Evaluation of cisplatin combined with piroxicam for the treatment of oral malignant melanoma and oral squamous cell carcinoma in dogs.
OBJECTIVE
To determine the maximum tolerated dose (MTD) of cisplatin administered with piroxicam, the antitumor activity and toxicity of cisplatin combined with piroxicam in dogs with oral malignant melanoma (OMM) and oral squamous cell carcinoma (SCC), and the effects of piroxicam on the pharmacokinetics of cisplatin in dogs with tumors.


METHODS
Prospective nonrandomized clinical trial.


METHODS
25 dogs.


METHODS
Dogs were treated with a combination of cisplatin (escalating dose with 6 hours of diuresis with saline [0.9% NaCI] solution) and piroxicam (0.3 mg/kg 10.14 mg/lb], PO, q 24 h). The initial cisplatin dose (50 mg/m2) was increased by 5 mg/m2 until the MTD was reached. Tumor stage and size were determined at 6-week intervals during treatment. The pharmacokinetics of cisplatin were determined in dogs receiving a combination of cisplatin and piroxicam during the clinical trial and dogs that were treated with cisplatin alone.


RESULTS
11 dogs with OMM and 9 dogs with SCC were included in the clinical trial. The MTD of cisplatin when administered in combination with piroxicam was 50 mg/m2. Tumor remission occurred in 5 of 9 dogs with SCC and 2 of 11 dogs with OMM. The most common abnormality observed was renal toxicosis. Clearance of cisplatin in dogs that were treated with cisplatin alone was not significantly different from that in dogs treated with a combination of cisplatin and piroxicam.


CONCLUSIONS
Cisplatin administered in combination with piroxicam had antitumor activity against OMM and SCC. The level of toxicity was acceptable, although renal function must be monitored carefully.
Boria
Pedro A
PA
Purdue Comparative Oncology Program, Department of Veterinary Clinical Science, School of Veterinary Medicine, Purdue University, West Lafayette, IN 47907, USA.
Murry
Daryl J
DJ
Bennett
Peter F
PF
Glickman
Nita W
NW
Snyder
Paul W
PW
Merkel
Brenna L
BL
Schlittler
Deborah L
DL
Mutsaers
Anthony J
AJ
Thomas
Rose M
RM
Knapp
Deborah W
DW
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000662:veterinary*; D002945:Cisplatin / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004283:Dog Diseases / Q000188:drug therapy*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation / Q000662:veterinary; D004347:Drug Interactions; D005260:Female; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000662:veterinary*; D009062:Mouth Neoplasms / Q000188:drug therapy / Q000662:veterinary*; D010894:Piroxicam / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D011446:Prospective Studies; D012074:Remission Induction; D016896:Treatment Outcome
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D010894:Piroxicam; D002945:Cisplatin