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Clinical Trial
. 2011 May-Jun;25(3):511-7.
doi: 10.1111/j.1939-1676.2011.0697.x. Epub 2011 Apr 12.

Adjuvant carboplatin and gemcitabine combination chemotherapy postamputation in canine appendicular osteosarcoma

M McMahon  1 , T Mathie, N Stingle, E Romansik, D Vail, C London
Affiliations
Clinical Trial

Adjuvant carboplatin and gemcitabine combination chemotherapy postamputation in canine appendicular osteosarcoma

M McMahon et al. J Vet Intern Med. 2011 May-Jun.

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 (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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Figures

Fig. 1
Fig. 1
Kaplan-Meier disease-free interval (DFI) curves comparing dogs treated with carboplatin/gemcitabine to historical controls treated with carboplatin chemotherapy.
Fig. 2
Fig. 2
Kaplan-Meier overall survival (OS) curves comparing dogs treated with carboplatin/gemcitabine combination to historical controls treated with carboplatin chemotherapy.
Fig. 3
Fig. 3
Kaplan-Meier disease-free interval (DFI) curves for dogs with osteosarcoma (OSA) in the proximal humerus treated with amputation followed by carboplatin and gemcitabine chemotherapy versus dogs with OSA in other locations that underwent the same treatment (P = .04).
See this image and copyright information in PMC

References

    1. Withrow SJ, Vail DM. Withrow and MacEwen’s Small Animal Clinical Oncology. 4. St. Louis, MO: Saunders Elsevier; 2007. pp. 540–573.
    1. Spodnick GJ, Berg J, Rand WM, et al. Prognosis for dogs with appendicular osteosarcoma treated by amputation alone: 162 cases (1978–1988) J Am Vet Med Assoc. 1992;200:995–999. - PubMed
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    1. Bergman PJ, MacEwen EG, Kurzman ID, et al. Amputation and carboplatin for treatment of dogs with osteosarcoma: 48 cases (1991 to 1993) J Vet Intern Med. 1996;10:76–81. - PubMed
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