OBJECTIVE To conduct a phase I-II clinical trial of hyaluronan-cisplatin nanoconjugate (HA-Pt) in dogs with naturally occurring malignant tumors.
ANIMALS 18 healthy rats, 9 healthy mice, and 16 dogs with cancer.
PROCEDURES HA-Pt was prepared and tested by inductively coupled plasma mass spectrometry; DNA-platinum adduct formation and antiproliferation effects of cisplatin and HA-Pt were compared in vitro. Effects of cisplatin (IV) and HA-Pt (SC) in rodents were tested by clinicopathologic assays. In the clinical trial, dogs with cancer received 1 to 4 injections of HA-Pt (10 to 30 mg/m2, intratumoral or peritumoral, q 3 wk). Blood samples were collected for pharmacokinetic analysis; CBC, serum BUN and creatinine concentration measurement, and urinalysis were conducted before and 1 week after each treatment. Some dogs underwent hepatic enzyme testing. Tumors were measured before the first treatment and 3 weeks after each treatment to assess response.
RESULTS No adverse drug effects were detected in pretrial assessments in rodents. Seven of 16 dogs completed the study; 3 had complete tumor responses, 3 had stable disease, and 1 had progressive disease. Three of 7 dogs with oral and nasal squamous cell carcinoma (SCC) that completed the study had complete responses. Myelosuppression and cardiotoxicosis were identified in 6 and 2 dogs, respectively; none had nephrotoxicosis. Four of 5 dogs with hepatic enzymes assessed had increased ALT activities, attributed to diaquated cisplatin products in the HA-Pt. Pharmacokinetic data fit a 3-compartment model.
CONCLUSIONS AND CLINICAL RELEVANCE HA-Pt treatment resulted in positive tumor responses in some dogs, primarily those with SCC. The adverse effect rate was high.
IMPACT FOR HUMAN MEDICINE Oral SCC in dogs has characteristics similar to human head and neck SCC; these results could be useful in developing human treatments.
Objective—To evaluate safety and efficacy of LDI-100, a preparation containing human chorionic gonadotropin (hCG) and bacillus Calmette-Guerin (BCG), in the treatment of dogs with mast cell tumors and to compare results with those from a control group receiving single-agent vinblastine.
Animals—95 dogs with measurable grade II or III mast cell tumors.
Procedures—Dogs were randomized to receive either LDI-100 (1.35 ng of BCG and 2 units of hCG, SC, q 24 h) or vinblastine (2 mg/m2, IV, q 1 wk) for 6 weeks. Tumors were measured at baseline and day 42, and dogs were monitored for signs of toxicosis. Clinical performance scores were recorded at each visit. Differences in host factors (sex, weight, and age), clinical performance score, tumor response, and adverse events were analyzed.
Results—46 dogs received LDI-100, and 49 dogs received vinblastine. No significant differences were found between the 2 treatment groups with regard to host factors or clinical performance score. Tumor response (≥50% reduction) rates were similar between the LDI-100 and vinblastine group (28.6% and 11.7%, respectively). Dogs in the LDI-100 group had significantly less neutropenia than the vinblastine group.
Conclusions and Clinical Relevance—hCG and BCG have immunomodulatory and antitumor effects against a variety of malignancies in humans and dogs. In this study, LDI-100 provided clinical responses comparable to single-agent vinblastine chemotherapy but without myelosuppression. LDI-100 is a promising new agent that should be further investigated for multimodality therapy of mast cell tumors in dogs.
Objective—To evaluate the veterinary version of the
bladder tumor antigen (V-BTA) test as a screening test
for transitional cell carcinoma (TCC) of the lower urinary
tract of dogs.
Animals—229 client-owned dogs.
Procedure—Urine samples from dogs were shipped
overnight to a single laboratory to facilitate testing
within 48 hours of collection by use of the V-BTA rapid
latex agglutination urine dipstick test. Groups of dogs
included the following: 1) dogs with TCC of the lower
urinary tract, 2) healthy control dogs, 3) unhealthy
control dogs with non-TCC urinary tract disease, and
4) unhealthy control dogs without urinary tract disease.
Test sensitivity and specificity were calculated
by use of standard methods. Logistic models were
developed to assess the effect of disease status, test
conditions, urine composition, and signalment on the
performance of the V-BTA test.
Results—A total of 229 urine samples were analyzed,
including 48 from dogs with suspected (n = 3) or confirmed
(45) TCC. Test sensitivities were 88, 87, and
85% for all dogs with (suspected and confirmed) TCC,
dogs with confirmed TCC at any site, and dogs with
confirmed TCC of the urinary bladder, respectively.
Test specificities were 84, 41, and 86% for healthy
control dogs, unhealthy control dogs with non-TCC
urinary tract disease, and unhealthy control dogs
without urinary tract disease, respectively. The test
performed slightly better on centrifuged urine samples
than on uncentrifuged urine samples.
Conclusions and Clinical Relevance—Our results
indicate that the V-BTA test is useful in screening for
urinary tract TCC in dogs. (Am J Vet Res
Objective—To determine the prognostic factors for
survival and tumor recurrence in dogs with cutaneous
mast cell tumors (MCTs) in the perineal and inguinal
regions treated surgically with or without adjunctive
radiation therapy, chemotherapy, or both.
Procedure—Medical records of dogs with histologically
confirmed MCTs in the perineal region, inguinal
region, or both treated surgically with or without
adjunctive radiation therapy, chemotherapy, or both
Results—Mean tumor-free interval was 1,635 days
(median not reached), and 1- and 2-year tumor-free
rates were 79% and 71%, respectively. Median survival
time was 1,111 days (mean, 1,223 days), and 1-
and 2-year survival rates were 79% and 61%, respectively.
Factors that negatively influenced survival time
were age at diagnosis, tumor recurrence, and treatment
Conclusions and Clinical Relevance—Results indicated
that dogs with MCTs in the inguinal and perineal
regions, if appropriately treated, may have survival
times and tumor-free intervals similar to dogs
with MCTs in other locations. ( J Am Vet Med Assoc