1 Ocak 2022 Dergi makalesi Açık Erişim

Goldberg, Manijeh; Manzi, Aaron; Birdi, Amritpreet; Laporte, Brandon; Conway, Peter; Cantin, Stefanie; Mishra, Vasudha; Singh, Alka; Pearson, Alexander T.; Goldberg, Eric R.; Goldberger, Sam; Flaum, Benjamin; Hasina, Rifat; London, Nyall R.; Gallia, Gary L.; Bettegowda, Chetan; Young, Simon; Sandulache, Vlad; Melville, James; Shum, Jonathan; Shum, Jonathan

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    <subfield code="a">Despite therapeutic advancements, oral cavity squamous cell carcinoma (OCSCC) remains a difficult disease to treat. Systemic platinum-based chemotherapy often leads to dose-limiting toxicity (DLT), affecting quality of life. PRV111 is a nanotechnology-based system for local delivery of cisplatin loaded chitosan particles, that penetrate tumor tissue and lymphatic channels while avoiding systemic circulation and toxicity. Here we evaluate PRV111 using animal models of oral cancer, followed by a clinical trial in patients with OCSCC. In vivo, PRV111 results in elevated cisplatin retention in tumors and negligible systemic levels, compared to the intravenous, intraperitoneal or intratumoral delivery. Furthermore, PRV111 produces robust anti-tumor responses in subcutaneous and orthotopic cancer models and results in complete regression of carcinogen-induced premalignant lesions. In a phase 1/2, open-label, single-arm trial (NCT03502148), primary endpoints of efficacy (&amp;gt;= 30% tumor volume reduction) and safety (incidence of DLTs) of neoadjuvant PRV111 were reached, with 69% tumor reduction in similar to 7 days and over 87% response rate. Secondary endpoints (cisplatin biodistribution, loco-regional control, and technical success) were achieved. No DLTs or drug-related serious adverse events were reported. No locoregional recurrences were evident in 6 months. Integration of PRV111 with current standard of care may improve health outcomes and survival of patients with OCSCC.</subfield>
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    <subfield code="a">Goldberg, Manijeh</subfield>
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    <subfield code="a">10.1038/s41467-022-31859-3</subfield>
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    <subfield code="a">A nanoengineered topical transmucosal cisplatin delivery system induces anti-tumor response in animal models and patients with oral cancer</subfield>
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    <subfield code="a">Conway, Peter</subfield>
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    <subfield code="a">Cantin, Stefanie</subfield>
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    <subfield code="a">Mishra, Vasudha</subfield>
    <subfield code="u">Univ Chicago, Sect Hematol &amp; Oncol, Dept Med, Chicago, IL 60637 USA</subfield>
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    <subfield code="a">Singh, Alka</subfield>
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    <subfield code="a">Pearson, Alexander T.</subfield>
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    <subfield code="a">Hasina, Rifat</subfield>
    <subfield code="u">Univ Chicago, Sect Otolaryngol Head &amp; Neck Surg, Dept Surg, Chicago, IL 60637 USA</subfield>
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    <subfield code="a">Bettegowda, Chetan</subfield>
    <subfield code="u">Johns Hopkins Univ, Dept Neurosurg &amp; Oncol, Sch Med, Baltimore, MD USA</subfield>
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    <subfield code="a">Young, Simon</subfield>
    <subfield code="u">Univ Texas Hlth Sci Ctr, Dept Oral Maxillofacial Surg, Houston, TX USA</subfield>
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