Adjuvant gemcitabine after surgical removal of aggressive malignant mammary tumours in dogs

Abstract

Canine mammary tumours are generally treated with surgery alone, despite the fact that 50% of them are malignant and many will eventually lead to recurrence or metastases. A prospective clinical trial in which dogs with aggressive mammary carcinoma of clinical stages IV and V were treated with surgical excision (n = 9) or with surgery and adjuvant weekly gemcitabine (n = 10) for at least four cycles was conducted. Gemcitabine was given as an intravenous infusion at the dose of 800 mg m(-2). Aim of the study was to explore potential beneficial effects of gemcitabine on time to local recurrence (TTR), time to distant metastases (TTM) and overall survival (OS) in canine patients with operated mammary tumours bearing high risk for locoregional failure and distant metastases. Also, factors associated with OS, including neutering status, body weight, age, clinical stage at presentation, tumour size, histological grade and, in dogs receiving chemotherapy, the number of gemcitabine treatments, were investigated. Finally, acute toxicities related to chemotherapy and quality of life were assessed in dogs receiving gemcitabine. Dogs treated with surgery alone or surgery followed by gemcitabine had no difference in TTR, TTM or OS (P > 0.05). In the group of dogs receiving adjuvant chemotherapy, the number of gemcitabine treatments was positively correlated with OS (P = 0.017). Gemcitabine treatment was well tolerated, with no dogs experiencing clinically relevant haematological or gastrointestinal toxicity. Despite being safe at the present dose, gemcitabine chemotherapy as an adjunct treatment to surgical excision may not be recommended in dogs with aggressive mammary carcinoma.

Prognostic factors for dogs with mammary inflammatory carcinoma: 43 cases (2003–2008)

“…[12][13][14] In women with IC, use of multiagent chemotherapeutic protocols has been shown to improve outcome, 8,15,16 and medical treatment (ie, administration of piroxicam, chemotherapeutic drugs, or both) showed some promise in prolonging survival times among dogs in the present study. Because mammary IC is generally considered a rapidly progressive disease in dogs, medical treatment is usually not attempted, and there is debate about the role of chemotherapy in the management of mammary carcinoma as a whole.…”

First-line metronomic chemotherapy in a metastatic model of spontaneous canine tumours: a pilot study

“…Indeed, animals at these advanced stages of disease are usually euthanized because of the very short survival even after a palliative surgery (less than 2-3 months) [18,19]. For this reason, the enrollment of an untreated group (control) of animals has not been ethically allowed.…”

“…For example, it has been recently published that the palliative surgery of aggressive malignant mammary tumours (stage IV e V) obtained a median overall survival of just 1.29 months [18]. For this reason, the enrollment of an "untreated" group (control or placebo) of animals or a treatment at the maximum tolerated dose with relevant and certain toxicities has not been ethically allowed in our study.…”

Tumors of the Mammary Gland

“…Most of the evidence regarding the efficacy of adjuvant chemotherapy is weak. 136 Adequately powered, randomized prospective trials are needed to determine the future role of adjuvant chemotherapy in dogs with high-risk mammary tumors. 131 Today, anthracycline or taxane combinations are considered part of first-line protocols in human breast cancer therapy in women requiring adjuvant therapy 75,[132][133][134] ; however, only inadequately powered studies on the efficacy of doxorubicin or docetaxel in dogs with mammary tumors exist and they did not establish benefit.…”