Phase I clinical evaluation of carboplatin in tumor-bearing cats: a Veterinary Cooperative Oncology Group study.

Background: The dosage of carboplatin in cats has been reported anecdotally and experimentally in non-tumor-bearing cats, but the dosage for carboplatin treatment in tumor-bearing cats has yet to be defined in a prospective clinical trial.

Purpose: To determine the maximally tolerated dose (MTD) and dose-limiting toxicosis (DLT) of carboplatin in tumor-bearing cats. CATS: Fifty-nine cats with measurable solid tumors.

Liposome-encapsulated doxorubicin (Doxil) and doxorubicin in the treatment of vaccine-associated sarcoma in cats.

The purpose of this randomized, multicenter study was to evaluate the toxicity and efficacy of liposome-encapsulated doxorubicin (LED) and doxorubicin (DOX) in the treatment of feline vaccine-associated sarcoma (VAS). Cats were divided according to their disease status into a microscopic arm (no evidence of gross disease) and a macroscopic arm (evidence of gross disease). Each arm was randomized to receive either LED (1-1.

Adoptive therapy of canine metastatic mammary carcinoma with the human MHC non-restricted cytotoxic T-cell line TALL-104.

Adoptive transfer of human TALL-104 killer cells into a dog with metastatic mammary adenocarcinoma resulted in 50% reduction of the largest lung metastasis and stabilization of the other lesions for 10 weeks, accompanied by the development of tumor-specific immune responses. Upon halting cell therapy, the dog developed new lung lesions within 10 weeks and died of slowly progressive disease. TALL-104 cell therapy of mice bearing the dog's tumor xenograft induced 65% reduction of local tumor growth and regression of lung metastases in 100% of the animals.

Adjuvant treatment of canine osteosarcoma with the human cytotoxic T-cell line TALL-104.

The human cytotoxic T-cell line TALL-104 has been used successfully to treat cancer in experimental mouse models with implanted tumors and in dogs with spontaneously occurring malignancies. This study investigated the efficacy of TALL-104 cells given in an adjuvant setting to dogs with appendicular osteosarcoma after surgery and chemotherapy. Of the 23 dogs enrolled in the study, 20 had undergone amputation of the affected limb, and 3 had undergone limb salvage surgery.

Successful treatment of canine malignant histiocytosis with the human major histocompatibility complex nonrestricted cytotoxic T-cell line TALL-104.

The human MHC nonrestricted cytotoxic T-cell line TALL-104 exerts potent antitumor effects in animal models with both induced and spontaneous cancers. The present report documents the ability of systemically delivered TALL-104 cells to induce durable clinical remissions in four of four dogs with malignant histiocytosis (MH). The animals received multiple i.

Toxicological and immunological evaluation of the MHC-non-restricted cytotoxic T cell line TALL-104.

The human MHC-non-restricted cytotoxic T cell line TALL-104 has been shown to display potent antitumor effects in several animal models with spontaneous and induced malignancies. In view of its potential future use in cancer therapy, we investigated the tolerability and target-organ toxicity of these cells in various animal species. The acute toxicity of TALL-104 cell administrations was evaluated in: (a) healthy immunocompetent mice and immunodeficient (SCID) mice bearing human tumors using multiple (up to 15) intraperitoneal (i.

Phase I clinical trial with a human major histocompatibility complex nonrestricted cytotoxic T-cell line (TALL-104) in dogs with advanced tumors.

The human TALL-104 cell line is endowed with a uniquely potent MHC nonrestricted tumoricidal activity across several species. In view of the potential applicability of TALL-104 cells as an anticancer agent, this study was conducted to evaluate the possible toxicity and efficacy of this new cell therapy in a superior animal model with spontaneous tumors. Nineteen canine cases with advanced, refractory malignancies of various histological types were entered in the study.

Oral tumors: the surgeon and the medical oncologist.

Aggressive surgery has been the primary treatment for oral tumors through the 1980s. A review of the results of such treatment is presented. A new approach using neoadjuvant chemotherapy is proposed in order to improve long-term prognosis in malignant oral tumors.

Chemoimmunotherapy of canine lymphoma with adjuvant canine monoclonal antibody 231.

Chemoimmunotherapy with adjuvant CL/MAb 231 offers an alternative treatment approach for canine lymphoma. Results of treatment and prognostic factors are discussed and compared with previously published chemotherapy results.

Malignant angioendotheliomatosis with retinal detachments in a dog.

A Golden Retriever with bilateral conjunctival hyperemia, chemosis, and blepharospasm was determined to have malignant angioendotheliomatosis, which is an uncommon neoplastic disorder of dogs and human beings. It was believed to be of endothelial origin, but evidence in human beings indicates a lymphoid origin. The histogenesis of the disease in the dog was confirmed to be of lymphoid origin by use of a canine lymphoma-specific immunoperoxidase assay.

Chemotherapy of canine hemangiosarcoma with doxorubicin and cyclophosphamide.

Sixteen dogs with a histologic diagnosis of hemangiosarcoma were treated with surgery and doxorubicin/cyclophosphamide. The patients' characteristics, ie, age, size, and breed, were similar to those of previous studies. Historic controls for surgery alone were used to evaluate efficacy of the chemotherapy.

Treatment of relapsed canine lymphoma with doxorubicin and dacarbazine.

Fifteen dogs with relapsed lymphoma were treated with doxorubicin and dacarbazine (ADIC) to reinduce remission. All the dogs' lymphomas had become resistant to prior therapy with doxorubicin alone. Five of the 15 dogs had a complete response to the first treatment with ADIC, and three had partial responses.

In vivo destruction of canine lymphoma mediated by murine monoclonal antibodies.

The effect of murine anti-canine lymphoma monoclonal antibodies (MAbs) on tumor cell lysis by thioglycolate activated murine macrophages in vitro and tumor growth inhibition in athymic mice was studied. All IgG1 and IgG2a MAbs tested were able to promote specific destruction of canine lymphoma 17-71 cell line by activated macrophages. A correlation between higher ADCC activity and MAb isotype was not clearly evident.

In vitro immune monitoring of antibody response in dogs given chemoimmunotherapy for lymphoma.

Clinical remission in 30 dogs with lymphoma was induced with a combination of vincristine, L-asparaginase, cyclophosphamide, and doxorubicin HCl, administered sequentially, and then an autochthonous tumor cell vaccine, given intralymphatically, as maintenance therapy. Humoral antibody amounts were monitored in 11 dogs, using a solid-phase bead-type radioimmunoassay. The median survival of the 30 dogs was 13 months from the start of chemotherapy (range, 7 to 25 months; mean, 13.

Cytolytic activity of murine anti-dog lymphoma monoclonal antibodies with canine effector cells and complement.

Peripheral blood leukocytes (PBL), nonadherent lymphocytes, and adherent monocytes separated from freshly isolated blood of 15 dogs were analyzed for their ability to mediate antibody-dependent cell-mediated cytotoxicity (ADCC) in combination with murine anti-tumor monoclonal antibodies (MAbs). Canine monocytes isolated from most donors by adherence to gelatin-fibronectin-coated plastic surface presented high ADCC activity against the canine lymphoma 17-71 tumor cell line in combination with antilymphoma MAbs 231 (IgG2a) and 234-2a (IgG2a). Canine lymphocytes generally showed lower ADCC activity than total PBL or monocytes.

Chemotherapy versus chemotherapy with intralymphatic tumor cell vaccine in canine lymphoma.

Fifty-eight dogs with lymphoma were treated with combination chemotherapy (vincristine, cyclophosphamide, L-asparaginase, and doxorubicin HCl [VCAA]) followed by intralymphatic autochthonous tumor cell vaccine (CI). Thirty dogs received chemotherapy alone (VCAA). There was no overall significant difference in survival times between the two groups, although there was a trend toward prolonged survival in the CI group.

Chemotherapy of lymphoma in 75 cats.

Seventy-five cats with lymphoma were treated with combination sequential chemotherapy consisting of vincristine, cyclophosphamide, and methotrexate. Thirty-nine cats had mediastinal, 16 had multicentric, 14 had alimentary, and 6 had renal lymphoma. The median survival time of the 75 cats was 8 weeks, with a mean of 32 weeks.

Canine lymphoma-associated antigens defined by murine monoclonal antibodies.

Lymphoma in dogs resembles human non-Hodgkin's lymphoma in pathological presentation, immunophenotype, and response to therapy, thus representing a good model for comparative studies with human disease. Monoclonal antibodies (MAbs) were derived from mice immunized with a dog lymphoma cell line. Three MAbs were selected for further application in immunophenotyping and immunotherapy.

Intralymphatic autochthonous tumor cell vaccine in canine lymphoma.

Canine lymphoma is analogous to non-Hodgkin's lymphoma and is responsive to similar cytotoxic agents. The purpose of this study was to investigate a tumor cell vaccine delivered via peripheral lymphatics as maintenance therapy after induction of remission with chemotherapy. Thirty dogs with histologically confirmed lymphoma were treated with chemoimmunotherapy, and were induced into remission with combination chemotherapy, followed by intralymphatic (IL) autochthonous tumor cell vaccines as maintenance therapy.

Chemotherapy of advanced mammary adenocarcinoma in 14 cats.

Fourteen cats with advanced mammary adenocarcinoma were treated with doxorubicin HCl and cyclophosphamide. All cats had inoperable or recurrent disease, and 9 cats had metastasis to the thorax. Eleven of the cats were available for long-term evaluation; 3 had complete response to chemotherapy, with survival times of 180, 283, and 344 days; 2 had partial response, with survival times of 45 and 149 days; 2 had stabilization of disease, with survival times of 170 and 182 days; and 4 had no response, with survival times of 4, 47, 67, and 106 days.

Immunomodulation of hematopoietic tumors.

Immunotherapy has been used in a variety of hematopoietic and solid tumors. Because patients with leukemia and lymphoma are immunosuppressed, immunomodulation with chemotherapy may be beneficial. Chemoimmunotherapy of canine lymphoma is discussed.

Enhanced antitumor effects with intralymphatic delivery using bacillus Calmette-Guerin in animal models.

This study compares the effectiveness of various routes of administration of Bacillus Calmette-Guerin (BCG) utilizing the New Zealand white (NZW) rabbit V2 carcinoma model. The routes compared were intratumor, intravenous, scarification, subcutaneous, and intralymphatic. Primary tumor regression, disease-free interval, and survival were measured.

Malignant pilomatricoma in a dog.

A malignant pilomatricoma is described in a dog. The primary tumor apparently developed in the metatarsal area where there were multiple intradermal skin nodules. Lymphatic invasion by tumor cells resulted in metastasis to the mammary glands, lymph nodes and lungs.

Intralymphatic BCG in the treatment of gynecologic malignancies: a phase I study.

Thirteen patients with a variety of advanced gynecologic malignancies were administered BCG via the dorsal lymphatics of the lower extremity in addition to standard accepted forms of therapy. Prolonged febrile courses, lymphangitis and suppurative adenitis were observed along the lymphatic pathway of the injected lower limbs. There was no correlation between reaction to a standard anergy panel and survival.