The Etiology of Cancer

Vail, David M.; Thamm, Douglas H.; Liptak, Julias M.

doi:10.1016/b978-0-323-59496-7.00001-3

Cited by 69 publications

(183 citation statements)

References 307 publications

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“…These are also intensive protocols that require weekly to biweekly visits for 15 to 26 weeks. 1 , 2 , 3 , 4 , 5 Less intensive, often single‐agent protocols are also available as options, but tend to be associated with lower CR rates and shorter response durations. 17 , 18 , 19 Since the mechanism of action of RAB is different from standard chemotherapy drugs used to treat canine lymphoma, RAB could potentially be used in combination with other chemotherapy agents or integrated into CHOP‐based protocols to prolong remission durations and time to drug resistance.…”

Section: Discussionmentioning

confidence: 99%

“…Multicentric lymphoma is 1 of the most common cancers diagnosed in dogs, with an estimated annual incidence of 13 to 114 per 100 000 dogs at risk. 1 Multiagent chemotherapy protocols (eg, CHOP‐based protocols using a combination of cyclophosphamide, doxorubicin, vincristine, and prednisone) are the most common first‐line therapies used for dogs with lymphoma. These protocols have high remission rates (80%‐95%), but the majority of dogs will have relapse of the disease at some point either during or after treatment, with progression free intervals of approximately 5 to 7.5 months in most studies.…”

Section: Introductionmentioning

confidence: 99%

“…These protocols have high remission rates (80%‐95%), but the majority of dogs will have relapse of the disease at some point either during or after treatment, with progression free intervals of approximately 5 to 7.5 months in most studies. 1 , 2 , 3 , 4 , 5 There is an unmet need for novel anticancer agents for the treatment of lymphoma in dogs.…”

Section: Introductionmentioning

confidence: 99%

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Multicenter, randomized, double‐blinded, placebo‐controlled study of rabacfosadine in dogs with lymphoma

Weishaar

Wright

Rosenberg

et al. 2021

Veterinary Internal Medicne

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Background Rabacfosadine (RAB, Tanovea‐CA1) is a novel chemotherapy agent conditionally approved for the treatment of lymphoma in dogs. Hypothesis/Objectives To determine the efficacy and safety of RAB in dogs with lymphoma. Animals One hundred and fifty‐eight client‐owned dogs with naïve or relapsed multicentric lymphoma were prospectively enrolled from January to October 2019. Methods Dogs were randomized to receive RAB or placebo at a 3 : 1 ratio. Treatment was given every 21 days for up to 5 treatments. Study endpoints included progression‐free survival (PFS), overall response rate (ORR) at a given visit, best overall response rate (BORR), and percent progression free 1 month after treatment completion. Safety data were also collected. Results The median PFS was significantly longer in the RAB group compared to placebo (82 vs 21 days; P < .0001, HR 6.265 [95% CI 3.947‐9.945]). The BORR for RAB‐treated dogs was 73.2% (50.9% complete response [CR], 22.3% partial response [PR]) and 5.6% (0% CR, 5.6% PR) for placebo‐treated dogs ( P < .0001). One month after the last treatment, 37 RAB‐treated dogs (33%) were progression free compared with no placebo‐treated dogs ( P < .0001). The most common adverse events observed in the RAB group were diarrhea (87.5%), decreased appetite (68.3%), and vomiting (68.3%) and were generally low grade and reversible. Serious adverse events were reported in 24 RAB‐treated (20%) and 5 placebo‐treated dogs (13%). Conclusions and Clinical Importance Rabacfosadine demonstrated statistically significant antitumor efficacy in dogs with lymphoma when administered every 21 days for up to 5 treatments as compared to placebo.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Multicenter, randomized, double‐blinded, placebo‐controlled study of rabacfosadine in dogs with lymphoma

Weishaar

Wright

Rosenberg

et al. 2021

Veterinary Internal Medicne

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“…Canine lymphoma is a multicentric disease treated with systemic chemotherapy and is a useful model to study the impact of chemotherapy on cellular senescence. Doxorubicin, an anthracycline chemotherapeutic, was chosen as it is commonly used in the treatment of canine lymphoma (Al‐Nadaf et al., 2018 ; Mutsaers et al., 2002 ; Vail et al., 2020 ). Doxorubicin causes cytotoxicity via multiple mechanisms including DNA intercalation, topoisomerase I and II inhibition, generation of reactive oxygen species and is a known inducer of cellular senescence (Demaria et al., 2017 ; J. Ewald et al., 2008 ; J.…”

Section: Discussionmentioning

confidence: 99%

“…Lymphoma represents 7%–24% of canine neoplasias. Although multi‐agent chemotherapy induces clinical remission in greater than 80% of patients, more than half of dogs succumb to disease within a year due to chemotherapy resistance (Vail et al., 2020 ). Additionally, dogs experience chemotherapy toxicities similar to humans, with approximately 50% developing gastrointestinal or haematologic adverse events during multi‐agent CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

Serum IL‐6 and MCP‐1 concentrations in dogs with lymphoma before and after doxorubicin treatment as a potential marker of cellular senescence

Evans

Fenger

Ballash

et al. 2021

Veterinary Medicine & Sci

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Background: Chemotherapy can induce cellular senescence and a secretory phenotype characterized by an increased expression of inflammatory cytokines, such as IL-6 and MCP-1. Increased IL-6 and MCP-1 serum concentrations have been documented in dogs with lymphoma, but no studies have evaluated the effects of chemotherapy on cytokine concentrations.Objectives: To measure IL-6 and MCP-1 in 16 client-owned dogs with lymphoma, at baseline and before and after doxorubicin, as a potential marker for senescence and correlate cytokine concentrations with treatment response and toxicities.Methods: Serum IL-6 and MCP-1 concentrations at baseline, 0-h, 3-h, 6-h, 24-h and 1 week post doxorubicin were measured using a canine ELISA. We hypothesized that IL-6 and MCP-1 concentrations would increase following doxorubicin as a result of induction of cellular senescence.Results: IL-6 concentrations were unchanged from baseline to 0-h but significantly decreased 1 week post doxorubicin (p = 0.001) compared to 0-6 h (p = 0.045) and 24-h (p = 0.001) time points. MCP-1 concentrations significantly decreased from baseline to 0-h (p = 0.003). Compared to 0-6 h, MCP-1 concentrations transiently increased at 24h (p = 0.001) and decreased at 1 week (p = 0.014) post doxorubicin. Changes in IL-6 and MCP-1 concentrations did not correlate with leukocyte count, response to treatment or chemotherapy toxicities.Conclusions: Changes in IL-6 and MCP-1 concentrations did not support doxorubicininduced cellular senescence or correlate with leukocyte count, response to treatment or chemotherapy toxicity. However, our results suggest that remission status and doxorubicin treatment may influence cytokine concentrations and future studies are warranted to investigate the role of these cytokines as biomarkers.

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Preemptively planned en bloc resection of an extensive right adrenal pheochromocytoma involving the right hepatic division, caval thrombus and segmental caudal vena cava in a dog with Budd−Chiari‐like syndrome

Takeuchi

Ishigaki

Yoshida

et al. 2023

Veterinary Medicine & Sci

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Background: Surgical resection is the treatment of choice for canine adrenal pheochromocytomas (PHEOs). Information on en bloc resection of adrenal PHEO with tumour thrombus, right hepatic division and segmental caudal vena cava (CVC) running through the adrenal tumour and right hepatic division is limited.Objective: To describe the preemptively planned en bloc resection of an extensive right adrenal PHEO involving the right hepatic division, the caval thrombus and the segmental CVC in a dog with Budd−Chiari-like syndrome (BCLS). Methods:A 13-year-old castrated male miniature dachshund was referred for surgical treatment due to anorexia, lethargy and severe abdominal distension caused by abundant ascites. Preoperative computed tomography (CT) revealed a large mass in the right adrenal gland with a large caval thrombus obstructing the CVC and hepatic veins, which caused BCLS. Additionally, collateral vessels were formed between the CVC and azygos veins. No findings suggested obvious metastases. Based on CT findings, an en bloc resection of the adrenal tumour with caval thrombus, right hepatic division and segmental CVC was planned. Results:The preoperatively planned resection was feasible; the tumour was completely resected grossly. The operation time and total Pringle manoeuvre time were 162 min and 16 min 56 s, respectively. There was no postoperative hindlimb oedema, renal dysfunction, ascites or abdominal distention. The patient's clinical signs, including appetite, fully improved. Hospitalization lasted 16 days. However, the patient died on the 130th postoperative day due to suspected metastases and cachexia. Conclusions:Even in case of an extensive infiltration of adrenal PHEO causing BCLS, an en bloc resection might be successfully achieved based on the preoperative CT findings speculating the collateral vessels formed for caudal venous return.

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The Etiology of Cancer

Cited by 69 publications

References 307 publications

Multicenter, randomized, double‐blinded, placebo‐controlled study of rabacfosadine in dogs with lymphoma

Multicenter, randomized, double‐blinded, placebo‐controlled study of rabacfosadine in dogs with lymphoma

Serum IL‐6 and MCP‐1 concentrations in dogs with lymphoma before and after doxorubicin treatment as a potential marker of cellular senescence

Preemptively planned en bloc resection of an extensive right adrenal pheochromocytoma involving the right hepatic division, caval thrombus and segmental caudal vena cava in a dog with Budd−Chiari‐like syndrome

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