Decreased Recurrence in Sarcoma Using Double-Loaded Paclitaxel-Eluting Polymer Films
*David A Mahvi1, *Catalina Bordeianu2, *Ngoc-Quynh Chu1, *Jeremy Miller2, *Mark W Grinstaff2, *Yolonda L Colson3, Chandrajit P Raut1
1Brigham and Women's, Boston, MA;2Boston University, Boston, MA;3Massachusetts General Hospital, Boston, MA
Objective: Despite macroscopically complete resection, locoregional recurrence of sarcoma remains high. The efficacy of a novel double-loaded paclitaxel-eluting polymer film was assessed in two separate murine models of recurrent sarcoma.
Design: 1x1 cm poly(glycerol monostearate-co-caprolactone) polymer films were electrospun onto a polyglycolic acid buttress. Films were either loaded with no paclitaxel (unloaded), with paclitaxel covalently-bound to the polymer backbone (single-Pax), or with both covalently-bound and free paclitaxel (double-Pax). Cell-line CS-1 chondrosarcoma and patient-derived xenograft (PDX) LP-6 liposarcoma were grown subcutaneously in nude mice. Following R1 resection, mice were intraoperatively randomized to: (1) Double-Pax film, (2) Single-Pax film, (3) Unloaded film, (4) intraperitoneal (IP) paclitaxel, or (5) no other therapy. Local recurrence and overall survival were assessed for 90 days.
Interventions: see above
Main Outcome Measures: Recurrence-free Survival
Results: There were no recurrences within 90 days for the mice receiving double-Pax films for CS-1 and one recurrence for LP-6. The median time to locoregional recurrence in the CS-1 model was not reached for double-Pax films, 13 days for no treatment and unloaded film, 13.5 days for IP paclitaxel, and 23 days for single-Pax films (p<0.0001). The median time to locoregional recurrence in the LP-6 model was not reached for double-Pax film, 10 days for no treatment, 14 days for unloaded film, and 13 days for single-Pax film+IP paclitaxel (p=0.0002).
Conclusions: A novel paclitaxel-eluting polymer film double-loaded with both free and covalently-bound drug shows superior efficacy in preventing sarcoma recurrence in two separate murine models, including PDX liposarcoma.
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