RESUMEN
Cyclophosphamide is an alkylating agent used to treat cats with lymphoma, carcinomas and sarcomas. However, no clear consensus exists regarding the maximum tolerated dose (MTD) of oral cyclophosphamide in cats. Toxicities are rarely reported at published oral dosages of cyclophosphamide (200-300 mg/m2). The primary aim of this prospective study was to determine the MTD of oral cyclophosphamide in tumour-bearing cats via a modified phase I trial. A secondary aim was to define any toxicity. Forty-six client-owned tumour-bearing cats were enrolled. The cyclophosphamide dosage was escalated by approximately 10% (300, 330, 360, 400, 440, 460 and 480 mg/m2) in cohorts of at least six cats. The MTD of oral cyclophosphamide in this study was 460 mg/m2 with an inter-treatment interval of two to three weeks. Haematology is recommended 7 and 14 days after first cyclophosphamide treatment, and immediately before each subsequent dosage of cyclophosphamide or any potentially myelosuppressive chemotherapy agent. The dose-limiting toxicity was neutropenia with nadir at 7-21 days. This higher dosage was considered safe in combination with prednisolone and L-asparaginase. However, the higher dose of oral cyclophosphamide has not been evaluated in combination with other chemotherapy agents and thus should not be administered with these agents.
Asunto(s)
Antineoplásicos Alquilantes/administración & dosificación , Enfermedades de los Gatos/tratamiento farmacológico , Ciclofosfamida/administración & dosificación , Dosis Máxima Tolerada , Neoplasias/veterinaria , Administración Oral , Animales , Antineoplásicos Alquilantes/toxicidad , Gatos , Ciclofosfamida/toxicidad , Neoplasias/tratamiento farmacológico , Estudios ProspectivosRESUMEN
Cyclophosphamide is an alkylating agent used as chemotherapy for cats with lymphoma, carcinomas and sarcomas. Clinical and pharmacokinetic studies of cyclophosphamide in normal and tumor-bearing cats have shown minimal toxicity and cyclophosphamide at clinically used dosages rarely requires dosage adjustment or treatment delays. Dose intensity appears important for treatment of most cancers; the aim of this study was to perform a modified dose escalation study of cyclophosphamide to establish the maximally tolerated dosage (MTD) for intravenous cyclophosphamide in cats. The dose limiting toxicity appeared to be neutropenia, and 30% of cats experienced grade 3 or grade 4 neutropenia at a cyclophosphamide dosage of 480mg/m2, which was determined as the MTD. Delayed neutropenia was observed commonly at higher dosages. Thrombocytopenia was less common than neutropenia, and always transient. Gastrointestinal toxicities were uncommon even at MTD. The recommended dosage for single agent cyclophosphamide in cats is 460mg/m2 with a post-treatment interval of three weeks, with hematology performed before any subsequent chemotherapy is administered. This dosage appears safe in combination with prednisolone and l-asparaginase; but has not been evaluated in combination with other chemotherapy agents, or with a post-treatment interval shorter than 3 weeks. Such combinations and shorter intervals are found in some protocols, so this recommended cyclophosphamide dose cannot be considered a direct substitute for cyclophosphamide dosages in existing protocols. There is a suggestion that inadequate renal function may exacerbate the myelosuppression of cyclophosphamide which should be further evaluated.
Asunto(s)
Antineoplásicos Alquilantes/administración & dosificación , Enfermedades de los Gatos/tratamiento farmacológico , Ciclofosfamida/administración & dosificación , Animales , Antineoplásicos Alquilantes/efectos adversos , Gatos , Ciclofosfamida/efectos adversos , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Infusiones Intravenosas/veterinaria , Linfoma/tratamiento farmacológico , Linfoma/veterinaria , Masculino , Neoplasias Mamarias Animales/tratamiento farmacológico , Neutropenia/inducido químicamente , Neutropenia/veterinaria , Sarcoma/tratamiento farmacológico , Sarcoma/veterinaria , Resultado del TratamientoRESUMEN
BACKGROUND: Histiocytic sarcomas (HS) frequently metastasise, most commonly to visceral sites, but also to regional lymph nodes. Nodal metastases are associated with a poorer prognosis. This retrospective study aimed to evaluate prognostic factors, including the effect of adjuvant chemotherapy, on survival in dogs with nodal, but not systemic, metastases from HS. METHODS: Retrospective case series of 12 dogs with histologically diagnosed HS metastatic to lymph nodes treated with surgery with and without adjuvant chemotherapy. RESULTS: All dogs had histological evidence of metastasis to lymph nodes, with no clinical evidence for metastasis to viscera. Eight dogs that received chemotherapy had a median estimated survival of 219 days (range 77-1638 days); 1- and 2-year estimated survival rates were 37.7%. Median survival time for 4 dogs with nodal metastases that did not receive chemotherapy was 57 days (range 39-136 days) with none alive 1 year after surgery CONCLUSION: Survival for dogs with only regional nodal metastases from HS appeared to be improved by adjuvant chemotherapy.
Asunto(s)
Quimioterapia Adyuvante/veterinaria , Enfermedades de los Perros/tratamiento farmacológico , Sarcoma Histiocítico/veterinaria , Animales , Enfermedades de los Perros/patología , Enfermedades de los Perros/cirugía , Perros , Femenino , Sarcoma Histiocítico/tratamiento farmacológico , Sarcoma Histiocítico/patología , Sarcoma Histiocítico/cirugía , Ganglios Linfáticos/patología , Metástasis Linfática , Masculino , Pronóstico , Estudios Retrospectivos , Sobrevida , Análisis de SupervivenciaRESUMEN
Many chemotherapy drugs used in human patients are discarded after single use or within 24 h of reconstitution, as per the manufacturer's product label recommendations. This can be wasteful and costly to veterinary clients. This report reviews the published stability and storage data for 19 injectable chemotherapy drugs commonly used in veterinary medicine. Based on these data, storage procedures are presented, assuming aseptic technique and a closed system drug transfer device (CSDTD) are used for drug preparation and handling. Further studies on the risk of microbiological contamination of chemotherapeutics using a CSDTD, and validated high quality drug assays such as stability-indicating high-performance liquid chromatography, are required. The authors' intent is not to supersede product label recommendations, but to suggest that longer storage without significant loss of drug efficacy may be possible, thus reducing the costs of chemotherapeutics to some veterinary clients.
Asunto(s)
Estabilidad de Medicamentos , Almacenaje de Medicamentos , Drogas Veterinarias , Animales , Antineoplásicos/administración & dosificación , Inyecciones , Drogas Veterinarias/administración & dosificaciónRESUMEN
This retrospective study identified prognostic factors associated with survival; and compared survival data in 94 canine mammary carcinoma (MCA) dogs treated with surgery (n = 58), or surgery and adjunct chemotherapy (n = 36), and a subset of dogs with poor prognostic factors. On multivariate analysis independent predictors of median survival time (MST) were clinical stage, lymphatic invasion (LI; present 179 days; none 1098 days), ulceration (present 118 days; none 443 days) and surgical margins (incomplete 70 days; complete 872 days). Complete surgical margins were associated with MST in dogs with stages 1-3 MCA (incomplete 68 days; complete 1098 days) and dogs with LI (incomplete 70 days; complete 347 days). There was no statistically significant improvement in MST in dogs with advanced disease (stage 4 or LI) treated with adjunctive chemotherapy (chemotherapy 228 days; none 194 days); although five dogs with complete surgical margins that received mitoxantrone and carboplatin had a mean survival of 1139 days.
Asunto(s)
Antineoplásicos/uso terapéutico , Carcinoma/veterinaria , Enfermedades de los Perros/cirugía , Neoplasias Mamarias Animales/cirugía , Animales , Antineoplásicos/administración & dosificación , Carcinoma/patología , Carcinoma/cirugía , Quimioterapia Adyuvante/veterinaria , Enfermedades de los Perros/tratamiento farmacológico , Enfermedades de los Perros/patología , Perros , Femenino , Neoplasias Mamarias Animales/patología , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Splenic fibrohistiocytic nodules (SFHN) are commonly diagnosed. It is suspected that these represent a heterogeneous group of malignant and nonmalignant diseases, separation of which could improve the ability of clinicians to prognosticate for dogs. HYPOTHESIS/OBJECTIVES: Immunohistochemistry will differentiate histologic diagnoses within the group of SFHN; survival after splenectomy is associated with those histologic types. ANIMALS: Thirty-two dogs with SFHN treated by or under direction from veterinary oncologists. METHODS: Retrospective case record analysis from dogs followed from splenectomy until death. Clinical, histopathologic, and immunohistochemistry data analyzed for an association with survival time. RESULTS: Thirty-two dogs had SFHN; grade 1 (2 dogs), grade 2 (9 dogs), and grade 3 (lymphoid percentage <40%; 21 dogs). Twenty-two dogs died, 10 were censored (9 alive median of 883 days after splenectomy). Median overall survival was 387 days, and grade 3 SFHN was negatively [corrected] associated with survival time as previously reported (P < .001). Of 31 available samples, dogs had diseases reclassified as nodular hyperplasia (13; 8 complex, 5 lymphoid including 2 marginal zone), lymphoma (4; 2 marginal zone lymphoma, 1 high grade B-cell lymphoma, and 1 marginal zone transitional to high grade B-cell lymphoma), 8 stromal sarcomas, and 6 histiocytic sarcomas. Dogs with histiocytic sarcoma had worse survival (median 74 days) than dogs with other diseases. CONCLUSIONS AND CLINICAL IMPORTANCE: Splenic histiocytic sarcoma is an aggressive disease; however, some dogs with stromal sarcomas had long survival times. The term SFHN is no longer warranted for this group of disorders.
Asunto(s)
Enfermedades de los Perros/patología , Sarcoma Histiocítico/veterinaria , Neoplasias del Bazo/veterinaria , Animales , Enfermedades de los Perros/metabolismo , Enfermedades de los Perros/cirugía , Perros , Femenino , Sarcoma Histiocítico/metabolismo , Sarcoma Histiocítico/patología , Sarcoma Histiocítico/cirugía , Inmunohistoquímica , Estimación de Kaplan-Meier , Masculino , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Esplenectomía/veterinaria , Neoplasias del Bazo/metabolismo , Neoplasias del Bazo/patología , Neoplasias del Bazo/cirugíaRESUMEN
The efficacy and toxicity of orthovoltage radiation therapy and concurrent low doses of doxorubicin for the treatment of incompletely excised soft-tissue sarcomas in 39 dogs was investigated retrospectively. The 39 dogs had 40 soft-tissue sarcomas and received 51 Gy orthovoltage radiation in 17 daily 3 Gy fractions; they also received 10 mg/m(2) doxorubicin once a week administered intravenously one hour before the dose of radiation. The median follow-up time was 910 days. The tumours recurred locally in seven of the dogs, in five of them within the radiation field; the median time to their recurrence was 213 days (range 63 to 555 days). Six of the dogs developed a distant metastasis after a median time of 276 days (range eight to 826 days). The one-year and two- to four-year tumour control rates were 84 per cent and 81 per cent, respectively, and the one-, two- and three- to four-year survival rates were 85 per cent, 79 per cent and 72 per cent, respectively. Tumours with a mitotic rate of more than 9 per 10 high-power fields were significantly more likely to recur, and the dogs with such tumours survived for significantly shorter periods.
Asunto(s)
Antineoplásicos/administración & dosificación , Enfermedades de los Perros/tratamiento farmacológico , Enfermedades de los Perros/radioterapia , Doxorrubicina/administración & dosificación , Recurrencia Local de Neoplasia/veterinaria , Sarcoma/veterinaria , Neoplasias de los Tejidos Blandos/veterinaria , Animales , Terapia Combinada/veterinaria , Supervivencia sin Enfermedad , Enfermedades de los Perros/mortalidad , Enfermedades de los Perros/patología , Enfermedades de los Perros/cirugía , Perros , Femenino , Infusiones Intravenosas/veterinaria , Masculino , Massachusetts , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/radioterapia , Dosis de Radiación , Registros/veterinaria , Estudios Retrospectivos , Sarcoma/tratamiento farmacológico , Sarcoma/radioterapia , Neoplasias de los Tejidos Blandos/tratamiento farmacológico , Neoplasias de los Tejidos Blandos/radioterapia , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
Seven client owned dogs with confirmed relapsed lymphoma were enrolled in a prospective feasibility study investigating the effects of low-dose total body irradiation (LDTBI) delivered in a single 1 Gy fraction. LDTBI for relapsed lymphoma was safe and well tolerated. The only major side-effect of LDTBI was asymptomatic thrombocytopenia in all dogs. The median platelet nadir was 17,000/microL (range 4000-89,000), which occurred a median of 10 days (range 8-30) post irradiation. Three dogs had short-term partial responses, two stable disease and two progressive disease (PD). Six dogs were euthanatized for PD, and one dog died while in partial remission. No dogs had clinical complications. Survival analysis was not performed, because the study design did not allow for evaluation of survival time. Larger studies incorporating LDTBI in the induction/consolidation phase of treatment need to be performed to determine the therapeutic efficacy of LDTBI.
RESUMEN
A retrospective analysis was done to assess the toxicity and efficacy associated with an alternating chemotherapy protocol of ifosfamide (375 mg m(-2)) and doxorubicin (30 mg m(-2)) for adjuvant treatment of 39 dogs with sarcomas. Twelve dogs had various soft-tissue sarcomas and 27 dogs had hemangiosarcoma (HSA). Complete blood counts were evaluated 7 days after the first dose of ifosfamide and doxorubicin. One dog had grade 4 neutropenia (<500 microL(-1)) after treatment with ifosfamide and one dog had grade 3 neutropenia (500-1000 microL(-1)) after treatment with doxorubicin. One dog treated with doxorubicin was hospitalized for 24 h due to vomiting. The median survival time (ST) for the 27 dogs with HSA treated by surgery and with doxorubicin/ifosfamide was 149 days (mean 366 days). Although the protocol of alternating ifosfamide and doxorubicin was well tolerated, it failed to result in a statistically significant improvement in the ST when compared to a historical population of dogs with stage 2 splenic HSA treated by surgery alone.
RESUMEN
Hematopoietic stem cell (HSC) homing is believed to rely heavily on adhesion interactions between stem cells and stroma. An in vitro assay was developed for adhesion of engraftable HSCs in bone marrow suspensions to pre-established Dexter-type long-term bone marrow culture stromal layers. The cell numbers in the adherent layer and supernatant were examined, along with the engraftment capability of adherent layer cells to indicate the number of HSCs that homed to in vitro stroma. The cell number in the supernatant declined over the 24-hour period. The number of test cells adhering to the stromal layer increased during the first hour and then fell at 6 and 24 hours. The number of test HSCs adhering to the stromal layer was substantial at 20 minutes, increased during the first hour, and then remained constant at 1, 6, and 24 hours of adhesion. These data indicate that adhesion of engraftable HSCs occurs quickly and increases during the first hour of contact with pre-established stroma, that adhesion plateaus within 1 hour of contact, and that HSCs maintain their engraftment capability for at least 24 hours of stromal adhesion. Long-term engraftment from test cells at more than 1 hour of adhesion represents 70.7% of the predicted engraftment from equivalent numbers of unmanipulated marrow cells, indicating that 2 of 3 test engraftable HSCs adhered. These findings demonstrate the usefulness of this model system for studying stem-stromal adhesion, allowing further dissection of the mechanism of HSC homing and exploration of possible manipulations of the process. (Blood. 2001;98:1012-1018)
Asunto(s)
Movimiento Celular/fisiología , Células Madre Hematopoyéticas/fisiología , Modelos Biológicos , Animales , Células de la Médula Ósea , Adhesión Celular , Recuento de Células , Técnicas de Cocultivo , Femenino , Supervivencia de Injerto , Trasplante de Células Madre Hematopoyéticas , Células Madre Hematopoyéticas/citología , Masculino , Ratones , Ratones Endogámicos BALB C , Células del Estroma/citología , Quimera por TrasplanteRESUMEN
Eighty-two dogs with lymphoma received a single 15-week course of chemotherapy, after which treatment was ceased until relapse. Fifty-six dogs (68%) achieved complete remission for a median 1st remission duration of 20 weeks. Forty-eight dogs relapsed, of which 30 repeated the induction cycle. In 22 of these dogs, 1st remission had been short, and they received maintenance chemotherapy; the other 8 dogs received 2 or 3 cycles of induction chemotherapy. Second remission rate for these 30 dogs was 87% (26 dogs). Overall disease control for the 38 dogs that remained on protocol was 44 weeks, which was not markedly shorter than for dogs treated with a previously reported protocol in which maintenance chemotherapy was instituted in all dogs after an identical 1st induction (VELCAP-L). Dogs that were febrile and dogs that were dyspneic were less likely to achieve a complete remission to induction chemotherapy. Of dogs that achieved a complete remission, those that were thrombocytopenic at entry had a shorter 1st remission, and dogs that were anorexic at entry had shorter overall disease control. There was a correlation between 1st remission duration and length of any subsequent remission obtained. The incidence of toxicity was high, particularly after the combination of doxorubicin and vincristine. Dose reductions because of toxicity did not markedly reduce remission duration. We conclude that discontinuous chemotherapy may reduce patient visits in a small number of patients because of long-term disease control. Delaying maintenance chemotherapy until after 2nd remission is achieved does not markedly affect overall disease control.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Enfermedades de los Perros/tratamiento farmacológico , Linfoma/veterinaria , Animales , Asparaginasa/administración & dosificación , Cruzamiento , Ciclofosfamida/administración & dosificación , Supervivencia sin Enfermedad , Perros , Doxorrubicina/administración & dosificación , Esquema de Medicación , Femenino , Linfoma/tratamiento farmacológico , Masculino , Prednisona/administración & dosificación , Registros/veterinaria , Estudios Retrospectivos , Resultado del Tratamiento , Vincristina/administración & dosificaciónRESUMEN
OBJECTIVE: Long-term bone marrow cultures (LTBMC) are a potential source of hematopoietic stem cells (HSC) for transplantation. Previous reports indicate that feeding LTBMCs induces hematopoietic progenitor cycling, and other studies link HSC cycle phase with engraftability. Our study was initiated to further characterize LTBMC engraftability and determine if a cycle phase-related engraftment defect affects HSC from LTBMCs. MATERIALS AND METHODS: Competitive repopulation of lethally irradiated BALB/c females was used to examine engraftability of LTBMCs under "fed" or "unfed" conditions at 3 to 5 weeks culture. Tritiated thymidine suicide was used to determine the cycle status of HPP-CFC and CFU-S from LTBMCs. RESULTS: Total cell number in LTBMCs decreases from input. Quantitatively, both fed and unfed 3-, 4-, or 5-week cultures compete strongly with fresh marrow for 2 and 8 weeks, but not 6 months, after transplantation. Short-term engraftable HSCs expand between 3 and 5 weeks of culture. Clonal assays indicate no peak in S-phase of CFU-S at 24 and 48 hours after feeding, and fluctuation in both content and cycle status of HPP-CFC after feeding. CONCLUSIONS: Our LTBMCs engraft in all conditions, and the level of engraftment capability does not correlate with cell-cycle phase of CFU-S or HPP-CFC, or with time from feeding. Although the total cell number decreases from input, the proportion of short- and intermediate-term engrafting HSC in whole LTBMCs approximates that of fresh marrow and expands from 3 to 5 weeks in culture, whereas long-term engraftable HSCs are decreased in culture.
Asunto(s)
Células de la Médula Ósea/citología , Trasplante de Células Madre Hematopoyéticas , Células Madre Hematopoyéticas/citología , Animales , Técnicas de Cultivo de Célula/métodos , Ciclo Celular , Células Cultivadas/trasplante , Medios de Cultivo/farmacología , Femenino , Supervivencia de Injerto , Masculino , Ratones , Ratones Endogámicos BALB C , Quimera por Radiación , Factores de TiempoRESUMEN
Haematopoietic stem cells (HSCs) have been extensively characterized regarding in vivo engraftment, surface epitopes and genetic regulation. However, little is known about the homing of these rare cells, and their intrinsic motility and membrane deformation capacity. We used high-speed optical-sectioning microscopy and inverted fluorescent videomicroscopy to study highly purified murine lineage-negative, rhodamine-low, Hoechst-low HSCs over time under various in vitro conditions. We discovered extremely rapid motility, directed migration to stromal cells and marked membrane modulation. High resolution images with three-dimensional reconstruction showed the general presence of microspikes. Further, pseudopodia (proteopodia) were observed that were induced by stromal-derived factor-1 and steel factor. Proteopodia were directed towards and were quenched by stromal cells, at times bridged HSCs, and could rapidly retract or detach from cells. Proteopodia were also observed in vivo with homed HSCs in frozen sections of murine spleen, lung and heart. This is the first demonstration that HSCs are both fast and highly malleable in phenotype.
Asunto(s)
Extensiones de la Superficie Celular/ultraestructura , Células Madre Hematopoyéticas/fisiología , Animales , Células de la Médula Ósea , Adhesión Celular , Comunicación Celular , Movimiento Celular , Separación Celular , Extensiones de la Superficie Celular/efectos de los fármacos , Células Cultivadas , Quimiocina CXCL12 , Quimiocinas CXC/farmacología , Técnicas de Cocultivo , Femenino , Células Madre Hematopoyéticas/efectos de los fármacos , Células Madre Hematopoyéticas/ultraestructura , Procesamiento de Imagen Asistido por Computador , Ratones , Ratones Endogámicos BALB C , Microscopía Electrónica , Microscopía Fluorescente , Microscopía por Video , Factor de Células Madre/farmacologíaRESUMEN
lfosfamide (3-[2-chloroethyl]-2[(2 chloroethyl)amino]tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide) is an alkylating agent with a broad spectrum of antitumor activity. The efficacy and toxicity of ifosfamide were evaluated in 72 dogs with spontaneously occurring tumors. Forty dogs (56%) had lymphoma, 31 (43%) had sarcomas, and 1 had a metastatic carcinoma. Five dogs received ifosfamide at dosages <350 mg/m2 IV. Neither toxicity nor response were observed, and the remaining dogs received ifosfamide at 350 mg/m2 (n = 18) and 375 mg/m2 body surface area IV (n = 49). Saline diuresis and the thiol compound mesna were used to prevent urothelial toxicity. Fifty-two dogs had measurable tumors and could be evaluated for response. Complete responses were seen in 1 dog with metastatic leiomyosarcoma of the urinary bladder and in 1 dog with metastatic cutaneous hemangiosarcoma. One dog with lymphoma had a partial response for 112 days. Six dogs with splenic hemangiosarcoma received ifosfamide postsplenectomy and their median survival time was 147 days. The acute dose limiting toxicity was neutropenia 7 days after administration of ifosfamide. The median and mean neutrophil counts 7 days after ifosfamide at 350 mg/m2 were 2,035 cells/microL and 4,773 cells/microL, respectively (n = 12). The median and mean neutrophil counts 7 days after ifosfamide at 375 mg/m2 were 2,500 cells/microL and 3,594 cells/microL, respectively (n = 37). No dog developed clinical or microscopic evidence of hemorrhagic cystitis. Ifosfamide appears safe to use in tumor-bearing dogs, and the evaluation of combination chemotherapy protocols that include ifosfamide should be considered.
Asunto(s)
Antineoplásicos Alquilantes/uso terapéutico , Enfermedades de los Perros/tratamiento farmacológico , Ifosfamida/uso terapéutico , Linfoma/veterinaria , Sarcoma/veterinaria , Animales , Enfermedades de los Perros/mortalidad , Perros , Femenino , Linfoma/tratamiento farmacológico , Linfoma/mortalidad , Masculino , Massachusetts/epidemiología , Registros/veterinaria , Estudios Retrospectivos , Sarcoma/tratamiento farmacológico , Sarcoma/mortalidad , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
Forty-three dogs with lymphoma that had relapsed or had failed to achieve complete remission to previous chemotherapy were treated with lomustine (1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea [CCNU]) at a dosage of 90-100 mg/m2 body surface area p.o. every 3 weeks. Durable complete or partial responses occurred in 11 dogs for a median of 86 days. The acutely dose-limiting toxicosis was neutropenia 7 days after administration, resulting in a recommended dosage of 90 mg/m2. Cumulative thrombocytopenia occurred in dogs receiving continued CCNU treatment, and a dose interval of 3 weeks may be too short for continued administration of this drug. Toxicoses evident as fever or central nervous system signs or renal damage were uncommon or rare. CCNU is effective in the treatment of relapsed lymphoma.
Asunto(s)
Antineoplásicos Alquilantes/uso terapéutico , Enfermedades de los Perros/tratamiento farmacológico , Lomustina/uso terapéutico , Linfoma/veterinaria , Animales , Antineoplásicos Alquilantes/efectos adversos , Perros , Resistencia a Antineoplásicos , Femenino , Lomustina/efectos adversos , Linfoma/tratamiento farmacológico , Masculino , Neutropenia/inducido químicamente , Recurrencia , Trombocitopenia/inducido químicamente , Resultado del TratamientoRESUMEN
Ninety-eight dogs with lymphoma treated with a 5-drug combination chemotherapy regimen (vincristine, L-asparaginase, cyclophosphamide, doxorubicin, prednisone [VELCAP-L]) were evaluated for pretreatment characteristics predictive for response and remission duration. The complete remission rate was 69%, with a median remission duration of 55 weeks. Dogs with advanced stage of disease, constitutional signs, dogs that were older, and dogs that were dyspneic were less likely to achieve remission. Once in remission, small dogs and dogs without pretreatment thrombocytopenia were likely to have longer remission duration. Toxicoses were frequent, but rarely fatal, and no predictitive factors were found for a dog developing toxicoses. VELCAP-L is an effective treatment for dogs in stage I-III lymphoma, particularly in young, small animals.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Enfermedades de los Perros/tratamiento farmacológico , Linfoma/veterinaria , Factores de Edad , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Asparaginasa/administración & dosificación , Asparaginasa/efectos adversos , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Perros , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Femenino , Linfoma/tratamiento farmacológico , Masculino , Estadificación de Neoplasias/veterinaria , Prednisona/administración & dosificación , Prednisona/efectos adversos , Pronóstico , Inducción de Remisión , Factores Sexuales , Resultado del Tratamiento , Vincristina/administración & dosificación , Vincristina/efectos adversosRESUMEN
Five Rottweiler puppies from 3 unrelated litters developed inspiratory stridor at 11-13 weeks of age. Physical examination disclosed tetraparesis in all dogs, and bilateral lenticular cataracts in 4 dogs. Laryngeal examination under light anesthesia showed laryngeal paralysis in all dogs. Electrodiagnostic testing revealed denervation potentials in the distal appendicular muscles of 4 dogs tested and in the intrinsic laryngeal muscles of 2 dogs tested. Motor nerve conduction velocity was slightly low in 1 dog. Neurogenic muscular atrophy was found in distal appendicular muscles (n = 3) and intrinsic laryngeal muscles (n = 2), and degenerative changes were found in peripheral nerves (n = 3) and recurrent laryngeal nerves (n = 2). No abnormalities were detected in the spinal cord, spinal nerve roots, or ganglia of 3 dogs autopsied. The clinical, electrophysiologic, and histopathologic findings support a diagnosis of polyneuropathy and resemble the finding reported in young Dalmatians. Young dogs with laryngeal paralysis should be evaluated neurologically to rule out a more generalized polyneuropathy. The condition is suspected to be hereditary in nature and the prognosis is poor.
Asunto(s)
Enfermedades de los Perros/patología , Enfermedades del Sistema Nervioso Periférico/veterinaria , Parálisis de los Pliegues Vocales/veterinaria , Animales , Enfermedades de los Perros/congénito , Perros , Femenino , Nervios Laríngeos/patología , Laringe/patología , Masculino , Enfermedades del Sistema Nervioso Periférico/congénito , Pronóstico , Parálisis de los Pliegues Vocales/congénitoRESUMEN
5-Ethylamino-9-diethylaminobenzo[a]phenothiazinium chloride (EtNBS) is a novel photodynamic therapy (PDT) photosensitizer with efficacy against experimental murine tumors. In this preliminary study, dogs and cats with naturally occurring tumors were treated with EtNBS-PDT to determine safety and efficacy. Fifteen treatments were performed on 13 animals (9 treatments in 8 cats and 6 treatments in 5 dogs), generally using 400 J of 652 nm light. Two feline sublingual squamous cell carcinomas (SCCs) responded briefly (minor response). Six feline facial SCCs were treated, resulting in two partial responses and four long-term complete responses (CR). Two canine intraoral SCCs were treated; one responded minimally for 2 weeks (minor response), and one achieved long-term CR. One canine cutaneous mast cell tumor achieved CR, and one canine ocular mast cell tumor responded briefly. One canine ocular melanoma did not respond to treatment. Systemic reactions included nausea associated with photosensitizer injection in two cats and two dogs, elevated body temperatures during treatment in two dogs, elevated body temperature 2 days after PDT in one cat, and inappetance for 2 weeks in one cat. A peripheral neuropathy of undetermined cause occurred in one cat 2 weeks after PDT and resolved without treatment. Local reaction was well tolerated in 13 of 15 treatments. All animals were exposed to normal daylight after less than 5 days (mean, 3.5 days) without residual photosensitization. EtNBS-PDT is safe for dogs and cats and has activity against selected naturally occurring tumors, with an overall objective response rate (partial response + CR) of 61.5%.
Asunto(s)
Antineoplásicos/uso terapéutico , Enfermedades de los Gatos/tratamiento farmacológico , Enfermedades de los Perros/tratamiento farmacológico , Neoplasias/veterinaria , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/uso terapéutico , Tiazinas/uso terapéutico , Animales , Antineoplásicos/efectos adversos , Carcinoma de Células Escamosas/veterinaria , Gatos , Perros , Neoplasias Faciales/veterinaria , Femenino , Masculino , Sarcoma de Mastocitos/veterinaria , Neoplasias de la Boca/veterinaria , Fármacos Fotosensibilizantes/efectos adversos , Neoplasias Cutáneas/veterinaria , Tiazinas/efectos adversosRESUMEN
The most primitive engrafting hematopoietic stem cell has been assumed to have a fixed phenotype, with changes in engraftment and renewal potential occurring in a stepwise irreversible fashion linked with differentiation. Recent work shows that in vitro cytokine stimulation of murine marrow cells induces cell cycle transit of primitive stem cells, taking 40 h for progression from G0 to mitosis and 12 h for subsequent doublings. At 48 h of culture, progenitors are expanded, but stem cell engraftment is markedly diminished. We have investigated whether this effect on engraftment was an irreversible step or a reversible plastic feature correlated with cell cycle progression. Long-term engraftment (2 and 6 mo) of male BALB/c marrow cells exposed in vitro to interleukin (IL)-3, IL-6, IL-11, and steel factor was assessed at 2-4-h intervals of culture over 24-48 h using irradiated female hosts; the engraftment phenotype showed marked fluctuations over 2-4-h intervals, with engraftment nadirs occurring in late S and early G2. These data show that early stem cell regulation is cell cycle based, and have critical implications for strategies for stem cell expansion and engraftment or gene therapy, since position in cell cycle will determine whether effective engraftment occurs in either setting.
Asunto(s)
Ciclo Celular/fisiología , Trasplante de Células Madre Hematopoyéticas , Células Madre Hematopoyéticas/citología , Células Madre Hematopoyéticas/fisiología , Animales , Ciclo Celular/efectos de los fármacos , Células Cultivadas , Citocinas/farmacología , Femenino , Masculino , Ratones , Ratones Endogámicos BALB CRESUMEN
Thirty-seven dogs with moderately differentiated, cutaneous mast cell tumors had incomplete surgical excisions as determined by histopathology, but no gross evidence of tumor. All dogs were irradiated to a total dose of between 46.2 and 48.0 Gy using either an orthovoltage source (n = 20) or a linear accelerator (megavoltage) (n = 17). Radiation was delivered to an area bordered by margins of 3 cm or greater around the surgical scar. The mast cell tumors had not recurred in 97% of dogs by one year after radiation therapy and had not recurred in 93% of dogs by three years after radiation. Both orthovoltage and megavoltage radiation provide excellent local control of moderately differentiated mast cell tumors in dogs.