Double-blind placebo-controlled trial of adjuvant pamidronate with palliative radiotherapy and intravenous doxorubicin for canine appendicular osteosarcoma bone pain.
BACKGROUND
Canine osteosarcoma (OSA) causes focal malignant osteolysis leading to severe pain. Despite the documented efficacy of radiotherapy or IV aminobisphosphonates for managing cancer bone pain, their potential combined therapeutic value has not been reported in OSA-bearing dogs.


OBJECTIVE
Pamidronate combined with standardized palliative therapy will improve pain control and bone biologic effects in OSA-bearing dogs.


METHODS
Fifty dogs with appendicular OSA treated with standardized palliative therapy and either pamidronate or sterile saline.


METHODS
Randomized, prospective, double-blinded, placebo-controlled study. Treatment responses for dogs receiving standardized palliative therapy with (n = 26) or without (n = 24) adjuvant pamidronate were serially evaluated for changes in subjective pain scores, urine N-telopeptide (NTx) excretion, primary tumor relative bone mineral density (rBMD), and computerized pressure platform gait analysis.


RESULTS
Median duration of subjective pain relief for dogs treated with adjuvant pamidronate or placebo was 76 and 75 days, respectively (P= .39). Forty percent (20/50; pamidronate [11/26] and placebo [9/24]) of dogs experienced durable analgesia, defined by pain alleviation > or =112 days. For patients achieving durable pain control, dogs treated with pamidronate achieved greater reductions in NTx excretion and larger increases in rBMD compared with placebo controls. Changes in peak vertical force assessed by computerized pressure platform gait analysis correlated with pain alleviation in OSA-bearing dogs.


CONCLUSIONS
Combining pamidronate with standardized palliative therapy is safe, but does not clearly improve pain alleviation. However, in dogs achieving durable pain control, adjuvant pamidronate appears to decrease focal bone resorption in the local tumor microenvironment.
Fan
T M
TM
Department of Veterinary Clinical Medicine, University of Illinois at Urbana-Champaign, Urbana, IL, USA. t-fan@uiuc.edu
Charney
S C
SC
de Lorimier
L P
LP
Garrett
L D
LD
Griffon
D J
DJ
Gordon-Evans
W J
WJ
Wypij
J M
JM
D000698:Analgesia / Q000662:veterinary; D000700:Analgesics / Q000008:administration & dosage / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000627:therapeutic use; D004164:Diphosphonates / Q000008:administration & dosage* / Q000627:therapeutic use*; D004283:Dog Diseases / Q000188:drug therapy / Q000532:radiotherapy; D004285:Dogs; D004311:Double-Blind Method; D004317:Doxorubicin / Q000008:administration & dosage* / Q000627:therapeutic use*; D005121:Extremities / Q000473:pathology; D005260:Female; D008297:Male; D012516:Osteosarcoma / Q000150:complications / Q000662:veterinary; D059408:Pain Management; D000077268:Pamidronate; D011878:Radiotherapy / Q000662:veterinary*
D000700:Analgesics; D000970:Antineoplastic Agents; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D004317:Doxorubicin; D000077268:Pamidronate