Survival analysis of dogs with advanced primary lung carcinoma treated by metronomic cyclophosphamide, piroxicam and thalidomide

Polton, Gerry; Finotello, Riccardo; Sabattini, Silvia; Rossi, Federica; Laganga, Paola; Vasconi, Maria Elisabetta; Barbanera, Andrea; Stiborova, Katerina; Bley, Carla Rohrer; Marconato, Laura

doi:10.1111/vco.12393

Cited by 28 publications

(45 citation statements)

References 37 publications

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“…In canine prostatic carcinoma, both piroxicam and carprofen (a preferential COX‐2 inhibitor; this class of drugs affects both COX‐1 and COX‐2 but is more selective towards COX‐2) significantly increased survival time as single agents when compared to untreated dogs in both early stage and metastatic disease . As part of dual modality treatment and metronomic chemotherapy, piroxicam significantly increased survival time and incidences of complete or partial remission compared to the same treatments without piroxicam in a range of cancer types including invasive urothelial carcinoma and primary lung carcinoma . A recent review on canine mammary carcinoma concludes that including NSAIDs in treatment significantly improves survival, especially in inflammatory mammary carcinomas when NSAIDs are used alone as palliative treatment or in combination with chemotherapy .…”

Section: Discussionmentioning

confidence: 99%

“…In many cases curative treatment is not an option and palliative care is opted for. In the studies mentioned above, several factors used to assess quality of life (including appetite, activity levels and pain) were all noted to be improved in patients treated with NSAIDs (reported through owner questionnaires), even in cases where NSAIDs showed no improvement in survival time compared to other treatment options . In one study, most owners requested that their dogs remain on piroxicam treatment even if tumour remission did not occur, due to their subjective improvement in quality of life .…”

Section: Discussionmentioning

confidence: 99%

“…In the studies mentioned above, several factors used to assess quality of life (including appetite, activity levels and pain) were all noted to be improved in patients treated with NSAIDs (reported through owner questionnaires), even in cases where NSAIDs showed no improvement in survival time compared to other treatment options. 95,99,101,102 In one study, most owners requested that their dogs remain on piroxicam treatment even if tumour remission did not occur, due to their subjective improvement in quality of life. 95 Given the importance of quality of life, this is clinically relevant finding and should be taken into consideration when decisions are made regarding treatment options in veterinary cancer care.…”

Section: Discussionmentioning

confidence: 99%

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The selective cyclooxygenase‐2 inhibitor mavacoxib (Trocoxil) exerts anti‐tumour effects in vitro independent of cyclooxygenase‐2 expression levels

Hurst

Pang

Argyle

2019

Vet Comparative Oncology

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The inducible inflammatory enzyme cyclooxygenase‐2 (COX‐2) and its product prostaglandin E2 (PGE2) are prominent tumour promoters, and expression of COX‐2 is elevated in a number of tumours of both humans and canines. Targeting COX‐2 in cancer is an attractive option because of readily available non‐steroidal anti‐inflammatory drugs (NSAIDs), and there is a clear epidemiological link between NSAID use and cancer risk. In this study, we aim to establish the anti‐tumourigenic effects of the selective, long‐acting COX‐2 inhibitor mavacoxib. We show here that mavacoxib is cytotoxic to a panel of human and canine osteosarcoma, mammary and bladder carcinoma cancer cell lines; that it can induce apoptosis and inhibit the migration of these cells. Interestingly, we establish that mavacoxib can exert these effects independently of elevated COX‐2 expression. This study highlights the potential novel use of mavacoxib as a cancer therapeutic, suggesting that mavacoxib may be an effective anti‐cancer agent independent of tumour COX‐2 expression.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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The selective cyclooxygenase‐2 inhibitor mavacoxib (Trocoxil) exerts anti‐tumour effects in vitro independent of cyclooxygenase‐2 expression levels

Hurst

Pang

Argyle

2019

Vet Comparative Oncology

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“…Recently, a multimodal protocol including toceranib, piroxicam and thalidomide with hypofractionated radiation therapy demonstrated clinical benefit in dogs with inflammatory mammary carcinoma (40); clinical benefit was also described in dogs with advanced primary lung carcinoma treated by metronomic cyclophosphamide, piroxicam and thalidomide (41). The addition of continuous thalidomide after surgical excision of splenic hemangiosarcoma in dogs was considered beneficial and suggested as a relevant therapy protocol for the disease (42).…”

Section: Discussionmentioning

confidence: 99%

Adjuvant Thalidomide and Metronomic Chemotherapy for the Treatment of Canine Malignant Mammary Gland Neoplasms

Campos

Lavalle

Monteiro³

et al. 2018

In Vivo

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Background/Aim: The aim of the present study was to evaluate a multimodal approach for the treatment of canine malignant mammary gland neoplasms, including surgery, chemotherapy, thalidomide, and metronomic chemotherapy (MC). Materials and Methods: Fifty-eight female dogs were submitted to four different treatments: surgery; surgery with chemotherapy; surgery with chemotherapy and thalidomide; and surgery with chemotherapy and metronomic chemotherapy and overall survival was evaluated. Results: No statistical difference was found in the proliferative index and microvessel density of primary neoplasms and distant metastases following thalidomide treatment. Diffuse intense inflammatory infiltrate was predominant in primary tumors and diffuse moderate inflammatory infiltrate in metastatic lesions. No statistically significant difference was observed in median survival time (MST) between treatment groups when including all clinical stages (p=0.3177). However, animals diagnosed with distant metastasis treated with surgery and chemotherapy associated with thalidomide or MC presented longer MST when compared to animals treated only with surgery or surgery and chemotherapy (p<0.0001). Conclusion: The proposed multimodal therapy protocols including antiangiogenic and immunomodulatory therapies demonstrated a clinical benefit for patients in advanced clinical stages. Many mammalian species present mammary gland neoplasms similar to breast cancer in women, and the high incidence of spontaneous disease in domestic dogs and cats characterize them as pertinent comparative models (1). Human and canine breast cancer incidence present similar proportional distribution by age and sex (2), and resemblance in type, molecular transformative abnormalities, and behavior. This enables comparative studies involving carcinogenesis and the efficacy of novel therapies in mammary neoplasms in pets (1). Mammary gland neoplasms are the most common neoplasms that affect female dogs (3). Although the optimal extent remains unclear (4), surgery remains the most effective treatment for the disease. Adjuvant therapies may be required for high-risk, undifferentiated and advanced neoplasms (5, 6). Single-agent treatments have been considered less efficacious than combination therapies (7), and in solid tumors, angiogenesis has clearly been associated with metastasis and disease progression (8), and the combination of antiangiogenic strategies with conventional chemotherapy protocols will likely benefit the treatment of malignant tumors (9). In the late 1950s, thalidomide was marketed worldwide as a sedative and a hypnotic, and as an anti-emetic drug in early pregnancy (10). Thalidomide was associated with congenital deformities and peripheral neuropathy, and the drug was 1659 This article is freely accessible online.

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“…Whereas, there is a clear relationship between cigarette smoking and the increased risk of developing lung cancer in people, no apparent environmental factors have been identified in dogs (10)(11)(12). The clinical signs in dogs are coughing in 50-93%, dyspnea, lethargy, anorexia, weight loss, hemoptysis, and lameness secondary to hypertrophic osteopathy or rarely metastatic lytic lesions (6,9,(13)(14)(15)(16)(17)(18). In up to 30% of cases, primary lung tumors are an incidental finding (6,9,13,16).…”

Section: Introductionmentioning

confidence: 99%

A Contemporary Retrospective Study of Survival in Dogs With Primary Lung Tumors: 40 Cases (2005–2017)

Rose

Worley

2020

Front. Vet. Sci.

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Patients were identified for inclusion if they had lung lobectomy and an intrathoracic lymph node biopsy performed. The median survival time (MST) for lymph node positive (LN+) and negative dogs (LN-) was calculated as well as the MST in dogs that did or did not receive adjuvant chemotherapy. Differences were compared between groups with significance set at p < 0.05. Results: The MST in LN+ dogs (n = 11) was 167 days which was not statistically different from LN-dogs (n = 29) at 456 days (p = 0.2407). No significant difference in the MST in LN+ dogs was identified between dogs that received adjuvant chemotherapy (n = 4; 110 days) and those that did not receive adjuvant chemotherapy (n = 6; 125 days) (p = 0.4409). There was no difference in survival time in LN-dogs receiving chemotherapy (n = 12; 335 days) as compared to those LN-dogs (n = 10) that did not receive adjuvant chemotherapy (258.5 days; p = 0.6475). Conclusions and Clinical Relevance: The survival of primary pulmonary neoplasia in dogs with intrathoracic nodal metastasis is longer than previously reported in this contemporary cohort. Chemotherapy did not appear to improve survival in LN+ or LNdogs. The combination of tumor size between 100 and 999 cm 3 and positive lymph node status significantly reduced survival.

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Survival analysis of dogs with advanced primary lung carcinoma treated by metronomic cyclophosphamide, piroxicam and thalidomide

Cited by 28 publications

References 37 publications

The selective cyclooxygenase‐2 inhibitor mavacoxib (Trocoxil) exerts anti‐tumour effects in vitro independent of cyclooxygenase‐2 expression levels

The selective cyclooxygenase‐2 inhibitor mavacoxib (Trocoxil) exerts anti‐tumour effects in vitro independent of cyclooxygenase‐2 expression levels

Adjuvant Thalidomide and Metronomic Chemotherapy for the Treatment of Canine Malignant Mammary Gland Neoplasms

A Contemporary Retrospective Study of Survival in Dogs With Primary Lung Tumors: 40 Cases (2005–2017)

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