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 (10 mM) 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.
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 (10 mM) 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.
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Authors: Courtney R Schott; Latasha Ludwig; Anthony J Mutsaers; Robert A Foster; Geoffrey A Wood Journal: PLoS One Date: 2018-10-29 Impact factor: 3.240