{
    "abstract": "Imiquimod is a toll-like receptor agonist with proven antitumor activity as a topical treatment for skin cancer. TMX-101 (Vesimune) is a novel liquid formulation of imiquimod optimized for intravesical delivery. The agent demonstrated safety as an intravesical treatment for non-muscle-invasive bladder cancer in a phase 1 clinical trial. We report the results of a phase 2 prospective multicenter clinical trial assessing the safety and activity of TMX-101.\nPatients with non-muscle-invasive bladder cancer containing carcinoma in situ were eligible for inclusion. Enrolled patients received 6 weekly intravesical administrations of 200mg/50ml TMX-101 0.4%. End points included rate of adverse events, changes in urinary cytokine levels following treatment, and clinical response at 6 weeks following final instillation, defined as negative posttreatment bladder biopsy and urine cytology results.\nA total of 12 patients were enrolled, with 10 available for efficacy analysis. Half of the patients (6/12) had received\u22652 prior induction courses of bacillus Calmette-Guerin. All patients received all 6 doses of TMX-101 per protocol. Overall, 75% of patients experienced treatment-related adverse events, only 1 of which was>grade 2 (urinary tract infection). Furthermore, 2 patients demonstrated a negative cytology and biopsy result at 6 weeks following treatment. Significant increases in urinary cytokines, including IL-6 and IL-18, were seen following treatment.\nIn this phase 2 pilot study in patients with carcinoma in situ bladder cancer, intravesical TMX-101 was safe and well tolerated with common, mild genitourinary adverse effects. Clinical activity was suggested by the increase in posttreatment urinary cytokines. Complete responders were seen. Further investigation of the agent is warranted.",
    "authors": [
        {
            "affiliation": "Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, CA. Electronic address: NDonin@mednet.ucla.edu.",
            "firstname": "Nicholas M",
            "initials": "NM",
            "lastname": "Donin"
        },
        {
            "affiliation": "Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, CA.",
            "firstname": "Karim",
            "initials": "K",
            "lastname": "Chamie"
        },
        {
            "affiliation": "Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, CA.",
            "firstname": "Andrew T",
            "initials": "AT",
            "lastname": "Lenis"
        },
        {
            "affiliation": "Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, CA.",
            "firstname": "Allan J",
            "initials": "AJ",
            "lastname": "Pantuck"
        },
        {
            "affiliation": "Division of Urology, Hahnemann University Hospital, Philadephia, PA.",
            "firstname": "Madhu",
            "initials": "M",
            "lastname": "Reddy"
        },
        {
            "affiliation": "Division of Urology, Hahnemann University Hospital, Philadephia, PA.",
            "firstname": "Dana",
            "initials": "D",
            "lastname": "Kivlin"
        },
        {
            "affiliation": "Telormedix SA, Bioggio, Switzerland.",
            "firstname": "Johanna",
            "initials": "J",
            "lastname": "Holldack"
        },
        {
            "affiliation": "Telormedix SA, Bioggio, Switzerland.",
            "firstname": "Rafaella",
            "initials": "R",
            "lastname": "Pozzi"
        },
        {
            "affiliation": "UroGen Pharma, Ra'anana, Israel.",
            "firstname": "Gil",
            "initials": "G",
            "lastname": "Hakim"
        },
        {
            "affiliation": "The Urology Center of Colorado, Denver, CO.",
            "firstname": "Lawrence I",
            "initials": "LI",
            "lastname": "Karsh"
        },
        {
            "affiliation": "BCG Oncology, Phoenix, AZ.",
            "firstname": "Donald L",
            "initials": "DL",
            "lastname": "Lamm"
        },
        {
            "affiliation": "Division of Urology, Hahnemann University Hospital, Philadephia, PA.",
            "firstname": "Laurence H",
            "initials": "LH",
            "lastname": "Belkoff"
        },
        {
            "affiliation": "Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, CA.",
            "firstname": "Arie S",
            "initials": "AS",
            "lastname": "Belldegrun"
        },
        {
            "affiliation": "Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, CA.",
            "firstname": "Stuart",
            "initials": "S",
            "lastname": "Holden"
        },
        {
            "affiliation": "Carolina Urologic Research Center, Myrtle Beach, SC.",
            "firstname": "Neal",
            "initials": "N",
            "lastname": "Shore"
        }
    ],
    "conclusions": "In this phase 2 pilot study in patients with carcinoma in situ bladder cancer, intravesical TMX-101 was safe and well tolerated with common, mild genitourinary adverse effects. Clinical activity was suggested by the increase in posttreatment urinary cytokines. Complete responders were seen. Further investigation of the agent is warranted.",
    "copyrights": "Copyright \u00a9 2017 Elsevier Inc. All rights reserved.",
    "doi": "10.1016/j.urolonc.2016.09.006",
    "journal": "Urologic oncology",
    "keywords": [
        "Administrations, intravesical drug",
        "Carcinoma in situ",
        "Imiquimod",
        "Immunotherapy",
        "Urinary bladder neoplasms"
    ],
    "methods": null,
    "publication_date": "2017-03-28",
    "pubmed_id": "28341495",
    "results": "A total of 12 patients were enrolled, with 10 available for efficacy analysis. Half of the patients (6/12) had received\u22652 prior induction courses of bacillus Calmette-Guerin. All patients received all 6 doses of TMX-101 per protocol. Overall, 75% of patients experienced treatment-related adverse events, only 1 of which was>grade 2 (urinary tract infection). Furthermore, 2 patients demonstrated a negative cytology and biopsy result at 6 weeks following treatment. Significant increases in urinary cytokines, including IL-6 and IL-18, were seen following treatment.",
    "title": "A phase 2 study of TMX-101, intravesical imiquimod, for the treatment of carcinoma in situ bladder cancer.",
    "xml": "<Element 'PubmedArticle' at 0x788506a0e6b0>"
}