Assessment of anemia as an independent predictor of response to chemotherapy and survival in dogs with lymphoma: 96 cases (1993-2006)

OBJECTIVE: To determine whether the presence of anemia (Hct < or = 37%) at the time of diagnosis of lymphoma is a negative prognostic indicator for response to treatment and survival time in dogs that are undergoing chemotherapy. DESIGN: Retrospective case series. Animals-96 dogs with lymphoma that were receiving chemotherapy. Procedures-Information regarding signalment, initial hematologic data, chemotherapy protocol, clinical response, and date of death was retrospectively collected from medical records of dogs with lymphoma. Univariate, multivariate, and survival analyses were performed to determine the effect of anemia on initial response to chemotherapy and on survival time. RESULTS: Overall, dogs without anemia (n = 56) were 4 times as likely as dogs with anemia (40) to have a complete response following chemotherapy. Anemic dogs had a significantly shorter median survival time (139 days), compared with survival time of nonanemic dogs (315 days). Subset analysis of dogs with multicentric lymphoma (matched for clinical stage and chemotherapy protocol) revealed that the dogs with anemia (n = 24) had a significantly shorter median survival time (101 days), compared with survival time of dogs without anemia (24; 284 days). Other variables were not associated with survival time. CONCLUSIONS AND CLINICAL RELEVANCE: These findings suggested that anemia is a negative prognostic factor for dogs with lymphoma that are undergoing chemotherapy. Further investigation will be necessary to determine the impact of resolution of anemia on clinical outcome in dogs with lymphoma.     

Laser lithotripsy for treatment of canine uroliths

OBJECTIVE: To confirm in vivo optimal laser energy settings previously determined in vitro for lithotripsy, to develop a technique for Ho:YAG laser lithotripsy, and to evaluate acute and chronic tissue effects of laser lithotripsy. STUDY DESIGN: Prospective, randomized preclinical trial. ANIMALS OR SAMPLE POPULATION: Nineteen intact, adult male dogs. METHODS: Via cystotomy, a single urolith was inserted into the urethra to the level of the base of the os penis to simulate obstruction. Uroliths (calcium oxalate, urate, or magnesium ammonium phosphate) were fragmented by Ho:YAG laser, in contact mode through a 320 micro optic fiber, passed through the operating channel of a 2.8 mm flexible endoscope. The time and total energy to fragmentation were recorded. Dogs were euthanatized immediately after lithotripsy (3 dogs) or at 3 days (7 dogs), and urethral lesions and any stone remnants were evaluated. Urethral integrity was also evaluated in 9 other dogs by endoscopy on day 10; these were also monitored clinically for 30 days. RESULTS: The mean time for adequate fragmentation was 166.7 seconds (range, 47-494.5 seconds). The mean+/-SD energy used was 1418+/-851.2 J. In part 1, 2 dogs were obstructed with urolith fragments at necropsy. Eight dogs had minimal (<30 mg) or no urolith material evident within the urethra. Four dogs had gross focal or circumferential erosion, ulceration, or hemorrhage of the urethral mucosa. Lesions were not associated with the site of laser irradiation in 2 dogs. In dogs observed for 30 days, hematuria, pollakiuria, and stranguria that were observed after lithotripsy, resolved in all affected dogs by day 5. No mucosal lesions were observed by endoscopy and none of the dogs became obstructed. CONCLUSION: Laser lithotripsy with the Ho:YAG laser in contact mode successfully fragmented obstructive uroliths in male dogs. CLINICAL RELEVANCE: Laser lithotripsy may be a clinically relevant technique for treatment of urolithiasis in male dogs; clinical studies to evaluate long-term effects on urethral mucosa and the role of repeat treatment for recurrence are indicated.     

Preclinical evaluation of 5-aminolevulinic acid-based photodynamic therapy for canine transitional cell carcinoma

As a prelude to photodynamic therapy, 5‐aminolevulinic acid (ALA) was given orally to healthy dogs. ALA‐induced protoporphyrin IX (PpIX) fluorescence significantly increased in the mucosa of the urinary bladder in an ALA dose‐dependent fashion. Vomiting occurred after ALA administration in 70% of the dogs but did not affect PpIX fluorescence. ALA‐based photodynamic therapy (PDT) of the urinary bladder in healthy dogs caused only submucosal oedema within the bladder wall. No haematologic or serum biochemistry abnormalities were observed after ALA administration. Microscopic haematuria was observed in all the dogs after PDT but was mild and self limiting. ALA‐based PDT was administered to six dogs with transitional cell carcinoma (TCC) of the lower urinary tract. ALA‐based PDT resulted in tumour progression‐free intervals from 4 to 34 weeks in five dogs; one dog with pre‐existing hydronephrosis died shortly after PDT. Dogs with TCC represent an outbred, spontaneous, tumour model for developing PDT protocols for humans with bladder cancer.     

Phase I clinical trial of the use of zinc phthalocyanine tetrasulfonate as a photosensitizer for photodynamic therapy in dogs

OBJECTIVE: To determine the threshold for acute toxicosis of parenterally administered zinc phthalocyanine tetrasulfonate (ZnPcS(4)), a candidate second-generation photosensitizer, in mice and evaluate the compound's safety in a phase I clinical trial of ZnPcS(4)-based photodynamic therapy (PDT) in pet dogs with naturally occurring tumors. ANIMALS: Male Swiss-Webster mice and client-owned dogs with naturally occurring neoplasms. PROCEDURES: For the study of acute toxicosis, mice were given graded doses of ZnPcS(4). To determine safety, a rapid-titration phase I clinical trial of ZnPcS(4)-based PDT in tumor-bearing dogs was conducted. RESULTS: In mice, administration of >or= 100 mg of ZnPcS(4)/kg resulted in renal tubular necrosis 24 hours after IP injection. In tumor-bearing dogs, ZnPcS(4) doses 相似文献   

Phase II clinical trial of combination chemotherapy with dexamethasone for lymphoma in dogs

Dogs with histologically confirmed lymphoma were treated with a 14-week induction chemotherapy protocol that included dexamethasone. A phase II clinical trial was done using a standard two-stage design. Complete remission occurred in 21 (88%) dogs, with a median initial progression-free interval of 186 days. Toxicity was mild and self-limiting in the majority of dogs.     

Evaluation of cisplatin administered with piroxicam in dogs with transitional cell carcinoma of the urinary bladder

OBJECTIVE: To evaluate the antitumor activity and toxic effects of a conservative dose of cisplatin administered in combination with piroxicam to dogs with transitional cell carcinoma (TCC) of the urinary bladder. DESIGN: Clinical trial (nonrandomized, noncontrolled). ANIMALS: 14 client-owned dogs with histologically confirmed TCC of the urinary bladder. PROCEDURES: Each dog was treated with cisplatin (50 mg/m(2), i.v., q 21 d [reduced to 40 mg/m(2), i.v., q 21 d because of toxic effects]) and piroxicam (0.3 mg/kg [0.14 mg/lb], PO, q 24 h). A CBC, serum biochemical analyses, and urinalysis were performed prior to each cisplatin treatment. Tumor staging (determined from thoracic and abdominal radiographic and urinary bladder ultrasonographic findings) was performed before treatment and at 6-week intervals during treatment. RESULTS: 5 dogs received only 1 dose of cisplatin because of the rapid progression of disease (n = 2) or toxic effects (3). With regard to the neoplastic disease among the other 9 dogs, 1 had partial remission, 5 had stable disease, and 3 had progressive disease after 6 weeks of treatment. Median progression-free interval was 78 days (range, 20 to 112 days). Median survival time was 307 days (range, 29 to 929 days). Moderate to severe renal toxicosis and moderate to severe gastrointestinal toxicosis developed in 5 and 8 dogs, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Because of minimal efficacy and associated renal and gastrointestinal toxicosis, administration of cisplatin (40 to 50 mg/m(2)) with piroxicam cannot be recommended for treatment of dogs with TCC of the urinary bladder.     

A Candidate Second‐Generation Photosensitizer for Photodynamic Therapy in Veterinary Medicine

Introduction:  Photodynamic therapy (PDT) involves the light activation of a drug within a tumor causing selective tumor cell death. Unfortunately, some photosensitizing drugs have been associated with adverse reactions in veterinary patients. Zinc phthalocyanine tetrasulfonate (ZnPcS4) is a promising second‐generation photosensitizer for use in veterinary medicine, however, it cannot be applied clinically until safety and efficacy data are available.
Methods:  Increasing intraperitoneal doses of ZnPcS4 were given to Swiss Webster mice to assess acute toxicity. Based on mouse toxicity data, a phase I clinical trial of ZnPcS4‐based PDT in tumor‐bearing dogs was designed, using an accelerated titration scheme starting at 0.5% of the minimum toxic dose in mice. 24‐hours after ZnPcS4 administration tumors were irradiated with 675 nm light and dogs were evaluated by routine hematology and serum biochemistry at regular intervals after PDT.
Results:  Doses >125 mg/kg were associated with acute toxicity and mortality in Swiss Webster mice, suggesting the minimum toxic dose is 120–125 mg/kg. One dog, a Golden retriever with a massive malignant fibrous histiocytoma, has been entered into the phase I clinical trial. No deleterious effects were noted after ZnPcS4 administration. Within 48 hours of PDT, the tumor was dark and necrotic, with no grossly visible changes to the surrounding normal tissues. Histological examination of the PDT‐treated tumor confirmed widespread necrosis and thrombosis consistent with PDT‐mediated damage. The owner reported no adverse effects after treatment.
Conclusions:  Although preliminary data are encouraging, additional evaluation of ZnPcS4‐based PDT is required to determine its role in veterinary medicine.     

Histologic comparison of skin biopsy specimens collected by use of carbon dioxide or 810-nm diode lasers from dogs

OBJECTIVE: To compare histologic artifacts caused by carbon dioxide (CO2) or 810-nm diode surgical lasers used to obtain small biopsy specimens of skin from healthy dogs. DESIGN: Prospective study. ANIMALS: 4 dogs. PROCEDURE: 21 skin biopsy specimens were collected from each dog. Three biopsy specimens were obtained with a CO2 or an 810-nm diode laser at 3 operating settings each, and 3 biopsy specimens were obtained with a 6-mm biopsy punch instrument (controls). After processing, biopsy specimens were examined for artifacts related to laser-tissue interactions. Microscopically visible char was measured from the lateral edge of each specimen obtained with a laser. RESULTS: There were no significant differences among mean char distances in biopsy specimens obtained with the CO2 laser at various settings. Mean char distance was significantly greater in all skin biopsy specimens obtained with the diode laser, compared with those obtained with the CO2 laser. Mean char distance was significantly greater in biopsy specimens obtained with the 810-nm diode laser at high power, compared with biopsy specimens obtained with the 810-nm diode laser at low power. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that the CO2 laser caused less thermal injury at margins of skin biopsy specimens; therefore, if a surgical laser is used for removal of cutaneous masses or to obtain skin biopsy specimens, use of the CO2 laser is recommended. Veterinarians performing a biopsy by using a surgical laser should be aware that laser-induced artifacts may render small biopsy specimens useless for providing accurate histologic diagnosis.