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

ABSTRACT: 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&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 < 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 < 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.

SUBMITTER: Maulhardt HA

PROVIDER: S-EPMC6520999 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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

Maulhardt Holly A HA Hylle Lauren L Frost Michael V MV Tornio Ashley A Dafoe Sara S Drummond Leanne L Quinn David I DI Kamat Ashish M AM diZerega Gere S GS

Cancers 20190424 4

Intratumoral (IT) administration of submicron particle docetaxel (NanoDoce<sup>®</sup>, 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<sup>®</sup>, 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 ...[more]

PMID: 31022918

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Project description:PurposeTo investigate the health-related quality of life of uro-oncologic patients whose surgery was postponed without being rescheduled during the coronavirus disease 2019 (COVID-19) pandemic.Patients and methodsFrom the March 1 to April 26, 2020, major urologic surgeries were drastically reduced at our tertiary-care referral hospital. In order to evaluate health-related quality-of-life outcomes, the SF-36 questionnaire was sent to all patients scheduled for major surgery at our department 3 weeks after the cancellation of the planned surgical procedures because of the COVID-19 emergency.ResultsAll patients included in the analysis had been awaiting surgery for a median (interquartile range) time of 52.85 (35-72) days. The SF-36 questionnaire measured 8 domains: physical functioning (PF), role limitations due to physical health (PH), role limitations due to emotional problems (RE), energy/fatigue (EF), emotional well-being (EWB), social functioning (SF), bodily pain (BP), general health perceptions (GHP). When considering physical characteristics as measured by the SF-36 questionnaire, PF was 91.5 (50-100) and PH was 82.75 (50-100) with a BP of 79.56 (45-90). For emotional and social aspects, RE was 36.83 (0-100) with a SF of 37.98 (12.5-90). Most patients reported loss of energy (EF 35.28 [15-55]) and increased anxiety (EWB 47.18 [interquartile range, 20-75]). All patients perceived a reduction of their health conditions, with GHP of 49.47 (15-85). Generally, 86% of patients (n = 43) noted an almost intact physical function but a significant emotional alteration characterized by a prevalence of anxiety and loss of energy.ConclusionThe lockdown due to the novel coronavirus that has affected most operating rooms in Italy could be responsible for the increased anxiety and decrement in health status of oncologic patients. Without any effective solution, we should expect a new medical catastrophe-one caused by the increased risk of tumor progression and mortality in uro-oncologic patients.

Dataset Information

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

Publications

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

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