RESUMO
BACKGROUND: Nonresectable mast cell tumors (MCT) in dogs remain a therapeutic challenge, and investigation of novel combination therapies is warranted. Intermittent administration of tyrosine kinase inhibitors (TKI) combined with cytotoxic chemotherapy may effectively chemosensitize canine MCT while decreasing cost and adverse effects associated with either agent administered as monotherapy. HYPOTHESIS/OBJECTIVES: The primary study objectives were to (1) identify the maximally tolerated dose (MTD), (2) determine the objective response rate (ORR) and (3) describe the adverse event profile of pulse-administered toceranib phosphate (TOC) combined with lomustine. ANIMALS: Forty-seven client-owned dogs with measurable MCT. METHODS: Toceranib phosphate was given PO on days 1, 3 and 5 of a 21-day cycle at a target dosage of 2.75 mg/kg. Lomustine was given PO on day 3 of each cycle at a starting dosage of 50 mg/m(2) . All dogs were concurrently treated with diphenhydramine, omeprazole, and prednisone. RESULTS: The MTD of lomustine was established at 50 mg/m(2) when combined with pulse-administered TOC; the dose-limiting toxicity was neutropenia. Forty-one dogs treated at the MTD were evaluable for outcome assessment. The ORR was 46% (4 complete response, 15 partial response) and the overall median progression-free survival (PFS) was 53 days (1 to >752 days). On multivariate analysis, variables significantly associated with improved PFS included response to treatment, absence of metastasis, and no previous chemotherapy. CONCLUSIONS AND CLINICAL IMPORTANCE: Combined treatment with pulse-administered TOC and lomustine generally is well tolerated and may be a reasonable treatment option for dogs with unresectable or metastatic MCT.
Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Doenças do Cão/tratamento farmacológico , Indóis/uso terapêutico , Lomustina/uso terapêutico , Mastocitose/veterinária , Proteínas Tirosina Quinases/antagonistas & inibidores , Pirróis/uso terapêutico , Animais , Antineoplásicos Alquilantes/administração & dosagem , Doenças do Cão/genética , Cães , Esquema de Medicação/veterinária , Quimioterapia Combinada , Feminino , Indóis/administração & dosagem , Lomustina/administração & dosagem , Masculino , Mastocitose/tratamento farmacológico , Mastocitose/genética , Reação em Cadeia da Polimerase/veterinária , Proteínas Proto-Oncogênicas c-kit/genética , Pirróis/administração & dosagemRESUMO
BACKGROUND: Canine cutaneous T-cell lymphoma (CTCL) is an uncommon disease for which efficacious therapies are lacking. The novel anticancer nucleotide prodrug VDC-1101 (formerly known as GS-9219) has shown efficacy in dogs with multicentric lymphoma. One of the observed adverse effects with this drug was a skin change characterized by hair loss, erythema, and pruritus, implying delivery of VDC-1101 to the skin. HYPOTHESIS/OBJECTIVES: The primary study objective was to identify the objective response rate (ORR) to VDC-1101 in canine CTCL; secondary objectives included characterization of progression-free survival (PFS) and adverse events (AEs). ANIMALS: Twelve dogs with chemotherapy-naïve or relapsed, histologically and immunohistochemically confirmed CTCL. METHODS: Dogs received VDC-1101 as a 30-minute IV infusion once every 21 days. Prednisone (1 mg/kg PO q48h) was administered concurrently. RESULTS: In 11 evaluable patients, responses included 1 complete response (CR), 4 partial responses (PR), 2 stable disease (SD), and 4 progressive disease for an ORR of 45% and biologic response rate (CR/PR/SD) of 64%. The median PFS was 37.5 days (26 to >399 days), which includes 1 durable and ongoing CR (>1 year). Gastrointestinal and hematologic AEs were mild; no dogs developed grade 3 or 4 AEs. Three dogs developed dermatopathies and 1 of these dogs was removed from the study as a result of this AE. CONCLUSIONS AND CLINICAL IMPORTANCE: VDC-1101 has activity against canine CTCL and could provide another treatment option in a disease process with a poor prognosis.
Assuntos
Alanina/análogos & derivados , Antineoplásicos/uso terapêutico , Doenças do Cão/tratamento farmacológico , Linfoma Cutâneo de Células T/veterinária , Purinas/uso terapêutico , Neoplasias Cutâneas/veterinária , Alanina/efeitos adversos , Alanina/uso terapêutico , Animais , Antineoplásicos/efeitos adversos , Cães , Feminino , Linfoma Cutâneo de Células T/tratamento farmacológico , Masculino , Purinas/efeitos adversos , Dermatopatias/induzido quimicamente , Dermatopatias/veterinária , Neoplasias Cutâneas/tratamento farmacológico , Resultado do TratamentoRESUMO
BACKGROUND: Many chemotherapy protocols have been reported for treatment of canine appendicular osteosarcoma (OSA), but outcome comparisons in a single population are lacking. OBJECTIVE: To evaluate the effects of protocol and dose intensity (DI) on treatment outcomes for carboplatin and doxorubicin-based chemotherapy protocols. ANIMALS: Four hundred and seventy dogs with appendicular OSA. METHODS: A retrospective cohort study was performed comprising consecutive dogs treated (1997-2012) with amputation followed by 1 of 5 chemotherapy protocols: carboplatin 300 mg/m(2) IV q21d for 4 or 6 cycles (CARBO6), doxorubicin 30 mg/m(2) IV q14d or q21d for 5 cycles, and alternating carboplatin 300 mg/m(2) IV and doxorubicin 30 mg/m(2) IV q21d for 3 cycles. Adverse events (AE) and DI were evaluated. Kaplan-Meier survival curves and Cox proportional hazards regression were used to compare disease-free interval (DFI) and survival time (ST) among protocols. RESULTS: The overall median DFI and ST were 291 days and 284 days, respectively. A lower proportion of dogs prescribed CARBO6 experienced AEs compared to other protocols (48.4% versus 60.8-75.8%; P = .001). DI was not associated with development of metastases or death. After adjustment for baseline characteristics and prognostic factors, none of the protocols provided a significant reduction in risk of development of metastases or death. CONCLUSIONS AND CLINICAL IMPORTANCE: Although choice of protocol did not result in significant differences in DFI or ST, the CARBO6 protocol resulted in a lower proportion of dogs experiencing AEs, which could be advantageous in maintaining high quality of life during treatment. DI was not a prognostic indicator in this study.
Assuntos
Neoplasias Ósseas/veterinária , Carboplatina/uso terapêutico , Doenças do Cão/tratamento farmacológico , Doxorrubicina/uso terapêutico , Osteossarcoma/veterinária , Amputação Cirúrgica/veterinária , Animais , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/cirurgia , Carboplatina/administração & dosagem , Doenças do Cão/cirurgia , Cães , Doxorrubicina/administração & dosagem , Esquema de Medicação , Extremidades/cirurgia , Feminino , Masculino , Osteossarcoma/tratamento farmacológico , Osteossarcoma/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
The basic child-health problems in the shanty towns of Lima are protein-calorie malnutrition and infectious disease. The background of social, economic and cultural conditionsa are related to these main health problems. The basic problems are poverty, lack of sewage disposal and running water, and the maldistribution of public expenditure between city and countryside on one hand and curative and preventive medicine on the other. Despite official statistics, which show a steadily decreasing infant mortality rate in Peru, and all other Latin American countries, it seems that the Infant Mortality Rate is almost twice the official states rate. Health education, particularly in nutritional matters, is not adapted to indigenous foods and customs, but attempts to promote westernized conceptrs. Medical care in Peru is by large directed to the needs of the middle class, and the middle class by and large dictates the type of medical care available.