In vitro chemosensitivity of feline injection site‐associated sarcoma cell lines to carboplatin

Maxwell, Elizabeth; Phillips, Heidi S.; Schaeffer, David J.; Fan, Timothy M.

doi:10.1111/vsu.12709

Cited by 9 publications

(24 citation statements)

References 48 publications

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“…In the present study, calculated carboplatin tissue concentrations were below the reported mean half maximal inhibitory concentration (IC 50 ) for FISS cells at 72 hours . To achieve specific localized cytotoxicity for FISS, it might be feasible to consider increasing the density of bead placement in tumor‐bearing cats.…”

Section: Discussionmentioning

confidence: 68%

“…Most of the Pt release occurred within the first week in this study, with mean peak Pt concentrations diffusing to a radial distance of 2 cm by day 7 and to all distances at low concentrations for up to 21 days. Although Pt was detectable in tissues at day 21, concentrations at that time were below cytotoxic concentrations reported in vitro for canine and feline cancer cells . Spacing closer than 2 cm may be required to maintain cytotoxic concentrations of Pt in the tumor bed.…”

Section: Discussionmentioning

confidence: 75%

“…Carboplatin‐impregnated calcium sulfate hemihydrate (C‐I CSH) beads (Matrix III; Royer Animal Health, Frederick, Maryland) are intended for implantation at sites of gross tumor or of marginal tumor extirpation and release a platinum (Pt)‐containing chemotherapeutic agent at concentrations in vitro capable of inhibiting tumor cell growth . If cytotoxic concentrations are achievable in in vivo situations, C‐I CSH beads might have clinical utility as a local chemotherapeutic delivery device.…”

Section: Introductionmentioning

confidence: 99%

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Pharmacokinetics of platinum and safety evaluation of carboplatin‐impregnated calcium sulfate hemihydrate beads after implantation in healthy cats

et al. 2020

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Objective: To evaluate the pharmacokinetics (PK) of platinum (Pt) and safety of carboplatin-impregnated calcium sulfate hemihydrate (C-I CSH) beads after implantation in healthy cats. Study design:In vivo experimental study. Animals: Six healthy adult cats.Methods: Three C-I CSH beads were implanted in muscle pockets over the right and left hemithoraces of each cat (~3.9 mg/kg of Pt; 60.4 mg/m 2 of calculated carboplatin). Hematology and blood chemistry were tested at baseline and 3, 7, 14, and 21 days postimplantation. Serum was analyzed for Pt at specific times from 1 hour to 21 days. Tissue was obtained for histopathology and analysis of Pt at 3, 7, 14, and 21 days at standardized distances from implantation sites.Results: Platinum was detected in tissues at all times and distances (range, 0.1-4.19 μg/g). Serum Pt increased up to 2.6 hours (3.25 μg/mL) then decreased sharply. Samples containing muscle had higher Pt compared with samples without muscle (P = .004). Mild hypercalcemia was noted in four cats, and mild inflammatory reaction was noted on histopathology of all samples.Results of this study were presented in part at

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Section: Discussionmentioning

confidence: 68%

Section: Discussionmentioning

confidence: 75%

Section: Introductionmentioning

confidence: 99%

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Pharmacokinetics of platinum and safety evaluation of carboplatin‐impregnated calcium sulfate hemihydrate beads after implantation in healthy cats

et al. 2020

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“…In vitro chemosensitivities of various malignancies including canine mammary gland cancer, feline injection siteassociated sarcoma (FISAS), and canine osteosarcoma have been reported in only a handful of veterinary publications. [35][36][37] The concentration of carboplatin required to inhibit 50% of cellular activity (IC 50 ), which is viewed as an indicator for expected efficacy of chemotherapeutic agents, was studied. 38 The findings in these studies were consistent; the ability of carboplatin to inhibit cellular activity was both time and concentration dependent with mean IC 50 values ranging from 87.5 μM at 24 hours to 30.5 μM at 72 hours for the mammary gland tumors and 68.3 μM at 24 hours to 34.1 μM at 72 hours for the FISAS and considerably lower values for the osteosarcoma cells.…”

Section: Discussionmentioning

confidence: 99%

Repeatability of in vitro carboplatin elution from carboplatin‐impregnated calcium sulfate hemihydrate beads made in a clinic setting

Worth¹,

Risselada²,

Cooper³

et al. 2020

Veterinary Surgery

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Objective: To evaluate the intra-lot and inter-lot consistency and total carboplatin elution over 25 days from carboplatin-impregnated calcium sulfate hemihydrate (C-I CSH) beads manufactured in a clinic setting. Study design: In vitro elution study. Methods: Two volumes of carboplatin were mixed with CSH to yield 4 mg and 8 mg C-I CSH doses. Two lots of beads were made for each concentration and split into five doses (n = 10 per concentration). Beads hardened in molds and were placed in a covered six-well plate, submerged in phosphate-buffered saline, and incubated with samples collected at 12 time points (0, 6, 12, and 24 hours and 2, 3, 5, 7, 10, 14, 18, and 25 days). The amount of carboplatin in each sample was evaluated by high-performance liquid chromatography/mass spectrometry. Correction for carboplatin degradation and dilution was applied, and eluted carboplatin was calculated. Intra-lot and inter-lot coefficient of variation (CV) was calculated for each concentration. Results: The intra-lot CV ranged between 7.9% and 23.1%, and the inter-lot CV ranged from 3.5% to 10.3%, with improvement noted in each successive lot of beads. Mean peak eluted carboplatin was 2.45 ± 0.43 mg (61%) and 3.68 ± 0.41 mg (45.9%) for the 4-mg and 8-mg C-I CSH beads, respectively, with both occurring at the 12-hour timepoint. Conclusion: Progressive improvement in variability with successive lots of beads indicated a learning curve with bead manufacturing with a low variation both within and between lots of C-I CSH beads. Clinical significance: On-site mixing of carboplatin with commercial CSH bead powder leads to a low variation of carboplatin per bead dose.

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“…The effective in vivo tissue concentration of carboplatin carrying antitumor effects is unknown. In vitro studies have evaluated the half maximal inhibitory concentration (IC 50 ) of carboplatin for different neoplastic cell lines, which corresponds to the dose required to achieve 50% inhibition of neoplastic cell replication in vitro [13][14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of bioabsorbable calcium sulfate hemihydrate beads for local delivery of carboplatin

Traverson¹,

Stewart²,

Papich³

2020

PLoS ONE

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The objectives of this study were to evaluate a novel kit of resorbable calcium sulfate beads marketed specifically for use in veterinary medicine and generally used for local delivery of antimicrobials as carboplatin-delivery system. The study characterized the elution of carboplatin in vitro, and investigated whether the initial dose and formulation of carboplatin, or the bead size significantly influences carboplatin elution in vitro. Calcium sulfate hemihydrate beads of 3- and 5-mm diameter were prepared. Five doses and two formulations of carboplatin (20, 50, 100, and 500 mg carboplatin per kit in powder formulation; 20 mg in liquid formulation) were tested in triplicates for each diameter beads. Beads were placed in 37°C phosphate buffered saline for 72 hours. Carboplatin concentrations in the eluent were measured by high-performance liquid chromatography at 11 time points with a modified United States Pharmacopeia assay. Concentrations of carboplatin in the eluent proportionally increased with the initial dose and peaked between 13 and 52 hours, ranging from 42.1% to 79.3% of the incorporated load. Higher peak concentrations, percentages released, and elution rates were observed with the liquid formulation and with higher carboplatin doses. There was no significant difference in maximum carboplatin concentrations between 3- and 5-mm diameter beads, but 5-mm diameter beads had slower elution rates. The novel kit can be used for preparation of carboplatin-impregnated resorbable calcium sulfate beads at variable doses, sizes and formulations. Further study is warranted to define the in vivo requirements and effective carboplatin dose, spatial diffusion and desired duration of elution.

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In vitro chemosensitivity of feline injection site‐associated sarcoma cell lines to carboplatin

Cited by 9 publications

References 48 publications

Pharmacokinetics of platinum and safety evaluation of carboplatin‐impregnated calcium sulfate hemihydrate beads after implantation in healthy cats

Pharmacokinetics of platinum and safety evaluation of carboplatin‐impregnated calcium sulfate hemihydrate beads after implantation in healthy cats

Repeatability of in vitro carboplatin elution from carboplatin‐impregnated calcium sulfate hemihydrate beads made in a clinic setting

Evaluation of bioabsorbable calcium sulfate hemihydrate beads for local delivery of carboplatin

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