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.     

BONE SARCOMA FOLLOWING ORTHOVOLTAGE RADIOTHERAPY IN TWO DOGS

In two dogs that received orthovoltage radiotherapy, osteosarcoma developed in irradiated bone 38 and 77 months after treatment. Irridiated bone in one dog was presumably normal prior to radiotherapy; irradiated bone in the other was infiltrated by an acanthomatous epulis. Both osteosarcomas were probably radiation induced. Radiation-induced bone sarcoma is an important, but uncommon, complication of radiaotherapy.     

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 (1-1.5 mg/kg i.v. q3 weeks) or DOX (1 mg/kg i.v. q3 weeks). Thirty-three cats were entered in the macroscopic arm of the study with an overall response rate of 39% (5 complete response and 8 partial response) and a median time to progression of 84 days. Response rates were not different between LED and DOX. Seventy-five cats were entered into the microscopic arm. When compared to a similar historical control population treated with surgery alone, the cats receiving chemotherapy had a prolonged median disease-free interval (388 days versus 93 days). No difference in efficacy was detected between LED and DOX. LED at 1.5 mg/kg induced delayed nephrotoxicosis in 23%, necessitating a decrease in the recommended dosage to 1 mg/kg, and cutaneous toxicosis in 21.7% of treated cats. This study showed that both DOX and LED are efficacious in the treatment of VAS and should be considered in the treatment of this tumor.     

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, 13.8). The median remission duration was 16 weeks (range, 9 to 98 weeks; mean, 26.8). Correlation between increase in amount of humoral antibody was significant (P = 0.0001 to 0.012), before and after chemoimmunotherapy, in dogs responding to therapy, compared with that in dogs not responding to therapy.     

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. The results show a trend of improved survival in dogs with localized disease (Stage I) receiving combination therapy. The median survival was 250 days, with a mean of 403 days. The survival times for dogs with stage I, II, and III disease was also improved with combination therapy, when compared to historical controls treated with surgery alone. The overall median survival was 202 days with a mean of 285 days. Toxicities included mild to moderate neutropenia (9 of 16) and clinical signs, such as lethargy, anorexia, vomiting, diarrhea, and fever (13 of 16). Three dogs had severe neutropenia requiring hospitalization and supportive care. One dog died from sepsis and related complications. Chemotherapy with doxorubicin and cyclophosphamide appears to improve survival with acceptable morbidity in patients with early stage disease. (Journal of Veterinary Internal Medicine 1993; 7:370–376. Copyright © 1993 by the American College of Veterinary Internal Medicine.)     

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. Sixty-two cats had follow-up evaluation until death or cure and had a median survival time of 7 weeks, with a mean of 37 weeks. Of the 62 cats, 32 (52%) attained complete remission, with a median remission duration of 16 weeks and a mean of 46 weeks. The addition of prednisolone and/or L-asparaginase to the protocol did not improve the results. Sixteen cats with multicentric lymphoma had the longest survival times (median, 18 months) and remission durations (median, 25 months). Prognostic factors were evaluated in each anatomic form of lymphoma.     

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. Of the eight dogs receiving a second cycle, two had complete responses, and one had a partial response. One dog that received a third ADIC treatment no longer responded. The median survival time from the first ADIC treatment for all dogs was 45 days (range, 18-241 days). The five dogs having complete responses to the first ADIC treatment had a median survival time of 105 days (range, 45-241 days) after this treatment. Toxicity due to ADIC treatment was acceptable and did not exceed that seen when doxorubicin was given as a single agent. The treatment resulted in severe neutropenia in three dogs. One dog died due to neutropenic sepsis. Vomiting, diarrhea, and anorexia occurred, but were tolerable, resulting in hospitalization in only one instance. ADIC is apparently a useful chemotherapeutic combination to reinduce remission in some dogs with relapsed lymphoma.     

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. METHODS: The starting dose of carboplatin was 160 mg/m(2) of body surface area IV. Doses were increased by 20 mg/m(2) in cohorts of 3-14 cats until the MTD was reached. RESULTS: The 59 cats entered into this multi-institutional phase I study received 1 or more doses of carboplatin at various dosages and were evaluated for toxicity, response to treatment, or both. The MTD was 240 mg/m(2) and neutropenia was the DLT. For the 1st cycle of treatment in 44 cats evaluated for neutropenia, 6 episodes of grade 3 or greater neutropenia occurred on days 7 (n=1), 14 (n=4), and 21 (n=1). There was no evidence of drug-induced nephrotoxicosis or pulmonary edema. Preliminary evidence of antitumor activity was observed in 7 of 59 (11.9%; 95% CI, 5.6-22.8%) cats evaluated for response to treatment. There was 1 complete response (cutaneous hemangiosarcoma) and 6 partial responses (4 injection site sarcomas, 1 oral squamous cell carcinoma, 1 lymphoma). Responses were of short duration (median, 42 days; range, 7-168 days). CONCLUSIONS AND CLINICAL IMPORTANCE: The dose of carboplatin recommended to treat tumor-bearing cats is 240 mg/m(2) IV every 3-4 weeks.