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Impact of Toceranib/Piroxicam/Cyclophosphamide Maintenance Therapy on Outcome of Dogs with Appendicular Osteosarcoma following Amputation and Carboplatin Chemotherapy: A Multi-Institutional Study.

London CA, Gardner HL, Mathie T, Stingle N, Portela R, Pennell ML, Clifford CA, Rosenberg MP, Vail DM, Williams LE, Cronin KL, Wilson-Robles H, Borgatti A, Henry CJ, Bailey DB, Locke J, Northrup NC, Crawford-Jakubiak M, Gill VL, Klein MK, Ruslander DM, Thamm DH, Phillips B, Post G - PLoS ONE (2015)

Bottom Line: We hypothesized that the addition of toceranib to metronomic cyclophosphamide/piroxicam therapy would significantly improve disease-free interval (DFI) and overall survival (OS) in dogs with appendicular osteosarcoma (OSA) following amputation and carboplatin chemotherapy.Patient demographics were not significantly different between both groups.The addition of toceranib to metronomic piroxicam/cyclophosphamide therapy following amputation and carboplatin chemotherapy did not improve median DFI, OS or the 1-year survival rate in dogs with OSA.

View Article: PubMed Central - PubMed

Affiliation: Departments of Veterinary Biosciences and Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio, United States of America.

ABSTRACT

Background: We hypothesized that the addition of toceranib to metronomic cyclophosphamide/piroxicam therapy would significantly improve disease-free interval (DFI) and overall survival (OS) in dogs with appendicular osteosarcoma (OSA) following amputation and carboplatin chemotherapy.

Methods and findings: This was a randomized, prospective clinical trial in which dogs with OSA free of gross metastatic disease (n = 126) received carboplatin chemotherapy (4 doses) following amputation. On study entry, dogs were randomized to receive piroxicam/cyclophosphamide with or without toceranib (n = 63 each) after completing chemotherapy. Patient demographics were not significantly different between both groups. During or immediately following carboplatin chemotherapy, 32 dogs (n = 13 toceranib; n = 19 control) developed metastatic disease, and 13 dogs left the study due to other medical conditions or owner preference. Following carboplatin chemotherapy, 81 dogs (n = 46 toceranib; n = 35 control) received the metronomic treatment; 35 dogs (n = 20 toceranib; n = 15 control) developed metastatic disease during the maintenance therapy, and 26 dogs left the study due to other medical conditions or owner preference. Nine toceranib-treated and 11 control dogs completed the study without evidence of metastatic disease 1-year following amputation. Toceranib-treated dogs experienced more episodes of diarrhea, neutropenia and weight loss than control dogs, although these toxicities were low-grade and typically resolved with supportive care. More toceranib-treated dogs (n = 8) were removed from the study for therapy-associated adverse events compared to control dogs (n = 1). The median DFI for control and toceranib treated dogs was 215 and 233 days, respectively (p = 0.274); the median OS for control and toceranib treated dogs was 242 and 318 days, respectively (p = 0.08). The one year survival rate for control dogs was 35% compared to 38% for dogs receiving toceranib.

Conclusions: The addition of toceranib to metronomic piroxicam/cyclophosphamide therapy following amputation and carboplatin chemotherapy did not improve median DFI, OS or the 1-year survival rate in dogs with OSA.

No MeSH data available.


Related in: MedlinePlus

Disease Free Interval.Kaplan-Meier disease-free interval (DFI) curves comparing dogs treated with toceranib to control dogs. Hash marks denote censored observations; n = 63 toceranib-treated dogs; n = 63 control dogs. (A) Intent-to-treat analysis (p = 0.274). (B) Adherence analysis (p = 0.3).
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pone.0124889.g001: Disease Free Interval.Kaplan-Meier disease-free interval (DFI) curves comparing dogs treated with toceranib to control dogs. Hash marks denote censored observations; n = 63 toceranib-treated dogs; n = 63 control dogs. (A) Intent-to-treat analysis (p = 0.274). (B) Adherence analysis (p = 0.3).

Mentions: The median DFI reported in the intent-to-treat analysis was 233 days for toceranib-treated dogs and 215 days for control dogs (p = 0.274, Fig 1A, Tables 2 and 3). The median DFI reported in the adherence analysis was 223 days for toceranib-treated dogs and 198 days for control dogs (p = 0.3, Fig 1B, Tables 2 and 3). The median OS was 318 days and 242 days for toceranib-treated and control dogs, respectively (p = 0.08) (Fig 2, Tables 2 and 3). DFI was similar across treatment groups, however there was a time-dependent difference in short-term mortality risk (Fig 2 and Table 3). Initially, the mortality hazard was greater among control patients, but at approximately 400 days the risks converged and were not significantly different at one year (p = 0.961) and two years (p = 0.316). The 1- and 2-year survival rates of toceranib treated group were not significantly different from those of the control group (p = 0.963 and 0.325, respectively) (Table 2). Median DFI (182 days, p = 0.281) and OS (243 days, p = 0.28) were shorter among patients whose cancer was located in the proximal humerus, but this difference was not significant (Table 4). In addition, proximal humeral location did not affect the differences between treatment groups (p > 0.28 for each survival outcome).


Impact of Toceranib/Piroxicam/Cyclophosphamide Maintenance Therapy on Outcome of Dogs with Appendicular Osteosarcoma following Amputation and Carboplatin Chemotherapy: A Multi-Institutional Study.

London CA, Gardner HL, Mathie T, Stingle N, Portela R, Pennell ML, Clifford CA, Rosenberg MP, Vail DM, Williams LE, Cronin KL, Wilson-Robles H, Borgatti A, Henry CJ, Bailey DB, Locke J, Northrup NC, Crawford-Jakubiak M, Gill VL, Klein MK, Ruslander DM, Thamm DH, Phillips B, Post G - PLoS ONE (2015)

Disease Free Interval.Kaplan-Meier disease-free interval (DFI) curves comparing dogs treated with toceranib to control dogs. Hash marks denote censored observations; n = 63 toceranib-treated dogs; n = 63 control dogs. (A) Intent-to-treat analysis (p = 0.274). (B) Adherence analysis (p = 0.3).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4414350&req=5

pone.0124889.g001: Disease Free Interval.Kaplan-Meier disease-free interval (DFI) curves comparing dogs treated with toceranib to control dogs. Hash marks denote censored observations; n = 63 toceranib-treated dogs; n = 63 control dogs. (A) Intent-to-treat analysis (p = 0.274). (B) Adherence analysis (p = 0.3).
Mentions: The median DFI reported in the intent-to-treat analysis was 233 days for toceranib-treated dogs and 215 days for control dogs (p = 0.274, Fig 1A, Tables 2 and 3). The median DFI reported in the adherence analysis was 223 days for toceranib-treated dogs and 198 days for control dogs (p = 0.3, Fig 1B, Tables 2 and 3). The median OS was 318 days and 242 days for toceranib-treated and control dogs, respectively (p = 0.08) (Fig 2, Tables 2 and 3). DFI was similar across treatment groups, however there was a time-dependent difference in short-term mortality risk (Fig 2 and Table 3). Initially, the mortality hazard was greater among control patients, but at approximately 400 days the risks converged and were not significantly different at one year (p = 0.961) and two years (p = 0.316). The 1- and 2-year survival rates of toceranib treated group were not significantly different from those of the control group (p = 0.963 and 0.325, respectively) (Table 2). Median DFI (182 days, p = 0.281) and OS (243 days, p = 0.28) were shorter among patients whose cancer was located in the proximal humerus, but this difference was not significant (Table 4). In addition, proximal humeral location did not affect the differences between treatment groups (p > 0.28 for each survival outcome).

Bottom Line: We hypothesized that the addition of toceranib to metronomic cyclophosphamide/piroxicam therapy would significantly improve disease-free interval (DFI) and overall survival (OS) in dogs with appendicular osteosarcoma (OSA) following amputation and carboplatin chemotherapy.Patient demographics were not significantly different between both groups.The addition of toceranib to metronomic piroxicam/cyclophosphamide therapy following amputation and carboplatin chemotherapy did not improve median DFI, OS or the 1-year survival rate in dogs with OSA.

View Article: PubMed Central - PubMed

Affiliation: Departments of Veterinary Biosciences and Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio, United States of America.

ABSTRACT

Background: We hypothesized that the addition of toceranib to metronomic cyclophosphamide/piroxicam therapy would significantly improve disease-free interval (DFI) and overall survival (OS) in dogs with appendicular osteosarcoma (OSA) following amputation and carboplatin chemotherapy.

Methods and findings: This was a randomized, prospective clinical trial in which dogs with OSA free of gross metastatic disease (n = 126) received carboplatin chemotherapy (4 doses) following amputation. On study entry, dogs were randomized to receive piroxicam/cyclophosphamide with or without toceranib (n = 63 each) after completing chemotherapy. Patient demographics were not significantly different between both groups. During or immediately following carboplatin chemotherapy, 32 dogs (n = 13 toceranib; n = 19 control) developed metastatic disease, and 13 dogs left the study due to other medical conditions or owner preference. Following carboplatin chemotherapy, 81 dogs (n = 46 toceranib; n = 35 control) received the metronomic treatment; 35 dogs (n = 20 toceranib; n = 15 control) developed metastatic disease during the maintenance therapy, and 26 dogs left the study due to other medical conditions or owner preference. Nine toceranib-treated and 11 control dogs completed the study without evidence of metastatic disease 1-year following amputation. Toceranib-treated dogs experienced more episodes of diarrhea, neutropenia and weight loss than control dogs, although these toxicities were low-grade and typically resolved with supportive care. More toceranib-treated dogs (n = 8) were removed from the study for therapy-associated adverse events compared to control dogs (n = 1). The median DFI for control and toceranib treated dogs was 215 and 233 days, respectively (p = 0.274); the median OS for control and toceranib treated dogs was 242 and 318 days, respectively (p = 0.08). The one year survival rate for control dogs was 35% compared to 38% for dogs receiving toceranib.

Conclusions: The addition of toceranib to metronomic piroxicam/cyclophosphamide therapy following amputation and carboplatin chemotherapy did not improve median DFI, OS or the 1-year survival rate in dogs with OSA.

No MeSH data available.


Related in: MedlinePlus