Evaluation of adjuvant carboplatin chemotherapy in the management of surgically excised anal sac apocrine gland adenocarcinoma in dogs

There is no widely accepted standard of care for canine anal sac apocrine gland adenocarcinoma (ASAGAC). Surgery alone is inadequate in many cases, but the benefit of adjuvant chemotherapy is not well established. The primary objective of this retrospective study was to evaluate the role of carboplatin chemotherapy in the post‐operative management of ASAGAC. Seventy‐four dogs with naturally occurring ASAGAC underwent surgery. Forty‐four dogs received adjuvant carboplatin and 30 did not. Median overall survival (OS) was 703 days. Median time to progression (TTP) was 384 days. Only primary tumour size and lymph node metastasis at diagnosis significantly impacted the outcome. Differences in OS and TTP, between the dogs that received adjuvant carboplatin and those that did not, failed to reach statistical significance. Treatment of progressive disease, whilst not limited to chemotherapy, significantly prolonged the survival. This study shows that adjuvant carboplatin chemotherapy is well tolerated and may have a role in the management of dogs with ASAGAC.     

Long‐term survival in dogs with localized histiocytic sarcoma treated with CCNU as an adjuvant to local therapy*

Histiocytic sarcoma (HS) is associated with a poor prognosis owing to the presence of metastasis at the time of diagnosis in most dogs. Improved outcome has been reported in several dogs with localized HS following local therapy, however, distant metastasis occurs in 70–91% of dogs suggesting that adjuvant systemic therapy is necessary. The purpose of this retrospective study was to describe clinical characteristics and outcome in dogs with localized HS treated with aggressive local therapy plus adjuvant CCNU chemotherapy. Data from 16 dogs were evaluated. The median disease‐free interval was 243 days. Two dogs had local recurrence and eight dogs developed metastatic disease with a median time to relapse of 201 days in these 10 dogs. The median survival time for all 16 dogs was 568 days. These results support the recommendation for aggressive local therapy combined with adjuvant CCNU chemotherapy in dogs with localized HS.     

The effects of cancer and cancer therapies on wound healing

Based on experimental evidence in rodents, most of the antineoplastic agents will affect wound healing. With most of the agents, this impairment is not sufficient to produce increased morbidity based on the clinical reports in humans. Radiation therapy appears to inhibit healing in both experimental animals and during clinical trials. In spite of this, it is reported that wounds in animals will heal when they are receiving radiation therapy after surgery. Based on the information presented here and experience at the University of Missouri, the decision to use adjuvant therapy should depend on the surgery performed. With a single incision that had no increased tension, there should be no hesitation to use adjuvant therapy. If removal of the tumor required reconstructive surgery, no radiation or chemotherapy should be used until the wound has healed.     

Timely adjuvant chemotherapy improves outcome in dogs with non-metastatic splenic hemangiosarcoma undergoing splenectomy

Timely delivery of adjuvant chemotherapy has been shown to be advantageous in many human cancers and canine osteosarcoma. Adjuvant chemotherapy has been shown to improve outcome for canine splenic hemangiosarcoma. The aim of this retrospective study was to investigate whether timely adjuvant chemotherapy administration resulted in better outcome in dogs with non-metastatic splenic hemangiosarcoma undergoing splenectomy. Medical records were searched for dogs with non-metastatic, splenic hemangiosarcoma that received splenectomy and adjuvant chemotherapy. The number of days from surgery to the first chemotherapy dose (StoC) was evaluated to identify the cut-off value associated with the best survival advantage. StoC and other possible prognostic factors were tested for influence on time to metastasis (TTM) and overall survival (OS). Seventy dogs were included. Median StoC was 20 days (range: 4–70). The time interval associated with the greatest survival benefit was 21 days. Median TTM and OS of dogs with StoC ≤ 21 days were significantly longer than those with StoC >21 days (TTM: 163 vs. 118 days, p = .001; OS: 238 vs. 146 days, p < .001). On multivariable analysis, StoC >21 days was the only variable significantly associated with increased risk of tumour progression (HR 2.1, p = .010) and death (HR 2.3; p = .008). Starting adjuvant chemotherapy within 21 days of surgery may be associated with a survival benefit in dogs with non-metastatic splenic hemangiosarcoma, possibly due to the early targeting of newly recruited metastatic cells after surgery.     

Laboratory trials with inactivated vaccines against Escherichia coli (O2:K1) infection in fowls.

Laboratory trials were carried out with an O2:K1 vaccine prepared with either the Freund's complete or incomplete adjuvant. Both types of vaccine administered subcutaneously were highly effective against a challenge with the vaccine strain within three to four weeks after vaccination at two to three weeks of age. The complete adjuvant vaccine was more effective than the incomplete adjuvant vaccine when administered to chickens of an earlier age, and in the rate of development and duration of immunity. The efficacy of both vaccines was unimpaired by their incorporation with the Newcastle disease oil adjuvant (inactivated) vaccine (Newcadin). The use of an oil adjuvant vaccine was not found to affect the rate of growth adversely or to produce any other reaction prejudicial to its commerical application. The efficacy of the vaccines was unimpaired by their incorporation with Newcastle disease oil adjuvant (inactivated) vaccine (Newcadin) thus demonstrating the possibility of producing a combined Escherichia coli/Newcastle disease virus vaccine.     

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.     

Toxicity and efficacy of a novel doxorubicin and carboplatin chemotherapy protocol for the treatment of canine appendicular osteosarcoma following limb amputation

Objective To evaluate the safety and efficacy of a novel doxorubicin and carboplatin chemotherapy protocol for the treatment of dogs with appendicular osteosarcoma following limb amputation. Design Retrospective study. Procedure Dogs diagnosed with appendicular osteosarcoma, with no evidence of metastatic disease, treated with amputation and adjuvant chemotherapy consisting of two doses of doxorubicin given 14 days apart, followed by four doses of carboplatin at 3‐weekly intervals between September 2003 and December 2009 were identified from the medical records of Perth Veterinary Oncology. Haematological and gastrointestinal toxicities were assessed based on information in the medical records and recorded complete blood count results. The efficacy of the protocol was assessed by determining the median disease‐free interval (DFI) and overall survival time (OST) using the Kaplan‐Meier product‐limit method. Results In total, 33 dogs met the inclusion criteria. The median DFI was 231.5 days and the median OST was 247 days. With regard to haematological toxicity, 56% of dogs had a grade 1–2 neutropenia recorded as their highest marrow toxicity and 9% of dogs experienced a grade 3–4 neutropenia, all subsequent to doxorubicin administration. The highest gastrointestinal toxicity was grade 1–2 in 15 dogs (47%) and 5 dogs (16%) experienced grade 3–4 gastrointestinal toxicity. Conclusion This chemotherapy protocol did not result in a longer time to disease recurrence or OST in this population of dogs. Dual‐agent protocols have failed to improve survival times and therefore we conclude that a single‐agent protocol using carboplatin may be equally effective with less toxicity.     

Clinical outcome in 23 dogs with exocrine pancreatic carcinoma

Exocrine pancreatic carcinoma is uncommon in the dog and the veterinary literature surrounding the disease is minimal. Twenty‐three cases of canine exocrine pancreatic carcinoma were reviewed in a retrospective manner to obtain information on clinical presentation, behaviour and survival associated with the disease. Presenting clinical signs were nonspecific and included anorexia, lethargy, vomiting and abdominal pain. The overall median survival time was only 1 day but was confounded by the large number of dogs that were euthanized shortly after diagnosis. Metastatic disease was detected in 78% of cases at the time of diagnosis, attesting to the aggressive nature of the disease. Neither lymph node metastasis, tumour size nor tumour location had an impact on overall survival. Only one patient was a previous diabetic who is contrary to reports of the disease in people and felines. This retrospective study reaffirms the need for early detection measures to optimize disease control. However, the benefits of therapy with surgery or radiation and adjuvant chemotherapy remain to be elucidated in dogs with exocrine pancreatic carcinoma.     

Immunization trials with virus-free antigens against Marek''s disease

Additional immunization trials were performed to study the immunogenicity of the purified skin antigen of Marek's disease virus which was inoculated, together with Freud's complete adjuvant, into one-day-old chicks. As compared to non-vaccinated chickens and also to chickens vaccinated by herpesvirus turkey (which reduced the mortality by 45.54%) the purified skin antigen reduced the mortality by 69.50%.

In the case of immunization with protein extract from the lymphoblastoid cell line of Marek's disease lymphomes mixed with natural dsRNA showed 38.99% reduction of mortality. DEAE-dextran which had exerted an adjuvant effect in our previous report did not by itself reduce mortality caused by Marek's disease.

Groups of chickens vaccinated with the turkey herpesvirus with protein extract mixed with dsRNA, and a group of chickens inoculated with 0.04 g.ml⁻¹ DEAE-dextran, had a higher whole complement activity in pooled serum from 107 days after challenge than chickens free of Marek's disease.     

Splenic marginal zone lymphoma in 5 dogs (2001-2008)

Background: Splenic marginal zone lymphomas (MZL) in dogs arise from the marginal zone of B‐cell follicles and can progress slowly. Objectives: To describe clinical features, treatment, and outcome of dogs with splenic MZL. Animals: Five dogs with naturally occurring MZL. Methods: Clinical, laboratory, and follow‐up data were retrospectively reviewed. Diagnosis was based on clinical, histopathological, and immunophenotypic features. Results: All dogs had stage IV disease; among them, 2 were symptomatic (substage “b”) because of splenic rupture. Four dogs underwent splenectomy and adjuvant doxorubicin, and 1 dog underwent surgery only. Three out of the 4 dogs treated with surgery and chemotherapy died of causes unrelated to lymphoma, after 760, 939, and 1,825 days, whereas the remaining dog was alive and in complete remission after 445 days. The dog not receiving any adjuvant treatment had recurrence of the tumor after 180 days. Conclusions and Clinical Importance: Splenic MZL appears indolent and can benefit from splenectomy, with or without systemic chemotherapy.     

Mathematical models of the population biology of Ostertagia ostertagi and Teladorsagia circumcincta, and the economic evaluation of disease control strategies

The construction and use of mathematical models of the population biology of Ostertagia ostertagi and Teladorsagia circumcincta is discussed. Simulated field trials implemented by deterministic mathematical models currently share with actual field trials the disadvantage that they convey no information concerning the risk associated with the net return demonstrated by the trial. This has important implications when it is necessary to rank disease control strategies in order of usefulness.     

Whole-Body Hyperthermia

Whole-body hyperthermia is the controlled elevation of systemic temperature for therapeutic purposes. Historically, this treatment has been used for symptomatic control of many diseases. Recently, the potential therapeutic benefit of whole-body hyperthermia in the management of neoplastic disease has been investigated vigorously. The rationale for improved tumor control is based on heat-induced enhancement of the antineoplastic effects of radiation and chemotherapy. Although the complex biologic interaction of heat and radiation has been studied for many years, chemotherapy combined with hyperthermia has been studied less thoroughly. Despite a lack of adequate long-term laboratory and clinical investigation, use of whole-body hyperthermia with chemotherapy and radiotherapy is a logical and potentially powerful therapeutic strategy for neoplasia. Relevant issues regarding the application of whole-body hyperthermia with more traditional modes of therapy are being studied in preliminary clinical trials involving dogs and humans. Identification of optimal timing and sequencing of adjunctive therapy, proper cytotoxic drug application, methods to further minimize toxicity, and heat-sensitive tumor types will lead to expanded clinical use of whole-body hyperthermia. The historical development, clinical rationale, and application of whole-body hyperthermia for the control of disseminated or refractory neoplasia in humans and dogs is reviewed.     

Chemotherapy Versus Chemotherapy Plus Radiotherapy in the Treatment of Tonsillar Squamous Cell Carcinoma in the Dog

The effect of adjuvant chemotherapy and combined chemotherapy and radiotherapy in 22 dogs with advanced canine tonsillar carcinoma (World Health Organization [WHO], T2-3 primary tumor with infiltration into surrounding tissues) was evaluated. There were four treatment groups of at least five dogs each. Combinations of chemotherapeutic drugs reported to have activity against squamous cell carcinoma in humans and dogs (doxorubicin, cisplatin, vinblastine, and cyclophosphamide) were administered after tonsillectomy. Radiation therapy (orthovoltage type, external beam) was combined with chemotherapy in one treatment group. The dogs that had combination radiation therapy and chemotherapy had higher response rates and significantly longer survival times. However, most dogs died of progression of disease.     

Neoadjuvant chemoradiotherapy and surgery as treatment for oral maxillary squamous cell carcinoma in a dog

A gingival maxillary squamous cell carcinoma was diagnosed in a 12-year-old male Yorkshire Terrier. After a complete diagnostic work-up, including a computed tomography scan, the tumour was staged as T3bN1aM0 and considered non-resectable at presentation. The combination of neoadjuvant megavoltage radiotherapy and neoadjuvant and adjuvant chemotherapy with carboplatin and doxorubicin decreased the size of the tumour, allowing for surgery. The dog was free from local disease for 421 days after which it was euthanased at the owners' request.     

Intraperitoneal injection of an adjuvant for the prevention of post-weaning diarrhoea and oedema disease in piglets: A field study

Shortly before weaning, piglets were intraperitoneally injected with a stable water-in-oil emulsion serving as an adjuvant without any added antigens. The aim of this treatment was to potentiate the immune response to naturally occurring antigens of pathogenic organisms in the gut, and thereby to prevent post-weaning diarrhoea and oedema disease. Experiments were done on seven farms and comprised more than 7,000 piglets. Results indicate a positive effect of the intraperitoneal adjuvant injection on mortality rates, viz. average mortality rate after weaning decreased from circa 12% to 2%. Moreover, the need for antibiotic treatment declined sharply. A statistically significant positive effect of adjuvant treatment was shown by adopting experimental schemes involving alternate treatment with adjuvant and physiological saline, or adjuvant treatment andno treatment at all. Possible side effects and prospects for the future of this alternative vaccination principle are discussed.     

Multilobular osteochondrosarcoma of the canine skull: 16 cases (1978-1988)

The medical records of 12 dogs with multilobular osteochondrosarcoma (MLO) and examined at the Veterinary Teaching Hospital, Colorado State University from August 1979 to January 1987 were reviewed. Medical records of 1 dog with MLO and 3 dogs with MLO examined at the Ontario Veterinary College, University of Guelph and the Veterinary Medical Teaching Hospital, University of California, Davis, respectively, were also reviewed and included in the study. The mean age of affected dogs was 7.5 years, a single breed did not appear to be overrepresented, and males were affected as frequently as were females. All of the primary lesions affected either the mandible, maxilla, or cranium. Excision was the only treatment in 11 dogs, 2 dogs had radiotherapy in addition to excision, and 1 dog had radiotherapy and chemotherapy after excision. Twelve treated dogs had follow-up information available. Of the 12 treated dogs, 7 (58%) had local recurrence, with median time to recurrence of 14 months. Seven dogs (58%) developed metastatic disease after treatment, with median time to metastasis of 14 months. The median disease-free interval was 12 months, and the median survival time was 21 months. Excision with histologically complete surgical margins appeared to offer good opportunity for long-term tumor control. The role of adjuvant chemotherapy and radiotherapy in the management of MLO remains unclear.     

Affinity of the alpha4-beta1 integrin-targeting peptide LLP2A to canine lymphoma

Lymphoma is an important disease in dogs and people, with similar biological characteristics. We tested the binding affinity of a peptidomimetic LLP2A, previously shown to bind the alpha4-beta1 integrin on human lymphoma cell lines, to lymphocytes of dogs with spontaneously occurring lymphoma. Fine needle aspirates of lymph nodes from 32 dogs with B-cell lymphoma and 7 dogs with T-cell lymphoma were evaluated using flow cytometry. For B cells, the lowest MFI levels were in unlabeled, non-neoplastic lymphocytes. The highest median fluorescent intensity (MFI) levels occurred in LLP2A-labeled lymphoma cells from dogs that had not received chemotherapy followed by labeled lymphoma cells from dogs that had received chemotherapy. The fluorescence profile of the T-cell samples was similar although many of the differences were not statistically significant, likely due to low sample number. Specifically, LLP2A-labeled T-cell lymphoma cells had a significantly higher MFI compared to unlabeled non-neoplastic lymphocytes. LLP2A affinity was not significantly different in unlabeled and labeled T-cell lymphoma cells, and labeled non-neoplastic lymphocytes. For both B and T cells, labeling with LLP2A tended to increase MFI in both normal and lymphoma cells. Lymphoma cells had higher mean MFI levels than non-neoplastic lymphocytes, and chemotherapy acted to decrease MFI. In summary, these data demonstrate that LLP2A has affinity to canine lymphoma cells and indicates expression of the alpha4-beta1 integrin on these cells. In fact, LLP2A preferentially binds neoplastic B-cells, suggesting that this small molecule may be of use in cross-species clinical trials of targeted therapeutics.     

Evaluation of Adjuvant Doxorubicin-Based Chemotherapy for the Treatment of Feline Mammary Carcinoma

Background: Feline mammary carcinomas (FMC) are locally invasive and highly metastatic tumors. Because of the high metastatic potential, patients often are treated with adjuvant doxorubicin-based chemotherapy, but little data exist to evaluate the effect of this strategy.
Hypothesis: Adjuvant doxorubicin-based chemotherapy improves outcome for FMC compared with surgery alone.
Animals: Cats with naturally occurring, biopsy-confirmed FMC treated with either surgery alone (Sx) or with surgery plus adjuvant doxorubicin-based chemotherapy (Sx + Chemo).
Methods: Retrospective cohort study. Clinical data were collected and compared to identify differences between groups. Outcome results were determined and compared. Prognostic factors for disease-free survival (DFS) and overall survival were evaluated.
Results: Seventy-three cats were evaluated, of which 37 were in the Sx group and 36 in the Sx + Chemo group. No differences in clinical data were found between Sx and Sx + Chemo groups. Median DFS times for the Sx and Sx + Chemo groups were 372 and 676 days, respectively ( P = .15) and median survival times (ST) were 1,406 and 848 days, respectively ( P = .78). For cats that underwent a unilateral radical mastectomy, ST was significantly longer for the Sx + Chemo compared with the Sx group (1,998 versus 414 days, respectively; P = .03).
Conclusions and Clinical Importance: This study did not find a benefit to adjuvant doxorubicin-based chemotherapy in cats with FMC. Additional studies are required to determine whether patient subgroups with negative prognostic factors may benefit from adjuvant chemotherapy.     

Survival times in dogs with right atrial hemangiosarcoma treated by means of surgical resection with or without adjuvant chemotherapy: 23 cases (1986-2000)

OBJECTIVE: To determine survival times in dogs with right atrial hemangiosarcoma treated by means of pericardectomy and tumor resection, with or without adjuvant chemotherapy, and identify complications associated with treatment. DESIGN: Retrospective study. ANIMALS: 23 dogs. PROCEDURE: Dogs were included only if the diagnosis was confirmed histologically. RESULTS: The most common initial complaints included acute collapse (8 [35%] dogs), anorexia or inappetence (8 [35%]), and lethargy (8 [35%]). The most common physical examination abnormalities included muffled heart sounds (12 [52%] dogs), tachycardia (7 [30%]), and weak pulses (7 [30%]). Postoperative complications developed in 12 (52%) dogs; however, most complications were minor. Twenty (87%) dogs were discharged from the hospital. Survival time was significantly longer in the 8 dogs that received adjuvant chemotherapy (mean, 164 days; median, 175 days) than in the 15 dogs that did not receive chemotherapy (mean, 46 days; median, 42 days). Dogs that received chemotherapy were significantly younger and had significantly lower WBC counts than did dogs that did not receive chemotherapy. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that in dogs with right atrial hemangiosarcoma, surgical resection of the tumor was associated with a low complication rate and complications that did arise typically were minor. In addition, use of adjuvant chemotherapy following resection was associated with significantly longer survival times, compared with resection alone.     

Continuous low-dose oral chemotherapy for adjuvant therapy of splenic hemangiosarcoma in dogs

BACKGROUND: Hemangiosarcoma (HSA) is a highly metastatic and often rapidly fatal tumor in dogs. At present, conventional adjuvant chemotherapy provides only a modest survival benefit for treated dogs. Continuous oral administration of low-dose chemotherapy (LDC) has been suggested as an alternative to conventional chemotherapy protocols. Therefore, we evaluated the safety and effectiveness of LDC using a combination of cyclophosphamide, etoposide, and piroxicam as adjuvant therapy for dogs with stage II HSA. HYPOTHESIS: We hypothesized that oral adjuvant therapy with LDC could be safely administered to dogs with HSA and that survival times would be comparable to those attained with conventional doxorubicin (DOX) chemotherapy. ANIMALS: Nine dogs with stage II splenic HSA were enrolled in the LDC study. Treatment outcomes were also evaluated retrospectively for 24 dogs with stage II splenic HSA treated with DOX chemotherapy. METHODS: Nine dogs with stage II splenic HSA were treated with LDC over a 6-month period. Adverse effects and treatment outcomes were determined. The pharmacokinetics of orally administered etoposide were determined in 3 dogs. Overall survival times and disease-free intervals were compared between the 9 LDC-treated dogs and 24 DOX-treated dogs. RESULTS: Dogs treated with LDC did not develop severe adverse effects, and long-term treatment over 6 months was well-tolerated. Oral administration of etoposide resulted in detectable plasma concentrations that peaked between 30 and 60 minutes after dosing. Both the median overall survival time and the median disease-free interval in dogs treated with LDC were 178 days. By comparison, the overall survival time and disease-free interval in dogs treated with DOX were 133 and 126 days, respectively. CONCLUSIONS: Continuous orally administered LDC may be an effective alternative to conventional high-dose chemotherapy for adjuvant therapy of dogs with HSA.