Analysis of platinum content in biodegradable carboplatin-impregnated beads and retrospective assessment of tolerability for intralesional use of the beads in dogs following excision of subcutaneous sarcomas: 29 cases (2011–2014)

Abstract

OBJECTIVE To evaluate platinum content in biodegradable carboplatin-impregnated beads and retrospectively assess tolerability and outcome data for dogs treated by intralesional placement of such beads following surgical excision of subcutaneous sarcomas. DESIGN Evaluation study and retrospective case series. SAMPLE 9 carboplatin-impregnated beads and 29 client-owned dogs. PROCEDURES Platinum content in 9 carboplatin-impregnated beads from 3 lots was measured by spectrophotometry, and calculated carboplatin content was compared with the labeled content. Medical records were searched to identify dogs with subcutaneous sarcomas for which treatment included placement of carboplatin-impregnated beads between 2011 and 2014. Signalment, tumor characteristics, surgical and histologic data, adverse events, and local recurrences were recorded. Associations between variables of interest and adverse events or local disease-free interval were analyzed. RESULTS In vitro analysis identified a mean ± SD platinum content of 5.38 ± 0.97 mg/bead. Calculated carboplatin content (10.24 ± 1.84 mg/bead) was significantly greater than the labeled amount (4.6 mg/bead). Bead weight and total platinum content differed significantly among lots, but platinum content per bead weight did not. Mild-to-moderate local adverse events were reported for 11 of 29 tumors; all resolved without additional surgery. No dogs had signs of systemic toxicosis. Overall local disease-free rates 1, 2, and 3 years after surgery were 70%, 70%, and 58%, respectively, as determined by Kaplan-Meier analysis. CONCLUSIONS AND CLINICAL RELEVANCE Carboplatin-impregnated beads were well tolerated; however, results of in vitro tests indicated that caution is needed because of manufacturing inconsistencies.

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

“…On the basis of the labeled content of 2.4 mg Pt per bead, each cat should have received a total local dose of 14.4 mg of Pt (3.9 mg/kg of Pt; 60.4 mg/m 2 of calculated carboplatin). Platinum content in C‐I CSH beads was found to be variable in a recent study . However, Pt release was consistent among beads from different manufacturer lot numbers as well as the sampling methods evaluated in two in vitro elution studies .…”

“…Whole blood samples were obtained for Pt analysis at 1, 2, 3, 6, 12, and 24 hours and at 2, 3, 7, 14, and 21 days PI. Total Pt concentrations are routinely used as consistent estimates of Pt‐based drug in serum and tissues . The samples were centrifuged, and serum was stored frozen at approximately −80°C.…”

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

“…However, these substrates are not commercially available, have shown unacceptable local toxicity such as wound dehiscence and infection, or have resulted in equivocal clinical improvement . In contrast, CSH beads are biocompatible and biodegradable, with minimal local reactivity and rare to no systemic toxicity . Based on previous studies and results of the present study, implantation of CI‐CSH beads may improve survival by delivering high concentrations of carboplatin directly to the site of greatest need, the extirpated tumor bed …”

“…Cisplatin and carboplatin delivery systems based on substrates such as open‐cell polylactic acid (OPLA‐Pt), hyaluronic acid, and others have been found effective against canine appendicular osteosarcoma, nasal tumors, and soft tissue sarcomas . However, these substrates are not commercially available, have shown unacceptable local toxicity such as wound dehiscence and infection, or have resulted in equivocal clinical improvement .…”

“…Local administration of cisplatin and carboplatin has been studied as a strategy to decrease systemic toxicity . Carboplatin‐impregnated CSH (CI‐CSH) beads are a commercially available delivery system (Wedgewood Pharmacy, Swedesboro, New Jersey) for sustained release of carboplatin following implantation at sites of gross tumor or of marginal tumor extirpation.…”