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

Abstract

Metronomic chemotherapy—the low-dose, long term and\ud \ud frequently administered chemotherapy—has revealed in\ud \ud these years an important impact on the stabilization of\ud \ud cancer disease for its known antiangiogenic effects,\ud \ud prolonged clinical benefits and the improved quality of life\ud \ud of several cancer patients, without any high grade toxicity\ud \ud [1–3]. Both the low cost and the oral administration of the\ud \ud drugs are key characteristics of this schedule and may offer\ud \ud important social advantages [4]. Anecdotical case reports\ud \ud [5–7] and experiences in small subsets of patients enrolled\ud \ud in retrospective clinical studies [8–10] on metastatic cancers\ud \ud have been recently published about the use of metronomic\ud \ud therapy as a first-line treatment. These point out the\ud \ud possible importance of metronomic chemotherapy as an\ud \ud alternative approach to first-line therapy in frail patients\ud \ud requiring palliation or patients refusing the standard\ud \ud chemotherapy for its impact on the quality of life. However,\ud \ud no data of prospective clinical trials on first line metronomic\ud \ud chemotherapy are currently available in metastatic\ud \ud cancer human patients.\ud \ud The veterinary medical oncology has advanced dramatically\ud \ud over the past few decades, because of the successful\ud \ud application of a number of conventional chemotherapeutic\ud \ud drugs to the cancer conditions diagnosed in veterinary\ud \ud patients [11]. Veterinary oncology cases often present a\ud \ud unique opportunity to investigate novel drugs and treatment\ud \ud schedules providing many in vivo information to the larger\ud \ud medical community and giving new effective options for\ud \ud dogs themselves [12]. As well recently pointed out by\ud \ud Paoloni and Khanna [13], these studies may also have a\ud \ud great translational relevance, predicting new therapies and\ud \ud related surrogate markers in human beings because pet dogs\ud \ud with cancers might assist the transition between mouse\ud \ud models and human patients. Moreover, in the clinical\ud \ud practice, veterinarians and their clients are generally less\ud \ud willing to accept a high degree of side effects, which most\ud \ud often results in lower drug doses than the ones that are used\ud \ud in human oncology.\ud \ud The aim of the present pilot study was to test a first-line\ud \ud metronomic oral combination of cyclophosphamide (CTX)\ud \ud and celecoxib (CXB) in canine metastatic spontaneous\ud \ud tumours, characterizing possible biomarkers to translate in\ud \ud human clinical research

Clinical Studies of Metronomic Chemotherapy in Dogs

“…In almost half the cases, lomustine was used in conjunction with an anti-infl ammatory drug; in 29 dogs an NSAID was used. Results obtained using this protocol were comparable to those [ 38 ], with a response rate of 36 %. The nonprogression of the disease, observed in approximately 30 % of cases, had a duration of about 137 days.…”

“…Fifteen dogs with various tumors with distant metastases were treated with metronomic chemotherapy as fi rst-line treatment [ 38 ]. The protocol consisted of daily administration of cyclophosphamide, 25 mg/m 2 , and celecoxib, 2 mg/kg.…”

Palliative care in small animal oncology

“…Metronomic chemotherapy is the administration of daily or every other day low-dose alkylating agents in combination with NSAIDs and has been evaluated in both the adjunctive and gross disease setting for various canine and feline neoplasms (Lana and others 2007, Burton and others 2011, Tripp and others 2011, Marchetti and others 2012, Leo and others 2014, London and others 2015). …”

Resumos Do Xvi Enapave

“…O exame histopatológico é o método que apresenta maior segurança no diagnóstico e permite uma caracterização biológica da doença (Bostock, 1986). O método mais utilizado para o estabelecimento do prognóstico é o sistema TNM, onde é levado em consideração o tamanho (T), os linfonodos regionais acometidos (N) e as metástases a distancia (M) (Owen, 1980). A cirurgia ainda é o método terapêutico mais eficiente permitindo até mesmo a cura completa da doença, caso não existam metástases a distância.…”