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

We conducted a prospective phase I study to evaluate safety of an orally administered Salmonella encoding IL‐2 (SalpIL2) in combination with amputation and adjuvant doxorubicin for canine appendicular osteosarcoma. Efficacy was assessed as a secondary measure. The first dose of SalpIL2 was administered to 19 dogs on Day 0; amputation was done after 10 days with chemotherapy following 2 weeks later. SalpIL2 was administered concurrent with chemotherapy, for a total of five doses of doxorubicin and six doses of SalpIL2. There were six reportable events prior to chemotherapy, but none appeared due to SalpIL2. Dogs receiving SalpIL2 had significantly longer disease‐free interval (DFI) than a comparison group of dogs treated with doxorubicin alone. Dogs treated using lower doses of SalpIL2 also had longer DFI than dogs treated using the highest SalpIL2 dose. The data indicate that SalpIL2 is safe and well tolerated, which supports additional testing to establish the potential for SalpIL2 as a novel form of adjuvant therapy for dogs with osteosarcoma.

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“…; Lane et al . ). In dogs, IL‐2 has been shown to have clinical efficacy against soft tissue sarcomas and osteosarcoma (Mengesha et al .…”

Section: Introductionmentioning

confidence: 97%

A phase I clinical study to evaluate safety of orally administered, genetically engineeredSalmonella entericaserovarTyphimuriumfor canine osteosarcoma

Fritz

Henson

Greengard

et al. 2016

Veterinary Medicine & Sci

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“…doxorubicin and platinum compounds (reviewed in [24]). Current therapeutic development for canine osteosarcoma involves the modification of current protocols and Standard of Care (SOC) agents with limited success [43], rather than the integration of new therapeutic agents as single or combinational therapy. Personalized medicine strategies provide an opportunity to expand a patient’s “therapeutic opportunities” by examining the molecular/biological factors that are fundamental to that individual’s disease etiology and progression.…”

Section: Discussionmentioning

confidence: 99%

A multi-site feasibility study for personalized medicine in canines with Osteosarcoma

et al. 2013

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BackgroundA successful therapeutic strategy, specifically tailored to the molecular constitution of an individual and their disease, is an ambitious objective of modern medicine. In this report, we highlight a feasibility study in canine osteosarcoma focused on refining the infrastructure and processes required for prospective clinical trials using a series of gene expression-based Personalized Medicine (PMed) algorithms to predict suitable therapies within 5 days of sample receipt.MethodsTumor tissue samples were collected immediately following limb amputation and shipped overnight from veterinary practices. Upon receipt (day 1), RNA was extracted from snap-frozen tissue, with an adjacent H&E section for pathological diagnosis. Samples passing RNA and pathology QC were shipped to a CLIA-certified laboratory for genomic profiling. After mapping of canine probe sets to human genes and normalization against a (normal) reference set, gene level Z-scores were submitted to the PMed algorithms. The resulting PMed report was immediately forwarded to the veterinarians. Upon receipt and review of the PMed report, feedback from the practicing veterinarians was captured.Results20 subjects were enrolled over a 5 month period. Tissue from 13 subjects passed both histological and RNA QC and were submitted for genomic analysis and subsequent PMed analysis and report generation. 11 of the 13 samples for which PMed reports were produced were communicated to the veterinarian within the target 5 business days. Of the 7 samples that failed QC, 4 were due to poor RNA quality, whereas 2 were failed following pathological review. Comments from the practicing veterinarians were generally positive and constructive, highlighting a number of areas for improvement, including enhanced education regarding PMed report interpretation, drug availability, affordable pricing and suitable canine dosing.ConclusionsThis feasibility trial demonstrated that with the appropriate infrastructure and processes it is possible to perform an in-depth molecular analysis of a patient’s tumor in support of real time therapeutic decision making within 5 days of sample receipt. A number of areas for improvement have been identified that should reduce the level of sample attrition and support clinical decision making.

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“…As Dr Jacobs states, the AUSVETPLAN manual for equine influenza has been updated subsequent to the 2007/2008 outbreak. 2 The critical issue with regard to vaccination will be access to adequate quantities of an appropriate vaccine. At this stage, the respective horse-owning organisations have not established improved access to an emergency supply of vaccines should the need arise.…”

Section: Re: Equine Influenza Supplementmentioning

confidence: 99%

“…The second paper is a retrospective study of the efficacy and toxicity of a post-amputation chemotherapy protocol for appendicular osteosarcoma that comprises two initial doses of doxorubicin, followed by four doses of carboplatin. 2 Although numerous randomised trials have been performed in human oncology, canine treatment is often based on extrapolation from single case studies or case series. This retrospective study included 33 dogs and showed little improvement in median overall survival, but marked increase in toxicity.…”

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confidence: 99%

In this issue – March 2012

Jackson¹

2012

Aust Veterinary J

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

Cited by 21 publications

References 27 publications

A phase I clinical study to evaluate safety of orally administered, genetically engineeredSalmonella entericaserovarTyphimuriumfor canine osteosarcoma

A phase I clinical study to evaluate safety of orally administered, genetically engineeredSalmonella entericaserovarTyphimuriumfor canine osteosarcoma

A multi-site feasibility study for personalized medicine in canines with Osteosarcoma

In this issue – March 2012

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