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

被引：45

作者：

London, Cheryl A. ^{[1
,2
]}

Gardner, Heather L. ^{[1
,2
]}

Mathie, Tamra ^{[1
,2
]}

Stingle, Nicole ^{[1
,2
]}

Portela, Roberta ^{[3
]}

Pennell, Michael L. ^{[4
]}

Clifford, Craig A. ^{[5
]}

Rosenberg, Mona P. ^{[6
]}

Vail, David M. ^{[7
]}

Williams, Laurel E. ^{[8
]}

Cronin, Kim L. ^{[9
]}

Wilson-Robles, Heather ^{[10
]}

Borgatti, Antonella ^{[11
]}

Henry, Carolyn J. ^{[12
]}

Balley, Dennis B. ^{[13
]}

Locke, Jennifer ^{[14
]}

Northrup, Nicole C. ^{[15
]}

Crawford-Jakubiak, Martin ^{[16
]}

Gill, Virginia L. ^{[17
]}

Klein, Mary K. ^{[18
]}

Ruslander, David M. ^{[19
]}

Thamm, Doug H. ^{[20
]}

Phillips, Brenda ^{[21
]}

Post, Gerald ^{[22
]}

机构：

[1] Ohio State Univ, Coll Vet Med, Dept Vet Biosci, Columbus, OH 43210 USA

[2] Ohio State Univ, Coll Vet Med, Dept Vet Clin Sci, Columbus, OH 43210 USA

[3] Univ Illinois, Coll Vet Med, Dept Vet Clin Med, Champaign, IL USA

[4] Ohio State Univ, Coll Publ Hlth, Div Biostat, Columbus, OH 43210 USA

[5] Hope Vet Specialists, Malvern, PA USA

[6] Vet Canc Grp, Tustin, CA USA

[7] Univ Wisconsin, Sch Vet Med, Dept Med Sci, Madison, WI 53706 USA

[8] N Carolina State Univ, Coll Vet Med, Dept Clin Sci, Raleigh, NC USA

[9] New England Vet Oncol Grp, Waltham, MA USA

[10] Texas A&M Univ, Coll Vet Med, Dept Small Anim Clin Sci, College Stn, TX 77843 USA

[11] Univ Minnesota, Coll Vet Med, Dept Vet Clin Sci, St Paul, MN 55108 USA

[12] Univ Missouri, Coll Vet Med, Dept Vet Med & Surg, Columbia, MO 65211 USA

[13] Oradell Anim Hosp, Paramus, NJ USA

[14] Southeast Vet Oncol & Med, Orange, FL USA

[15] Univ Georgia, Coll Vet Med, Dept Small Anim Med & Surg, Athens, GA USA

[16] Sage Ctr Vet Specialty & Emergency Care, Concord, CA USA

[17] VCA Katonah Bedford Vet Ctr, Bedford, NY USA

[18] Southwest Vet Oncol, Tucson, AZ USA

[19] Vet Specialty Hosp Carolinas, Cary, NC USA

[20] Colorado State Univ, Coll Vet Med & Biomed Sci, Dept Clin Sci, Ft Collins, CO 80523 USA

[21] Vet Specialty Hosp San Diego, San Diego, CA USA

[22] Vet Canc Ctr, Norwalk, CT USA

来源：

PLOS ONE | 2015年 / 10卷 / 04期

关键词：

ENDOTHELIAL GROWTH-FACTOR; DOXORUBICIN COMBINATION CHEMOTHERAPY; TYROSINE KINASE INHIBITOR; LOW-DOSE CYCLOPHOSPHAMIDE; REGULATORY T-CELLS; METRONOMIC CHEMOTHERAPY; CANINE OSTEOSARCOMA; SOLID TUMORS; ORAL CYCLOPHOSPHAMIDE; ADJUVANT CARBOPLATIN;

D O I：

10.1371/journal.pone.0124889

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 toceranibtreated 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.

引用

页数：17

共 1 条

[1] Evaluation of metronomic cyclophosphamide chemotherapy as maintenance treatment for dogs with appendicular osteosarcoma following limb amputation and carboplatin chemotherapy
Matsuyama, Arata
Schott, Courtney R.
Wood, Geoffrey A.
Richardson, Danielle
Woods, J. Paul
Mutsaers, Anthony J.
JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION, 2018, 252 (11): : 1377 - 1383

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