Use of surgery and electron beam irradiation, with or without chemotherapy, for treatment of vaccine-associated sarcomas in cats: 78 cases (1996-2000).

OBJECTIVE: To evaluate responses of cats with vaccine-associated sarcomas to treatment with surgery and radiotherapy, with or without adjunctive chemotherapy. DESIGN: Retrospective study. ANIMALS: 76 cats (78 tumors). PROCEDURE: Medical records were reviewed. Factors potentially associated with survival time, time to recurrence, and time to development of metastases were evaluated. RESULTS: Following excision, electron beam radiation, and, in some cases, chemotherapy, 32 (41%) cats experienced recurrence, and 9 (12%) cats developed metastases. One- and 2-year survival rates were 86 and 44%, respectively. Median survival time from onset of disease was 730 days (range, 30 to 2,014 days). Median disease-free interval was 405 days (range, 30 to 925 days). Cats that underwent only 1 surgery prior to radiotherapy had a lower recurrence rate than did cats that underwent > 1 surgery and had a significantly longer disease-free interval. Survival time and disease-free interval decreased as time between surgery and the start of radiotherapy increased. Cats that developed metastases had significantly shorter survival times and disease-free intervals than did cats that did not develop metastases. Castrated male cats had a significantly shorter survival time than did spayed female cats. Cats with larger tumors prior to the first surgery had shorter survival times. Twenty-six cats received chemotherapy in addition to surgery and radiotherapy. Whether cats received chemotherapy was not associated with recurrence rate, metastasis rate, or survival time. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that excision followed by electron beam irradiation may be beneficial for treatment of cats with vaccine-associated sarcomas. Extent of excision prior to radiotherapy did not seem to be associated with recurrence rate.     

Prognosis for presumed feline vaccine-associated sarcoma after excision: 61 cases (1986-1996)

OBJECTIVE: To evaluate time to first recurrence (TFR) and overall survival in cats with presumed vaccine-associated sarcomas (VAS) treated with excision. DESIGN: Retrospective study. ANIMALS: 61 cats with presumed VAS. PROCEDURE: Medical records of cats that received excision as the only initial treatment for presumed VAS were reviewed to evaluate prognosis. Overall survival curves and TFR were determined. RESULTS: Median TFR was 94 days. Median TFR for tumors treated with excision performed at a referral institution (274 days) was significantly longer than that for tumors excised by a referring veterinarian (66 days). Radical first excision yielded significantly longer median TFR (325 days) than did marginal first excision (79 days). Cats with tumors located on the limbs had longer median TFR (325 days) than cats with tumors located in other sites (66 days). Median overall survival time was 576 days. Significant differences in survival times between groups were not detected. Few cats (13.8%) receiving only surgical treatment had long-term (> 2 years) survival. CONCLUSIONS AND CLINICAL RELEVANCE: Radical first excision of presumed VAS is essential for extended TFR. Current recommendations for vaccination of the distal portions of the extremities are appropriate, because this practice permits radical excision of tumors (amputation) that develop at vaccination sites; however, surgery alone is seldom curative.     

Surgery alone versus surgery and doxorubicin for the treatment of feline injection-site sarcomas: a report on 69 cases

Sixty-nine cats were treated for injection-site sarcomas at the Veterinary Teaching Hospital of Grugliasco, Turin (Italy). The animals were divided into two subgroups: those subjected to four doxorubicin cycles combined with radical surgical excision 10 days after the second chemotherapy cycle (group A, 49 cats) or those treated with surgery alone (group B, 20 cats). Each cat was monitored for lung metastasis and local recurrence. In group A, 28 cats were alive at the end of the follow-up period. In this group, the recurrence rate was 40.8% while lung metastasis occurred in 12% of cats. In group B, eight animals were alive at the end of the follow-up period, while the rates of recurrence and metastasis were 35% and 10%. Neither the median disease-free interval nor the median overall survival was reached in either group. Moreover, there were no statistically significant differences between the two groups.     

Radiation treatment for incompletely resected soft-tissue sarcomas in dogs

OBJECTIVE: To evaluate efficacy of radiation for treatment of incompletely resected soft-tissue sarcomas in dogs. DESIGN: Prospective serial study. ANIMALS: 48 dogs with soft-tissue sarcomas. PROCEDURE: Tumors were resected to < 3 cm3 prior to radiation. Tumors were treated on alternate days (three 3-Gy fractions/wk) until 21 fractions had been administered. Cobalt 60 radiation was used for all treatments. RESULTS: Five-year survival rate was 76%, and survival rate was not different among tumor types or locations. Four (8%) dogs developed metastases. Eight (17%) dogs had tumor recurrence after radiation. Development of metastases and local recurrence were significantly associated with reduced survival rate. Median survival time in dogs that developed metastases was 250 days. Median disease-free interval for all dogs was 1,082 days. Median time to recurrence was 700 days. Dogs that developed recurrence after a prolonged period responded well to a second surgery. Acute radiation toxicosis was minimal; osteosarcoma developed at the radiation site in 1 dog. CONCLUSIONS AND CLINICAL RELEVANCE: An excellent long-term survival rate may be achieved by treating soft-tissue sarcomas in dogs with resection followed by radiation. Amputation is not necessary for long-term control of soft-tissue sarcomas in limbs. Development of metastases and recurrence of local tumors after radiation treatment are associated with decreased survival rate. Acute and delayed radiation toxicosis was minimal with the protocol used in this study.     

Evaluation of radiotherapy alone or in combination with doxorubicin chemotherapy for the treatment of cats with incompletely excised soft tissue sarcomas: 71 cases (1989-1999)

OBJECTIVE: To determine whether the addition of doxorubicin chemotherapy affected the outcome of cats with incompletely excised, nonvisceral soft tissue sarcomas undergoing postoperative radiotherapy. DESIGN: Retrospective case series. ANIMALS: 71 cats. PROCEDURES: Medical records were reviewed for clinically relevant data on cats that underwent postoperative radiotherapy for treatment of incompletely excised soft tissue sarcomas with or without concurrent doxorubicin chemotherapy. Radiotherapy was performed on an alternate-day schedule, with a total dose of 58.8 to 63 Gy delivered in 21 fractions. Doxorubicin was administered every 21 days for 3 to 5 cycles. Follow-up information was obtained by means of physical examination or through telephone conversations with refer-ring veterinarians or owners. RESULTS: Median disease-free interval with concurrent radiotherapy and doxorubicin chemotherapy (15.4 months; range, 2.4 to 44.9 months) was significantly longer than median disease-free interval with radiotherapy alone (5.7 months; range, 1.0 to 50.8 months). However, survival time was not significantly different between groups. CONCLUSION AND CLINICAL RELEVANCE: Results suggested that doxorubicin chemotherapy may play a role in extending the disease-free interval in cats undergoing radiotherapy for treatment of incompletely excised soft tissue sarcomas.     

Combined doxorubicin and cyclophosphamide chemotherapy for nonresectable feline fibrosarcoma

A retrospective evaluation was performed on 12 cats with nonresectable, histopathologically confirmed fibrosarcomas that were treated with doxorubicin and cyclophosphamide chemotherapy. All of the tumors were located in sites potentially used for vaccination. Six cats had a greater than 50% decrease in gross tumor burden. However, the responses were not durable, with a median response duration of 125 days. All cats developed progressive disease. When animals that received other treatments after doxorubicin-based chemotherapy were eliminated from the analysis, median survival time was significantly longer for cats that responded to chemotherapy compared with the median survival time for nonresponders (242 and 83 days, respectively). These findings may serve as a basis for further evaluating the role of chemotherapy in the treatment of vaccine-associated sarcomas.     

Evaluation of outcome associated with subcutaneous and intramuscular hemangiosarcoma treated with adjuvant doxorubicin in dogs: 21 cases (2001-2006)

OBJECTIVE: To evaluate outcome associated with subcutaneous and intramuscular hemangiosarcomas treated with adjuvant doxorubicin in dogs. DESIGN: Retrospective case series. ANIMALS: 21 dogs. PROCEDURES: Records of dogs with histologically confirmed hemangiosarcoma, no detectable metastasis at initial evaluation, and adequate local tumor control were included. Age, sex, number of treatments, treatment interval, radiation therapy, and concurrent use of cyclophosphamide or deracoxib were evaluated for associations with disease-free interval (DFI) or survival time. Three to 6 cycles of doxorubicin were planned. Disease-free interval was defined as time of definitive surgery to time of local recurrence, metastasis, or both. Survival time was defined as the beginning of the DFI to time of death. RESULTS: 17 tumors were subcutaneous, and 4 were intramuscular. Median age was 9 years. Median weight was 31.1 kg (68.4 lb). Five dogs received adjuvant radiation therapy. Median DFI for subcutaneous tumors was 1,553 days (95% confidence interval [CI], 469 days to not estimable). Median DFI for intramuscular tumors was 265.5 days (95% CI, 123 to 301 days). Median survival time for subcutaneous tumors was 1,189 days (95% CI, 596 days to not estimable). Median survival time for intramuscular tumors was 272.5 days (95% CI, 123 to 355 days). For dogs with subcutaneous tumors, younger age (< 9 years) was associated with longer DFI and survival time. Dogs with subcutaneous tumors that did not receive radiation therapy had longer DFI. CONCLUSIONS AND CLINICAL RELEVANCE: Dogs with subcutaneous hemangiosarcoma had a more favorable outcome, compared with dogs with intramuscular hemangiosarcoma, when treated with adequate local control and adjuvant doxorubicin.     

Outcome following surgical removal of nonvisceral soft tissue sarcomas in cats: 42 cases (1992-2000)

OBJECTIVE: To identify factors associated with outcome of cats with nonvisceral soft tissue sarcomas treated with surgery alone. DESIGN: Retrospective study. ANIMALS: 42 cats. PROCEDURE: Medical records were reviewed for clinically relevant data, and histologic samples were examined. Follow-up information was obtained by means of physical examination or through telephone conversations with referring veterinarians and owners. The Kaplan-Meier method was used to construct survival curves. RESULTS: Median survival time was 608 days (range, 85 to 2,291 days), although 24 cats were still alive at the time of the study. Tumor size (ie, diameter) and histologic type were significantly associated with survival time. Median survival time was significantly longer in cats with tumors that were < 2 cm in diameter, compared with cats in which tumors were > 2 cm. Median survival times for cats with a fibrosarcoma or nerve sheath tumor were significantly longer than median time for cats with a malignant fibrous histiocytoma. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that tumor size and type are significantly associated with survival time in cats with nonvisceral soft tissue tumors.     

RADIOTHERAPY AND SURGERY FOR FELINE SOFT TISSUE SARCOMA

Medical records for 79 cats with soft tissue sarcomas treated with preoperative or postoperative curative intent radiation therapy between August 1994 and February 2004 were reviewed. The purpose was to assess the effectiveness of preoperative and postoperative radiation therapy, and to determine the association of patient and radiation treatment variables with survival. Gender, age, weight, anatomic tumor site, packed cell volume (PCV), computerized vs. manual treatment planning, radiation field length, preoperative vs. postoperative irradiation, total radiation dose, and biologically effective dose (BED) were assessed as prognostic factors for survival. Fifty-six of 79 (71%) of cats were anemic within 2 weeks before or during radiation treatment. The median survival was 520 days for all cats, with a 1-year survival rate of 61.6%, and a 2-year survival rate of 41.6%. Only timing of radiation therapy relative to surgery and presence of a moderate or severe anemia were significantly related to survival. The median survival was 310 days for cats treated with preoperative radiation therapy, and 705 days for cats treated with postoperative radiation therapy ( P =0.03). The median survival was 308 days for cats with a PCV<25%, and 760 days for cats with a PCV≥25% ( P =0.017). Radiation therapy in combination with surgery results in relatively long-term survival in cats with soft tissue sarcomas. Anemia is common in cats undergoing radiation therapy for soft tissue sarcomas, and is associated with decreased survival.     

Establishment of two vaccine-associated feline sarcoma cell lines and determination of in vitro chemosensitivity to doxorubicin and mitoxantrone

OBJECTIVE: To establish 2 vaccine-associated feline sarcoma (VAFS) cell lines and to determine their in vitro sensitivity to the chemotherapeutic agents doxorubicin and mitoxantrone. SAMPLE POPULATION: Tumor specimens collected from 2 cats undergoing surgery for removal of vaccine-associated sarcomas. PROCEDURES: Tumor specimens were minced and treated with trypsin under aseptic conditions to obtain single-cell suspensions, which were then cultured in vitro in medium supplemented with 5% heat-inactivated fetal bovine serum. Growth rates and sensitivity after 24 hours of exposure to various concentrations (0.1 to 100 microg/ml) of doxorubicin and mitoxantrone were assessed for each cell line. Survival of cells was estimated 3 days after exposure to the 2 agents, and the concentration of each drug that resulted in a 50% reduction in the number of viable cells (IC50) was calculated. RESULTS: Two tumor-derived cell lines (FSA and FSB) were successfully established and determined to be sensitive to doxorubicin and mitoxantrone. Under the conditions tested, the IC50 of doxorubicin were 0.6 and 1.5 microg/ml for cell lines FSB and FSA, respectively. The IC50 of mitoxantrone was 0.4 microg/ml for both cell lines. CONCLUSIONS AND CLINICAL RELEVANCE: The establishment of VAFS cell lines provides a tool for the in vitro screening of antitumor drugs. Doxorubicin and mitoxantrone were effective in decreasing the number of viable cells in the 2 cell lines tested. Both of these anthracycline antibiotics have been used to treat various neoplasias in cats, and their efficacy for adjuvant treatment of vaccine-associated sarcomas should be further evaluated.     

Results of excision of thymoma in cats and dogs: 20 cases (1984-2005)

OBJECTIVE: To provide long-term follow-up information for a series of dogs and cats with invasive and noninvasive thymomas treated by excision alone. DESIGN: Retrospective case series. ANIMALS: 9 cats and 11 dogs with thymoma. PROCEDURES: Medical records were reviewed. The following factors were analyzed for their effect on prognosis: age of dog or cat, invasiveness of the tumor, percentage of lymphocytes in the mass (percentage lymphocyte composition) on histologic evaluation, and mitotic index of the mass. RESULTS: All patients were treated with excision of the tumor alone. Median overall survival time for the cats was 1,825 days, with a 1-year survival rate of 89% and a 3-year survival rate of 74%. Median overall survival time for the dogs was 790 days, with a 1-year survival rate of 64% and a 3-year survival rate of 42%. Recurrence of thymoma was observed in 2 cats and 1 dog, and a second surgery was performed in each, with subsequent survival times of 5, 3, and 4 years following the first surgery. Percentage lymphocyte composition of the mass was the only factor that was significantly correlated with survival time; animals with a high percentage of lymphocytes lived longer. CONCLUSIONS AND CLINICAL RELEVANCE: Results of this study indicated that most cats and dogs with thymomas did well after excision. Even cats and dogs with invasive masses that survived the surgery and the few cats and dogs with recurrent thymomas or paraneoplastic syndromes had a good long-term outcome. Excision should be considered an effective treatment option for dogs and cats with thymomas.     

CONCOMITANT LIPOSOMAL DOXORUBICIN AND DAILY PALLIATIVE RADIOTHERAPY IN ADVANCED FELINE SOFT TISSUE SARCOMAS

Local recurrence of feline soft tissue sarcomas is common despite aggressive treatment. Liposomal doxorubicin might serve as a depot radiosensitizer if administered concomitantly with daily radiotherapy and thus improve tumor control. In this pilot study, the feasibility of concomitant liposomal radiochemotherapy was evaluated in a palliative setting in 10 cats with advanced soft tissue sarcomas. Cats were treated with median number of 5 (range 5–7) daily fractions of radiotherapy and a median total dose of 20 Gy (range 20–31.5 Gy). One dose of liposomal doxorubicin was administered at the beginning of radiotherapy. Seven cats received further free or liposomal doxorubicin after completion of the liposomal doxorubicin/radiation protocol. Seven of the treated 10 cats (70%) achieved a partial (n=5) or complete (n=2) response with a median response duration of 237 days. The median progression free interval in all 10 cats was 117 days and the median overall survival time was 324 days. Concomitant liposomal radiochemotherapy was tolerated well in nine cats, one cat experienced temporary anorexia. Although the number of patients is too small to make definitive conclusions, results appear promising enough to investigate the role of liposomal doxorubicin as a radiosensitizer further.     

Surgical decompression,with or without adjunctive therapy,for palliative treatment of primary vertebral osteosarcoma in dogs

Vertebral osteosarcoma (OSA) is the most common primary vertebral tumor in dogs, however studies examining the survival time after surgical decompression of these tumors are limited. There is also limited information regarding the benefit of adjunctive treatments such as radiation therapy or chemotherapy in these patients. The goal of this study was to determine survival time of dogs with primary vertebral OSA after palliative decompressive surgery alone and combined with radiation therapy and/or chemotherapy. Records from 22 client‐owned dogs diagnosed with primary vertebral OSA and treated with decompressive surgery were collected retrospectively from eight referral institutions. Survival time was assessed for dogs treated with surgery alone as well as dogs who received adjunctive radiation therapy and/or chemotherapy. Median survival time in the 12 dogs treated with surgery alone was 42 days (range: 3‐1333 days). The three dogs treated with surgery and chemotherapy had a median survival time of 82 days (range: 56‐305 days). Only one dog was treated with surgery and radiation therapy; this dog survived 101 days. Six dogs were treated with surgery, radiation therapy and chemotherapy; these dogs had a median survival time of 261 days (range: 223‐653 days). Cause of death in all cases that survived the initial postoperative period was euthanasia secondary to confirmed or suspected tumor regrowth. The results of this study suggest that definitive radiation therapy, possibly combined with concurrent chemotherapy, significantly improves survival in dogs treated with palliative decompressive surgery for vertebral OSA and should be the treatment of choice in selected cases.     

Treatment of vascular and soft-tissue sarcomas in dogs using an alternating protocol of ifosfamide and doxorubicin

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 µL^?1) after treatment with ifosfamide and one dog had grade 3 neutropenia (500–1000 µL^?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.     

Evaluation of treatment with doxorubicin and piroxicam or doxorubicin alone for multicentric lymphoma in dogs

OBJECTIVE: To evaluate the antitumor and toxic effects of treatment with doxorubicin combined with piroxicam or doxorubicin alone for multicentric lymphoma in dogs. DESIGN: Nonrandomized clinical trial. ANIMALS: 75 dogs with multicentric lymphoma. PROCEDURE: 33 dogs were treated with doxorubicin (30 mg/m2, IV, q 21 d, for 3 doses) and piroxicam (0.3 mg/kg [0.14 mg/lb], PO, q 24 h); results were compared with a historical control group of 42 dogs treated with doxorubicin (30 mg/M2, IV, q 21 d, for 3 doses) alone. Results-The percentages of dogs that had remission with doxorubicin-piroxicam treatment (79%) or doxorubicin treatment alone (74%) were not significantly different. Median duration of first remission was 130 days with doxorubicin-piroxicam and 147 days with doxorubicin alone; these values were not significantly different. Severe toxicosis was observed in 22% of dogs treated with doxorubicin-piroxicam and 17% of dogs treated with doxorubicin alone. CONCLUSIONS AND CLINICAL RELEVANCE: Both treatment protocols were efficacious and well tolerated. The doxorubicin-piroxicam treatment was no more effective regarding response rate, remission duration, or survival duration, compared with the control group treated with doxorubicin alone.     

Outcome of dogs with high-grade soft tissue sarcomas treated with and without adjuvant doxorubicin chemotherapy: 39 cases (1996-2004)

OBJECTIVE: To examine the effect of adjuvant doxorubicin chemotherapy on outcome in dogs with high-grade (grade 3) soft tissue sarcomas (HGSTSs). DESIGN: Retrospective case series. ANIMALS: 39 dogs. PROCEDURES: Medical records of dogs with HGSTSs were reviewed. Dogs treated with surgery alone or receiving single-agent doxorubicin chemotherapy postoperatively were included in the study. Owners and referring veterinarians were contacted for follow-up information. Slides from histologic sections were reviewed to confirm the diagnosis of HGSTSs. Cases in which follow-up examination was not performed and radiation therapy or chemotherapy other than doxorubicin was administered were excluded. RESULTS: 39 dogs met inclusion criteria. Twenty-one dogs received adjuvant doxorubicin. Tumor-, patient-, and treatment-related variables were not significantly associated with measured outcomes including local, metastatic, and overall disease-free intervals as well as survival time. Overall median disease-free interval was 724 days with a median survival time of 856 days for all dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Adjuvant doxorubicin-based chemotherapy did not benefit this population of dogs with HGSTSs. Outcome for visceral HGSTSs was similar to that of nonvisceral HGSTSs in these cases.     

Combination chemotherapy in feline lymphoma: treatment outcome, tolerability, and duration in 23 cats

BACKGROUND: Different chemotherapy regimes have been described for feline lymphoma with varying outcomes. HYPOTHESIS: In cats with lymphoma, a long-term, multiagent chemotherapy protocol will be effective and carry acceptable toxicity. ANIMALS: Twenty-three cats with histologically or cytologically confirmed diagnosis of lymphoma. METHODS: Prospective, single-arm clinical trial in which cats were treated with a chemotherapy protocol consisting of a cyclic combination of l-asparaginase, vincristine, cyclophosphamide, doxorubicin, methotrexate, and prednisolone with a planned total treatment time of 122 weeks. RESULTS: Complete remission (CR) rate was 74% (n = 17). Fourteen percent of cats attained partial remission (PR). Median duration of first CR was 264 days (range, 45-2,485 days). Six-month, 1-, and 2-5-year remission rates were 75, 50, and 34%, respectively. Duration of PR ranged between 23 and 63 days. Median survival in cats with CR was 296 days (range, 50-2,520 days). Six-month, 1-, 2-, and 3-5-year survival rates in cats with CR were 82, 47, 34, and 27%, respectively. Survival of cats achieving PR ranged between 38 and 120 days. Of the analyzed variables, only anatomical location had a significant influence on remission duration (P=.022). Actual median treatment time in cats with CR was 128 days (18 weeks). Hematologic and gastrointestinal toxicosis was infrequent and mostly low grade. CONCLUSIONS AND CLINICAL IMPORTANCE: In this population of cats with lymphoma, chemotherapy was effective. With infrequent and mostly low-grade toxicosis, tolerability of the protocol may be considered good.     

Orthovoltage radiation and weekly low dose of doxorubicin for the treatment of incompletely excised soft-tissue sarcomas in 39 dogs

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.     

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.     

Murine xenograft model demonstrates significant radio-sensitising effect of liposomal doxorubicin in a combination therapy for Feline Injection Site Sarcoma

Therapy of cats suffering from feline injection site sarcomas (FISS) is still a challenging problem, as the recurrence rate after surgery is up to 70%. Four FISS-derived primary tumour cell lines and corresponding xenograft tumour mouse models were established to evaluate the efficacy of a concomitant chemo-/radiation therapy with doxorubicin. In vitro, strongly depending upon the timing of administration, pre-treatment with 0.25 µmol doxorubicin resulted in a significant enhancement of radiation-induced (3.5 Gy) tumour cell death. This result was confirmed in vivo, where only the combined chemo-/radiation therapy resulted in a significant reduction in tumour growth compared to the respective mono-therapies with either doxorubicin or radiation. These results support the use of the concomitant chemo-/radiation therapy for adjuvant treatment of FISS, particularly in advanced or recurrent disease where surgery alone is no longer feasible.