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Mast Cell Tumors (mast + cell_tumor)
Selected AbstractsEfficacy of Vinblastine for Treatment of Canine Mast Cell TumorsJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 6 2008K.M. Rassnick Background: The optimal dosage and clinical efficacy of vinblastine (VBL) for treatment of mast cell tumors (MCTs) in dogs has not been established. Hypothesis: Single-agent VBL has antitumor activity against MCTs in dogs. Animals: Fifty-one dogs with nonresectable grade II or III cutaneous MCTs. Methods: Prospective, open clinical trial. Dogs were systematically allocated (by hospital record number) to receive IV treatment with VBL at a dosage of 2.0 mg/m2 (weekly for 4 treatments then biweekly for 4 treatments; VBL 2.0) or treatment with VBL at a dosage of 3.5 mg/m2 (biweekly for 5 treatments; VBL 3.5). The primary outcome measure was reduction in tumor size. Results: Twenty-five dogs were allocated to the VBL 2.0 group and 26 were allocated to the VBL 3.5 group. In the VBL 2.0 group, 3 (12%) had a partial response (PR) for a median of 77 days (range, 48,229 days). Overall response rate in the VBL 3.5 group was 27%. One dog (4%) had a complete response for 63 days and 6 dogs (23%) had a PR for a median of 28 days (range, 28,78 days). Toxicoses were uncommon in the VBL 2.0 group. Twelve (46%) dogs in the VBL 3.5 group had <500 neutrophils/,L 7 days after treatment; 2 dogs with neutropenia developed concurrent fevers. Conclusions and Clinical Importance: VBL, when used as a single-agent, has activity against MCTs in dogs although the response rate is lower than those reported for VBL-containing combination protocols. Further, findings suggest VBL at a dosage of 3.5 mg/m2 should be considered for use in future phase II/III trials. [source] A Phase II Clinical Trial of Vinorelbine in Dogs with Cutaneous Mast Cell TumorsJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 2 2008I.A. Grant Background: Few effective drugs are available to treat dogs with locally aggressive or metastatic mast cell disease. Hypothesis: Vinorelbine, a semisynthetic derivative of vinblastine, is an effective drug for the treatment of canine mast cell tumors (MCT). Animals: Twenty-four dogs with cutaneous MCT. Methods: Dogs with at least 1 measurable, cytologically confirmed, and previously untreated cutaneous MCT received a single treatment with vinorelbine at the previously established dosage of 15 mg/m2 IV. Tumor measurements and CBC were evaluated before and 7 days after treatment. Adverse events were graded according to Veterinary Cooperative Oncology Group (VCOG) guidelines. Statistics: Data were accrued in accordance with a Simon's 2-stage design with a noninteresting response rate of .05, a target response of .25, and , and , values of .10. Results: Three of 24 dogs (13%) had a response to treatment, including 1 measurable complete response and 1 measurable partial response. The 3rd dog had microscopic complete response to treatment with stable measurable disease. Twenty other dogs (83%) had stable disease and 1 dog (4%) had progressive disease. Neutropenia occurred in 13 dogs (54%) (grade 1, n = 4; grade 3, n = 6; grade 4, n = 3). Gastrointestinal toxicity occurred in 11 dogs (46%) (anorexia: grade 1, n = 3; grade 2, n = 1; grade 3, n = 1; diarrhea: grade 1, n = 2; grade 3, n = 1; vomiting: grade 1, n = 5; grade 3, n = 1). Conclusions and Clinical Importance: Vinorelbine was associated with an overall response rate of 13% and a high prevalence of neutropenia. Additional studies are indicated to determine if repeated dosing of vinorelbine or combination of vinorelbine with other drugs increases the observed biologic activity against canine MCT. [source] Association between Waste Management and Cancer in Companion AnimalsJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 3 2009L. Marconato Background: Increased cancer rates have been documented in people residing in areas around Naples characterized by illegal dumping and incineration of waste. Hypothesis: Risk of cancer in dogs and cats is associated with waste management. Animals: Four hundred and fifty-three dogs and cats with cancer and 1,554 cancer-free animals. Methods: Hospital-based case-control study in Naples (low danger) and nearby cities having a history of illegal waste dumping (high danger). Odds ratio (OR) between high- and low-danger areas was calculated for all tumors and various malignancies in dogs and cats. Results: An increased risk for cancer development was identified in dogs but not in cats residing in high-danger areas (OR: 1.55; 95% confidence interval: 1.18,2.03; P < .01). A 2.39-fold increased risk of lymphoma (P < .01) accounted for the greater tumor frequency in dogs residing in high-danger areas. The risk of mast cell tumor and mammary cancer did not differ in dogs residing in high- or low-danger areas. Conclusions and Clinical Importance: Waste emission from illegal dumping sites increases cancer risk in dogs residing in high-danger areas. An increased prevalence of lymphoma has been previously recognized in humans living close to illegal waste dumps. Thus, epidemiological studies of spontaneous tumors in dogs might suggest a role for environmental factors in canine and human carcinogenesis and can predict health hazards for humans. [source] Efficacy of Vinblastine for Treatment of Canine Mast Cell TumorsJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 6 2008K.M. Rassnick Background: The optimal dosage and clinical efficacy of vinblastine (VBL) for treatment of mast cell tumors (MCTs) in dogs has not been established. Hypothesis: Single-agent VBL has antitumor activity against MCTs in dogs. Animals: Fifty-one dogs with nonresectable grade II or III cutaneous MCTs. Methods: Prospective, open clinical trial. Dogs were systematically allocated (by hospital record number) to receive IV treatment with VBL at a dosage of 2.0 mg/m2 (weekly for 4 treatments then biweekly for 4 treatments; VBL 2.0) or treatment with VBL at a dosage of 3.5 mg/m2 (biweekly for 5 treatments; VBL 3.5). The primary outcome measure was reduction in tumor size. Results: Twenty-five dogs were allocated to the VBL 2.0 group and 26 were allocated to the VBL 3.5 group. In the VBL 2.0 group, 3 (12%) had a partial response (PR) for a median of 77 days (range, 48,229 days). Overall response rate in the VBL 3.5 group was 27%. One dog (4%) had a complete response for 63 days and 6 dogs (23%) had a PR for a median of 28 days (range, 28,78 days). Toxicoses were uncommon in the VBL 2.0 group. Twelve (46%) dogs in the VBL 3.5 group had <500 neutrophils/,L 7 days after treatment; 2 dogs with neutropenia developed concurrent fevers. Conclusions and Clinical Importance: VBL, when used as a single-agent, has activity against MCTs in dogs although the response rate is lower than those reported for VBL-containing combination protocols. Further, findings suggest VBL at a dosage of 3.5 mg/m2 should be considered for use in future phase II/III trials. [source] Phase I Dose Escalation of Single-Agent Vinblastine in DogsJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 6 2008D.B. Bailey Background: Vinblastine (VBL) is commonly used in dogs at a dosage of 2.0 mg/m2. The minimal toxicity observed at this dosage indicates that higher dosages might be well tolerated. Hypothesis: The maximum tolerated dosage (MTD) for a single VBL treatment is higher than the previously published dosage of 2.0 mg/m2. Animals: Twenty-three dogs with lymphoma or cutaneous mast cell tumors. Methods: Dogs received 1 single-agent VBL treatment IV. The starting dosage was 3.0 mg/m2, and dosages were increased in increments of 0.5 mg/m2 in cohorts of 3 dogs. Hematologic toxicity was assessed with weekly CBCs. Gastrointestinal toxicity was assessed from medical histories from owners. Once the MTD was determined, additional dogs were treated with VBL at that dosage. Dogs whose cancers responded to VBL continued to receive treatments q2,3 weeks. Results: VBL dosages ranged from 3.0 to 4.0 mg/m2. Neutropenia was the dose-limiting toxicity, with the nadir identified 7 days after treatment and resolving by 14 days after treatment. The MTD was 3.5 mg/m2. Sixteen dogs were treated at this dosage, and 3 experienced severe toxicity characterized by asymptomatic grade 4 neutropenia, febrile grade 4 neutropenia, and death. Gastrointestinal toxicity was mild and self-limiting. Preliminary evidence of antitumor activity was identified in 2 of 12 dogs with lymphoma treated at the MTD. Conclusions and Clinical Importance: In dogs, single-agent VBL is well tolerated at a dosage of 3.5 mg/m2 IV. At this dosage, the minimum safe treatment interval is q2 weeks, and adjunct treatment with prophylactic antibiotics should be considered. [source] A Phase II Clinical Trial of Vinorelbine in Dogs with Cutaneous Mast Cell TumorsJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 2 2008I.A. Grant Background: Few effective drugs are available to treat dogs with locally aggressive or metastatic mast cell disease. Hypothesis: Vinorelbine, a semisynthetic derivative of vinblastine, is an effective drug for the treatment of canine mast cell tumors (MCT). Animals: Twenty-four dogs with cutaneous MCT. Methods: Dogs with at least 1 measurable, cytologically confirmed, and previously untreated cutaneous MCT received a single treatment with vinorelbine at the previously established dosage of 15 mg/m2 IV. Tumor measurements and CBC were evaluated before and 7 days after treatment. Adverse events were graded according to Veterinary Cooperative Oncology Group (VCOG) guidelines. Statistics: Data were accrued in accordance with a Simon's 2-stage design with a noninteresting response rate of .05, a target response of .25, and , and , values of .10. Results: Three of 24 dogs (13%) had a response to treatment, including 1 measurable complete response and 1 measurable partial response. The 3rd dog had microscopic complete response to treatment with stable measurable disease. Twenty other dogs (83%) had stable disease and 1 dog (4%) had progressive disease. Neutropenia occurred in 13 dogs (54%) (grade 1, n = 4; grade 3, n = 6; grade 4, n = 3). Gastrointestinal toxicity occurred in 11 dogs (46%) (anorexia: grade 1, n = 3; grade 2, n = 1; grade 3, n = 1; diarrhea: grade 1, n = 2; grade 3, n = 1; vomiting: grade 1, n = 5; grade 3, n = 1). Conclusions and Clinical Importance: Vinorelbine was associated with an overall response rate of 13% and a high prevalence of neutropenia. Additional studies are indicated to determine if repeated dosing of vinorelbine or combination of vinorelbine with other drugs increases the observed biologic activity against canine MCT. [source] Alterations of the c-kit gene in testicular germ cell tumorsCANCER SCIENCE, Issue 6 2003Yuji Sakuma Expression and gain-of-function mutation of the c-kit gene, that encodes a receptor tyrosine kinase (KIT), have been reported in mast cell tumors and gastrointestinal stromal tumors (GISTs). Among human testicular germ cell tumors (GCTs), seminomas and seminoma components of mixed GCTs have also been shown to express KIT, but only one study has found the c-kit gene mutation at exon 17 in seminoma. To elucidate the frequency and location of the c-kit gene mutation of testicular GCTs, we analyzed the whole coding region of the c-kit complementary DNA along with 4 mutational hot spots (exons 9, 11, 13 and 17) of the c-kit genomic DNA by polymerase chain reaction and direct sequencing. Somatic mutations were found in 4 pure seminomas of 34 testicular GCTs (11.8%). One mutation was found in exon 11 (W557R) and the others were observed in exon 17 (D816H and D816V). These types of mutations were reported in GISTs (W557R), seminoma (D816H) and mastocytosis (D816V) and were considered to be gain-of-function mutations, although there were no differences of any clinicopathological factors or outcome between patients with and without mutations. Additionally, we also demonstrated coexpression of Gly-Asn-Asn-Lys510,513 (GNNK)+ and GNNK- isoforms of the c-kit gene with dominance of the GNNK- transcript in all testicular GCTs. The mutations and/or preferential expression of GNNK- isoform of the c-kit gene might play an important role in the development of testicular GCTs, and these tumors may also be targets for STI571, which is a promising drug for advanced and metastatic GISTs. [source] | ||||||||||