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Intratumoral (IT) administration of submicron particle docetaxel (NanoDoce ® , NanOlogy LLC, Fort Worth, TX, USA) and its efficacy against genitourinary-oncologic xenografts in rats and mice, xenograft-site docetaxel concentrations and immune-cell infiltration were studied. IT-NanoDoce ® , IV-docetaxel and IT-vehicle were administered to clear cell renal carcinoma (786-O: rats), transitional cell bladder carcinoma (UM-UC-3: mice) and prostate carcinoma (PC-3: mice). Treatments were given every 7 days with 1, 2, or 3 doses administered. Animals were followed for tumor growth and clinical signs. At necropsy, 786-O and UM-UC-3 tumor-site tissues were evaluated by H&amp;E and IHC and analyzed by LC-MS/MS for docetaxel concentration. Two and 3 cycles of IT-NanoDoce ® significantly reduced UM-UC-3 tumor volume ( p &lt; 0.01) and eliminated most UM-UC-3 and 786-O tumors. In both models, NanoDoce ® treatment was associated with (peri)tumor-infiltrating immune cells. Lymphoid structures were observed in IT-NanoDoce ® -treated UM-UC-3 animals adjacent to tumor sites. IT-vehicle and IV-docetaxel exhibited limited immune-cell infiltration. In both studies, high levels of docetaxel were detected in NanoDoce ® -treated animals up to 50 days post-treatment. In the PC-3 study, IT-NanoDoce ® and IV-docetaxel resulted in similar tumor reduction. NanoDoce ® significantly reduced tumor volume compared to IT-vehicle in all xenografts ( p &lt; 0.0001). We hypothesize that local, persistent, therapeutic levels of docetaxel from IT-NanoDoce ® reduces tumor burden while increasing immune-cell infiltration. IT NanoDoce ® treatment of prostate, renal and bladder cancer may result in enhanced tumoricidal effects.

cancers

Local Injection of Submicron Particle Docetaxel is Associated with Tumor Eradication, Reduced Systemic Toxicity and an Immunologic Response in Uro-Oncologic Xenografts