Decreased Recurrence in Sarcoma Patient-Derived Xenografts Using Paclitaxel-Eluting Polymer Films
David A. Mahvi1; Catalina Bordeianu2; Ngoc-Quynh Chu3; Jeremy Miller2; Robert Sabatelle2; Rong Liu3; Mark W. Grinstaff2; Yolonda L. Colson3; Chandrajit P. Raut1
1Brigham and Women's Hospital, Boston, MA; 2Boston University, Boston, MA; 3Massachusetts General Hospital, Boston, MA
Background: Despite macroscopically complete resection, locoregional recurrence of retroperitoneal sarcoma remains high and is the primary driver of patient mortality. The efficacy of a novel paclitaxel-loaded polymer film was assessed in two separate patient-derived xenograft murine models.
Methods: 1x1 cm poly(glycerol monostearate-co-caprolactone) polymer films were either loaded with no paclitaxel (unloaded), with covalently-bound paclitaxel to the polymer backbone (Single-Pax), or with both covalently-bound and free paclitaxel (Double-Pax). LP6 liposarcoma and LMS20 leiomyosarcoma were grown subcutaneously in nude mice. Following resection, mice were intraoperatively randomized to: (1) Double-Pax film, (2) Single-Pax film+300 µg intraperitoneal Pax, (3) Unloaded film, (4) no other therapy (n=8 per group).
Results: Following LP6 R1 resection, only one mouse receiving a double-Pax film recurred. 100% of mice in all other groups in the LP6 cohort recurred within 30 days (p=0.0002) and died within 40 days (p<0.0001). Following LMS20 subtotal R2 resection, 25% of Double-Pax film and 50% of Single-Pax mice died of recurrent local tumor. In contrast, 87.5% of “no other therapy” and 100% of other groups recurred locally and died (p=0.0009). No mice experienced a significant postoperative body weight drop or film-related morbidity.
Conclusion: 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 patient-derived xenograft models of the two most common histologies.
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