Clinical outcome of dogs diagnosed with canine inflammatory mammary cancer treated with metronomic cyclophosphamide, a cyclooxygenase‐2 inhibitor and toceranib phosphate

Abstract

Canine inflammatory mammary cancer (IMC) is highly malignant, invasive and a therapeutic challenge, because effective medical treatment is still unavailable. This retrospective study compares the efficacy of an oral cyclooxygenase‐2 (COX‐2) inhibitor combined with toceranib phosphate and oral cyclophosphamide (multi‐drug therapy [MT]) with COX‐2 inhibitor therapy alone (single‐drug therapy [ST]) in dogs diagnosed with secondary IMC. Clinical response, adverse events, overall survival time (OST), disease‐free survival (DFS) and time to progression (TTP) were evaluated. Sixteen patients were included, eight received MT and eight receiving ST. Median OST was significantly higher in patients receiving MT (96.0 vs. 37.5 days; p = .046) and in patients with post‐surgical rather than non‐surgical IMC (86.5 vs. 41.5 days; p = .038). Additionally, median TTP was significantly higher in patients treated with MT (p = .010). In patients with non‐surgical IMC, the clinical benefit (CB) was reached in 100% (n = 3) of patients receiving MT and in 33% (n = 1) of those receiving ST; the response duration was significantly longer in MT cases (p = .026). The absence of disease progression at day 30 of treatment was significantly associated with longer OST, DFS and TTP (p = .018, p = .002 and p < .001, respectively). Adverse events occurred more frequently in patients treated with MT compared with ST (p = .026). The MT protocol produced primarily mild to moderate toxicities, which were resolved with supportive care; therefore, the combination of drugs was adequately tolerated by most of the patients. The combination of toceranib, a COX‐2 inhibitor and oral cyclophosphamide may be a protocol with potential therapeutic efficacy for dogs with IMC.

Pharmacokinetics of Carboplatin in Combination with Low-Dose Cyclophosphamide in Female Dogs with Mammary Carcinoma

“…Metronomic chemotherapy is emerging as a promising alternative that results in fewer adverse reactions and lower stress levels [ 6 ]. However, in veterinary medicine, there are still few studies related to its effectiveness, whether it is isolated or associated with conventional chemotherapy, especially in the case of mammary tumors in female dogs [ 7 , 8 , 9 , 10 ]. Nevertheless, the clinical implementation of new treatment combinations with low-dose chemotherapy requires studies to select effective treatment combinations for each tumor type and population [ 8 , 11 , 12 , 13 ].…”

A phase II study of a doublet metronomic chemotherapy regimen consisting of oral vinorelbine and capecitabine in Chinese women with HER2‐negative metastatic breast cancer

“…A recent study showed that metronomic chemotherapy (5‐fluorouracil + VNR) cotargeting TNBC cells and endothelial cells effectively inhibits cell regrowth and migration via FAK/VEGFR2/VEGF downregulation and autophagy/apoptosis activation 30 . Owing to the diverse antitumor mechanisms of metronomic chemotherapy, a growing number of studies are currently endeavoring to integrate metronomic chemotherapy with other interventions, including targeted therapy and immunotherapy, among others, for the purpose of treating tumors 31–35 . In recent years, metronomic chemotherapy has gained widespread application in a range of cancers, including BC, 36,37 esophageal and gastroesophageal cancer, 38 lung cancer, 39 pancreatic cancer, 40 ovarian cancer, 41 and others.…”

Mammary carcinoma: Comparative oncology between small animals and humans—New therapeutic tools

“…In women with BC, multimodal (adjuvant or neoadjuvant) chemotherapy uses anthracyclins (doxorubicin, epirubicin), taxanes (paclitaxel, docetaxel) and cyclophosphamide (Pernaut et al, 2018). In small animals with MCs, apart from canine inflammatory MCs, chemotherapy is rarely multimodal, which may contribute to the limited results obtained so far in terms of survival improvement (Alonso‐Miguel et al, 2022; Petrucci et al, 2021; Valdivia et al, 2021). A progress in canine/feline MC therapy can be expected by further developments in multimodal chemotherapy.…”