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Results of a phase 1 dose escalation study of intravesical TMX-101 in patients with nonmuscle invasive bladder cancer.

PURPOSEImiquimod, a toll like receptor 7 (TLR-7) agonist, is effective as a topical treatment for skin malignancies. TMX-101 is a liquid formulation of imiquimod. In this study we establish a safety profile of TMX-101 in patients with nonmuscle invasive bladder cancer. MATERIALS AND METHODSWe conduc... Full description

Journal Title: The Journal of urology June 2013, Vol.189(6), pp.2077-2082
Main Author: Falke, Johannes
Other Authors: Lammers, Rianne J M , Arentsen, Harm C , Ravic, Miroslav , Pozzi, Raffaella , Cornel, Erik B , Vergunst, Henk , de Reijke, Theo M , Witjes, J Alfred
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1527-3792 ; DOI: 1527-3792 ; DOI: 10.1016/j.juro.2012.11.150
Link: http://search.proquest.com/docview/1350892117/?pq-origsite=primo
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title: Results of a phase 1 dose escalation study of intravesical TMX-101 in patients with nonmuscle invasive bladder cancer.
format: Article
creator:
  • Falke, Johannes
  • Lammers, Rianne J M
  • Arentsen, Harm C
  • Ravic, Miroslav
  • Pozzi, Raffaella
  • Cornel, Erik B
  • Vergunst, Henk
  • de Reijke, Theo M
  • Witjes, J Alfred
subjects:
  • Administration, Intravesical–Adverse Effects
  • Adult–Pharmacokinetics
  • Age Factors–Therapeutic Use
  • Aged–Adverse Effects
  • Aged, 80 and Over–Pharmacokinetics
  • Aminoquinolines–Therapeutic Use
  • Antineoplastic Agents–Drug Therapy
  • Carcinoma, Transitional Cell–Mortality
  • Cystoscopy–Pathology
  • Disease-Free Survival–Methods
  • Dose-Response Relationship, Drug–Methods
  • Drug Administration Schedule–Pathology
  • Female–Drug Therapy
  • Follow-Up Studies–Mortality
  • Humans–Pathology
  • Male–Pathology
  • Maximum Tolerated Dose–Pathology
  • Middle Aged–Pathology
  • Neoadjuvant Therapy–Pathology
  • Neoplasm Invasiveness–Pathology
  • Neoplasm Staging–Pathology
  • Netherlands–Pathology
  • Patient Safety–Pathology
  • Prospective Studies–Pathology
  • Risk Assessment–Pathology
  • Sex Factors–Pathology
  • Survival Rate–Pathology
  • Treatment Outcome–Pathology
  • Urinary Bladder Neoplasms–Pathology
  • Abridged
  • Aminoquinolines
  • Antineoplastic Agents
  • Imiquimod
ispartof: The Journal of urology, June 2013, Vol.189(6), pp.2077-2082
description: PURPOSEImiquimod, a toll like receptor 7 (TLR-7) agonist, is effective as a topical treatment for skin malignancies. TMX-101 is a liquid formulation of imiquimod. In this study we establish a safety profile of TMX-101 in patients with nonmuscle invasive bladder cancer. MATERIALS AND METHODSWe conducted a multicenter phase 1 dose escalation study in patients with nonmuscle invasive bladder cancer. Patients were included in 1 of 4 dose groups (0.05%, 0.1%, 0.2% or 0.4%) and treated with 6 weekly instillations of TMX-101, starting 2 weeks after transurethral resection of bladder tumor. Patients were evaluated weekly, and pharmacokinetic and pharmacodynamic parameters were measured. RESULTSA total of 16 patients were included in the study with 4 per dose group. Two patients dropped out after instillation 2 in dose groups 1 and 2. Overall, 88 instillations were administered without serious adverse events. There were 118 adverse events, of which 84 were related to the study drug. All adverse events were mild or moderate and number or severity was not correlated with dose group. Of the related adverse events 70% were confined to the genitourinary tract and resolved without intervention. There was a dose dependent systemic uptake with low plasma levels up to dose group 3 (0.2%, 100 mg). Maximum plasma concentration in dose group 4 (0.4%, 200 mg) was 71.7 ng/ml. This is below plasma concentrations of 123 and 128 ng/ml without significant side effects measured in healthy volunteers after subcutaneous (30 mg) or oral intake (100 mg) of imiquimod, respectively. CONCLUSIONSIntravesical treatment with TMX-101 is safe. The side effects are common but mild and mostly limited to the genitourinary tract. There is a low systemic uptake.
language: eng
source:
identifier: E-ISSN: 1527-3792 ; DOI: 1527-3792 ; DOI: 10.1016/j.juro.2012.11.150
fulltext: fulltext
issn:
  • 15273792
  • 1527-3792
url: Link


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titleResults of a phase 1 dose escalation study of intravesical TMX-101 in patients with nonmuscle invasive bladder cancer.
creatorFalke, Johannes ; Lammers, Rianne J M ; Arentsen, Harm C ; Ravic, Miroslav ; Pozzi, Raffaella ; Cornel, Erik B ; Vergunst, Henk ; de Reijke, Theo M ; Witjes, J Alfred
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subjectAdministration, Intravesical–Adverse Effects ; Adult–Pharmacokinetics ; Age Factors–Therapeutic Use ; Aged–Adverse Effects ; Aged, 80 and Over–Pharmacokinetics ; Aminoquinolines–Therapeutic Use ; Antineoplastic Agents–Drug Therapy ; Carcinoma, Transitional Cell–Mortality ; Cystoscopy–Pathology ; Disease-Free Survival–Methods ; Dose-Response Relationship, Drug–Methods ; Drug Administration Schedule–Pathology ; Female–Drug Therapy ; Follow-Up Studies–Mortality ; Humans–Pathology ; Male–Pathology ; Maximum Tolerated Dose–Pathology ; Middle Aged–Pathology ; Neoadjuvant Therapy–Pathology ; Neoplasm Invasiveness–Pathology ; Neoplasm Staging–Pathology ; Netherlands–Pathology ; Patient Safety–Pathology ; Prospective Studies–Pathology ; Risk Assessment–Pathology ; Sex Factors–Pathology ; Survival Rate–Pathology ; Treatment Outcome–Pathology ; Urinary Bladder Neoplasms–Pathology ; Abridged ; Aminoquinolines ; Antineoplastic Agents ; Imiquimod
descriptionPURPOSEImiquimod, a toll like receptor 7 (TLR-7) agonist, is effective as a topical treatment for skin malignancies. TMX-101 is a liquid formulation of imiquimod. In this study we establish a safety profile of TMX-101 in patients with nonmuscle invasive bladder cancer. MATERIALS AND METHODSWe conducted a multicenter phase 1 dose escalation study in patients with nonmuscle invasive bladder cancer. Patients were included in 1 of 4 dose groups (0.05%, 0.1%, 0.2% or 0.4%) and treated with 6 weekly instillations of TMX-101, starting 2 weeks after transurethral resection of bladder tumor. Patients were evaluated weekly, and pharmacokinetic and pharmacodynamic parameters were measured. RESULTSA total of 16 patients were included in the study with 4 per dose group. Two patients dropped out after instillation 2 in dose groups 1 and 2. Overall, 88 instillations were administered without serious adverse events. There were 118 adverse events, of which 84 were related to the study drug. All adverse events were mild or moderate and number or severity was not correlated with dose group. Of the related adverse events 70% were confined to the genitourinary tract and resolved without intervention. There was a dose dependent systemic uptake with low plasma levels up to dose group 3 (0.2%, 100 mg). Maximum plasma concentration in dose group 4 (0.4%, 200 mg) was 71.7 ng/ml. This is below plasma concentrations of 123 and 128 ng/ml without significant side effects measured in healthy volunteers after subcutaneous (30 mg) or oral intake (100 mg) of imiquimod, respectively. CONCLUSIONSIntravesical treatment with TMX-101 is safe. The side effects are common but mild and mostly limited to the genitourinary tract. There is a low systemic uptake.
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titleResults of a phase 1 dose escalation study of intravesical TMX-101 in patients with nonmuscle invasive bladder cancer.
descriptionPURPOSEImiquimod, a toll like receptor 7 (TLR-7) agonist, is effective as a topical treatment for skin malignancies. TMX-101 is a liquid formulation of imiquimod. In this study we establish a safety profile of TMX-101 in patients with nonmuscle invasive bladder cancer. MATERIALS AND METHODSWe conducted a multicenter phase 1 dose escalation study in patients with nonmuscle invasive bladder cancer. Patients were included in 1 of 4 dose groups (0.05%, 0.1%, 0.2% or 0.4%) and treated with 6 weekly instillations of TMX-101, starting 2 weeks after transurethral resection of bladder tumor. Patients were evaluated weekly, and pharmacokinetic and pharmacodynamic parameters were measured. RESULTSA total of 16 patients were included in the study with 4 per dose group. Two patients dropped out after instillation 2 in dose groups 1 and 2. Overall, 88 instillations were administered without serious adverse events. There were 118 adverse events, of which 84 were related to the study drug. All adverse events were mild or moderate and number or severity was not correlated with dose group. Of the related adverse events 70% were confined to the genitourinary tract and resolved without intervention. There was a dose dependent systemic uptake with low plasma levels up to dose group 3 (0.2%, 100 mg). Maximum plasma concentration in dose group 4 (0.4%, 200 mg) was 71.7 ng/ml. This is below plasma concentrations of 123 and 128 ng/ml without significant side effects measured in healthy volunteers after subcutaneous (30 mg) or oral intake (100 mg) of imiquimod, respectively. CONCLUSIONSIntravesical treatment with TMX-101 is safe. The side effects are common but mild and mostly limited to the genitourinary tract. There is a low systemic uptake.
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1Adult–Pharmacokinetics
2Age Factors–Therapeutic Use
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6Antineoplastic Agents–Drug Therapy
7Carcinoma, Transitional Cell–Mortality
8Cystoscopy–Pathology
9Disease-Free Survival–Methods
10Dose-Response Relationship, Drug–Methods
11Drug Administration Schedule–Pathology
12Female–Drug Therapy
13Follow-Up Studies–Mortality
14Humans–Pathology
15Male–Pathology
16Maximum Tolerated Dose–Pathology
17Middle Aged–Pathology
18Neoadjuvant Therapy–Pathology
19Neoplasm Invasiveness–Pathology
20Neoplasm Staging–Pathology
21Netherlands–Pathology
22Patient Safety–Pathology
23Prospective Studies–Pathology
24Risk Assessment–Pathology
25Sex Factors–Pathology
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titleResults of a phase 1 dose escalation study of intravesical TMX-101 in patients with nonmuscle invasive bladder cancer.
authorFalke, Johannes ; Lammers, Rianne J M ; Arentsen, Harm C ; Ravic, Miroslav ; Pozzi, Raffaella ; Cornel, Erik B ; Vergunst, Henk ; de Reijke, Theo M ; Witjes, J Alfred
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7Carcinoma, Transitional Cell–Mortality
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10Dose-Response Relationship, Drug–Methods
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12Female–Drug Therapy
13Follow-Up Studies–Mortality
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15Male–Pathology
16Maximum Tolerated Dose–Pathology
17Middle Aged–Pathology
18Neoadjuvant Therapy–Pathology
19Neoplasm Invasiveness–Pathology
20Neoplasm Staging–Pathology
21Netherlands–Pathology
22Patient Safety–Pathology
23Prospective Studies–Pathology
24Risk Assessment–Pathology
25Sex Factors–Pathology
26Survival Rate–Pathology
27Treatment Outcome–Pathology
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30Aminoquinolines
31Antineoplastic Agents
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abstractPURPOSEImiquimod, a toll like receptor 7 (TLR-7) agonist, is effective as a topical treatment for skin malignancies. TMX-101 is a liquid formulation of imiquimod. In this study we establish a safety profile of TMX-101 in patients with nonmuscle invasive bladder cancer. MATERIALS AND METHODSWe conducted a multicenter phase 1 dose escalation study in patients with nonmuscle invasive bladder cancer. Patients were included in 1 of 4 dose groups (0.05%, 0.1%, 0.2% or 0.4%) and treated with 6 weekly instillations of TMX-101, starting 2 weeks after transurethral resection of bladder tumor. Patients were evaluated weekly, and pharmacokinetic and pharmacodynamic parameters were measured. RESULTSA total of 16 patients were included in the study with 4 per dose group. Two patients dropped out after instillation 2 in dose groups 1 and 2. Overall, 88 instillations were administered without serious adverse events. There were 118 adverse events, of which 84 were related to the study drug. All adverse events were mild or moderate and number or severity was not correlated with dose group. Of the related adverse events 70% were confined to the genitourinary tract and resolved without intervention. There was a dose dependent systemic uptake with low plasma levels up to dose group 3 (0.2%, 100 mg). Maximum plasma concentration in dose group 4 (0.4%, 200 mg) was 71.7 ng/ml. This is below plasma concentrations of 123 and 128 ng/ml without significant side effects measured in healthy volunteers after subcutaneous (30 mg) or oral intake (100 mg) of imiquimod, respectively. CONCLUSIONSIntravesical treatment with TMX-101 is safe. The side effects are common but mild and mostly limited to the genitourinary tract. There is a low systemic uptake.
doi10.1016/j.juro.2012.11.150
urlhttp://search.proquest.com/docview/1350892117/
issn00225347
date2013-06-01