Adjuvant Carboplatin and Gemcitabine Combination Chemotherapy Postamputation in Canine Appendicular Osteosarcoma

Abstract

Background Appendicular osteosarcoma (OSA), the most common bone tumor in dogs, is typically treated by amputation and adjuvant chemotherapy. Despite numerous efforts, the median survival time (MST) for dogs receiving a platinum compound, doxorubicin, or a combination of these remains at 8–12 months. Evidence from studies in mice suggests that gemcitabine has activity against OSA in vivo. Our preliminary work demonstrated that the addition of low-dosage (10mM) gemcitabine to carboplatin resulted in synergistic inhibition of OSA cell viability in vitro. Objective The purpose of the following study was to determine whether the addition of low-dosage (2 mg/kg) gemcitabine to carboplatin chemotherapy in dogs with OSA after amputation would improve MST over carboplatin monotherapy. Animals Fifty dogs with histologically confirmed appendicular OSA. Methods Dogs were treated prospectively with amputation and up to 4 dosages of carboplatin and gemcitabine in combination every 3 weeks. Results The chemotherapeutic regimen was well tolerated with only 5 episodes of grade 3 or 4 hematologic toxicity. The median disease-free interval (DFI) was 203 days and the MST was 279 for all dogs in this study. The 1- and 2-year survival rates were 29.5 and 11.3%, respectively. Dogs with proximal humeral OSA had a shorter median DFI (P = .04) compared with dogs with OSA in other locations. Conclusions and Clinical Importance These results are comparable to those reported for carboplatin monotherapy indicating that the addition of gemcitabine to carboplatin in dogs with appendicular OSA does not appear to improve outcome.

Osteosarcoma in Dogs: Diagnosis and Treatment - A Literature Review

“…There was trend was observed in these studies in order to improve the chemotherapy response using a combination of different drugs, as reported in the studies by Chun et al [11], Bailey et al [19], McMahon et al [12], and Selmic et al [19]. Chun et al [11] consider that chemotherapy is promising when using cisplatin and doxorubicin, but suggest a study with a larger number of animals.…”

“…These are: Chen at. Al [2][3][4][5][7][8][9][10][11][12][13][14]. The animals described in this review, the animals were middle aged to elderly and medium to large size, except for one case of a Maltese dog reported by Teixeira et al [18].…”

“…One hypothesis when comparing these three studies is that cisplatin has a greater therapeutic effect. McMahon et al [12], in turn, used carboplatin association with gemcitabine, which is indicated for the treatment of bladder cancer and locally advanced or metastatic pancreatic adenocarcinoma. In addition, it is assumed that its cytotoxic action is related to the inhibition of DNA synthesis.28 Additionally to these studies, DeRegis et al [24] evaluated that initiating chemotherapy two or ten days after surgery did not improve the prognosis of patients and alert for the search of a safe starting dose in order to reduce toxicity.…”

Agentes Antineoplásicos Para O Tratamento Do Osteossarcoma

“…Notou-se que essa associação não promoveu melhorias na taxa de sobrevivência dos animais (MCMAHON et al 2011).…”

“…É também utilizado no tratamento de doenças auto-imunes, e atua na inibição da enzima dihidrofolatoredutase (MCMAHON et al 2011). Possui efeitos adversos que incluem a disfunção renal, pela dificuldade de excreção do quimioterápico, podendo levar ao desenvolvimento de insuficiência renal aguda em alguns pacientes, caso haja precipitação e acúmulo de metabólitos nos túbulos renais.…”