of cytarabine given as CRI, were reviewed and adverse events graded. Results Twenty‐six dogs were included. Gastrointestinal toxicity occurred in 17 dogs (65.3%), with 5 (19.2%) experiencing grade III or IV toxicity. Neutropenia occurred in nine dogs (34.6%), but was grade I or II in most cases. Three dogs (11.5%) had thrombocytopenia: one grade III and two grade IV. Four dogs (15.3%) experienced increases in alanine amino transferase: one each grade I and II and two grade III. Five dogs (19.2%) required hospitalisation to manage toxicity after completing cytarabine CRI, and haematological toxicity resulted in treatment delays in five dogs (median delay of 4 days, range: 3–7 days). Conclusion Our findings suggest that gastrointestinal toxicity should be expected in lymphoma patients undergoing cytarabine CRI.

Are severe adverse events commonly observed in dogs during cancer chemotherapy? A retrospective study on 155 dogs

“…In other studies, focusing on particular molecules or protocols, the rate of dogs experiencing AE ranged from 20% to 81%. [25][26][27]32,[47][48][49][50] The total rate of AE following chemotherapy was 80% in our study, close to the upper bound of this range. One explicative reason could be the absence of systematic use of prophylactic medications in our institution.…”

“…In our study, 29.7% of dogs presented grade 1 AE, while grade 2–5 were reported in 6.5%, 41.3%, 21.9% and 0.6% of dogs, respectively. In other studies, focusing on particular molecules or protocols, the rate of dogs experiencing AE ranged from 20% to 81% 25–27,32,47–50 . The total rate of AE following chemotherapy was 80% in our study, close to the upper bound of this range.…”

“…6,26,[47][48][49][50] Gastrointestinal sAE frequencies were poorly documented but seemed quite rare. 6,26,27 In the study of Cunha et al, 2% of dogs exhibited vomiting of grade 2 or higher, 3% had diarrhoea of grade 2 or higher and inappetence of grade 3 or higher was observed in 2%. 6 In our study, 23 (14.8%) dogs had gastrointestinal sAE but contrary to some studies, including the study of Cunha et al, systematic prophylactic medications were not used.…”

“…Knowledge on incidence of sAE essentially comes from clinical trials that focused only on a single molecule or protocol. In these studies, description of AE is heterogeneous and evaluation of overall incidence of AE is beyond their scope 6–33 . The largest retrospective study dealing with overall frequency of AE included 292 cases, with digestive and haematological AE occurring in 20%–22% of dogs, 83% of which were grade 1 toxicities.…”

Cytosine arabinoside constant rate infusion without subsequent subcutaneous injections for the treatment of dogs with meningoencephalomyelitis of unknown origin

“…CA is considered to be a safe therapy in dogs with MUO, with only minimal adverse effects reported in previous studies 2–6 10. Localised alopecia, dermatitis, calcinosis cutis and deep pyoderma have been described in rare cases with the subcutaneous route of administration of CA,3 13 whereas gastrointestinal toxicity and myelosuppression are more common with high doses (300–600 mg/m 2 ) of CA administered by CRI 14 15. No adverse effects have been reported following a single CA CRI at the dose of 100–200 mg/m 2 , 6 9–12 which was also observed in the dogs in our study.…”