Evaluation of a multi‐agent chemotherapy protocol combining lomustine, procarbazine and prednisolone (LPP) for the treatment of relapsed canine non‐Hodgkin high‐grade lymphomas

Abstract

The standard of care treatment for canine lymphoma is multi-agent chemotherapy containing prednisolone, cyclophosphamide, vincristine and an anthracycline such as doxorubicin (CHOP) or epirubicin (CEOP). Lomustine, vincristine, procarbazine, and prednisone (LOPP) has been evaluated as a rescue, with encouraging results; however, resistance to vincristine is likely in patients relapsing on CHOP/CEOP, and this agent may enhance LOPP toxicity without improving efficacy. The aim of this study was to evaluate responses to a modified-LOPP protocol that does not include vincristine (LPP) and is administered on a 21-day cycle. Medical records of dogs with high-grade multicentric lymphoma from 2012 to 2017 were reviewed. Dogs with relapsed lymphoma that received LPP as a rescue protocol were enrolled. Response, time from initiation to discontinuation (TTD) and toxicity of LPP were assessed. Forty-one dogs were included. Twenty-five dogs (61%) responded to LPP including 12 complete responses (CR) and 13 partial responses (PR). Responders had a significantly longer TTD (P < .001) compared to non-responders with 84 days for CR and 58 days for PR. Neutropenia was documented in 20 dogs (57%): 12 grade I to II, 8 grade III to IV. Thrombocytopenia was infrequent (20%): 5 grade I to II, 2 grade III to IV. Twelve dogs developed gastrointestinal toxicity (30%): 10 grade I to II and 2 grade III. Nineteen dogs had elevated ALT (59%): 9 grade I to II, 10 grade III to IV. Treatment was discontinued due to toxicity in 8 dogs (19%). The LPP protocol shows acceptable efficacy and toxicity-profile and minimizes in-hospital procedures.

Evaluation of a multi‐agent chemotherapy protocol combining dexamethasone, melphalan, actinomycin D, and cytarabine for the treatment of resistant canine non‐Hodgkin high‐grade lymphomas: a single centre's experience

“…A complete response (CR) was defined as disappearance of all measurable disease (ie, lymph nodes palpably normal), a partial response (PR) defined as >50% but <100% reduction in measurable disease, stable disease (SD) was defined as <50% reduction or < 25% increase in measurable disease, and (PD) was defined as >25% increase in measurable disease or appearance of new lesions. 15 As documented, measurements were not available in all dogs, and dogs that were noted by the attending clinician to have a CR or PR in their clinical records were also classified as responders. To be classified as responders, clinical response had to persist for at least 14 days, dogs who responded to week 1 of the protocol but then progressed in week 2 were classified as having PD.…”

“…Several single-agent and multiagent rescue protocols are described; response rates are highly variable (18%-77%) and remission durations are shorter in comparison to first-line treatment (56-238 days). [11][12][13][14][15][16][17][18][19][20][21][22][23] Evaluation of the efficacy and tolerability of rescue protocols is limited by the relatively small number of cases in comparison with studies of first-line protocols and the significant variability in the degree of pre-treatment.…”

Subcutaneous B Cell Lymphoma in a Dog from the West Indies

“…Since lymphoma is a systemic disease, treatment for multicentric and cutaneous lymphoma involves systemic chemotherapy [2,12,20]. The best response rates have been seen when using multidrug protocols incorporating doxorubicin [1,2,12]; however, in cases of cutaneous lymphoma, responses to treatment may be short lived. Surgical excision may also be recommended for solitary nodules [12], and radiation therapy can be used to try to control local disease [6].…”

“…In middle-aged dogs, lymphoma is one of the most common types of cancer diagnosed [1,2]. Multicentric lymph node involvement is the most common, but other forms include cranial mediastinal, gastrointestinal, cutaneous, and other extranodal forms [2].…”

“…Multicentric lymph node involvement is the most common, but other forms include cranial mediastinal, gastrointestinal, cutaneous, and other extranodal forms [2]. Approximately 65-75% of canine multicentric lymphomas are B cell mediated [1]; however, canine lymphoma may also be T cell mediated [2].…”