Clinical and immunologic results of a phase II trial of sequential imiquimod and photodynamic therapy for vulval intraepithelial neoplasia.

2.50
Hdl Handle:
http://hdl.handle.net/10541/68066
Title:
Clinical and immunologic results of a phase II trial of sequential imiquimod and photodynamic therapy for vulval intraepithelial neoplasia.
Authors:
Winters, Ursula; Daayana, Sai; Lear, John T; Tomlinson, Anne E; Elkord, Eyad; Stern, Peter L; Kitchener, Henry C
Abstract:
PURPOSE: High-risk human papillomavirus (HPV)-associated vulval intraepithelial neoplasia (VIN) is difficult to treat by excision or ablation because of high recurrence rates. Small studies of photodynamic therapy (PDT) and imiquimod treatments have shown some success and function at least in part through stimulation of local immune responses. Indeed, there is evidence that immunosuppressed individuals have higher rates of VIN, suggesting immune control is relevant. EXPERIMENTAL DESIGN: In the study, 20 women with high-grade VIN were treated with topical imiquimod and the PDT sequentially. Vulval biopsy and blood were taken pretreatment and, after imiquimod and PDT, with follow up for 1 year. Clinical response was assessed by measuring lesion size. Biopsies were analyzed for HPV DNA and tumor-infiltrating lymphocytes including T regulatory cells. RESULTS: The treatment was well-tolerated. There was an overall response rate of 55% by intention treat and 64% per protocol. The 52-week symptom response was 65% asymptomatic, compared with 5% at baseline. The nonresponders showed a significantly higher level of T regulatory cells in the lesions after imiquimod treatment. CONCLUSIONS: The response rates are clinically relevant, and the treatment regimen was feasible for the majority. Initial nonresponders to imiquimod seem to be relatively refractory, and this may derive from their unfavorable local immune environment, in particular, the increased proportions of T regulatory cells, possibly the limiting action and/or development of any HPV T-cell immunity. The potential benefit of this treatment is its ability to treat multifocal disease.
Affiliation:
School of Cancer and Imaging, University of Manchester, St. Mary's Hospital, Immunology Group, Paterson Institute for Cancer Research, University of Manchester, Manchester, United Kingdom.
Citation:
Clinical and immunologic results of a phase II trial of sequential imiquimod and photodynamic therapy for vulval intraepithelial neoplasia. 2008, 14 (16):5292-9 Clin. Cancer Res.
Journal:
Clinical Cancer Research
Issue Date:
15-Aug-2008
URI:
http://hdl.handle.net/10541/68066
DOI:
10.1158/1078-0432.CCR-07-4760
PubMed ID:
18698049
Type:
Article
Language:
en
ISSN:
1078-0432
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorWinters, Ursula-
dc.contributor.authorDaayana, Sai-
dc.contributor.authorLear, John T-
dc.contributor.authorTomlinson, Anne E-
dc.contributor.authorElkord, Eyad-
dc.contributor.authorStern, Peter L-
dc.contributor.authorKitchener, Henry C-
dc.date.accessioned2009-05-13T16:12:56Z-
dc.date.available2009-05-13T16:12:56Z-
dc.date.issued2008-08-15-
dc.identifier.citationClinical and immunologic results of a phase II trial of sequential imiquimod and photodynamic therapy for vulval intraepithelial neoplasia. 2008, 14 (16):5292-9 Clin. Cancer Res.en
dc.identifier.issn1078-0432-
dc.identifier.pmid18698049-
dc.identifier.doi10.1158/1078-0432.CCR-07-4760-
dc.identifier.urihttp://hdl.handle.net/10541/68066-
dc.description.abstractPURPOSE: High-risk human papillomavirus (HPV)-associated vulval intraepithelial neoplasia (VIN) is difficult to treat by excision or ablation because of high recurrence rates. Small studies of photodynamic therapy (PDT) and imiquimod treatments have shown some success and function at least in part through stimulation of local immune responses. Indeed, there is evidence that immunosuppressed individuals have higher rates of VIN, suggesting immune control is relevant. EXPERIMENTAL DESIGN: In the study, 20 women with high-grade VIN were treated with topical imiquimod and the PDT sequentially. Vulval biopsy and blood were taken pretreatment and, after imiquimod and PDT, with follow up for 1 year. Clinical response was assessed by measuring lesion size. Biopsies were analyzed for HPV DNA and tumor-infiltrating lymphocytes including T regulatory cells. RESULTS: The treatment was well-tolerated. There was an overall response rate of 55% by intention treat and 64% per protocol. The 52-week symptom response was 65% asymptomatic, compared with 5% at baseline. The nonresponders showed a significantly higher level of T regulatory cells in the lesions after imiquimod treatment. CONCLUSIONS: The response rates are clinically relevant, and the treatment regimen was feasible for the majority. Initial nonresponders to imiquimod seem to be relatively refractory, and this may derive from their unfavorable local immune environment, in particular, the increased proportions of T regulatory cells, possibly the limiting action and/or development of any HPV T-cell immunity. The potential benefit of this treatment is its ability to treat multifocal disease.en
dc.language.isoenen
dc.subjectVulvar Canceren
dc.subject.meshAdministration, Topical-
dc.subject.meshAdult-
dc.subject.meshAminoquinolines-
dc.subject.meshAntigens, CD-
dc.subject.meshAntineoplastic Agents-
dc.subject.meshCarcinoma in Situ-
dc.subject.meshCombined Modality Therapy-
dc.subject.meshFemale-
dc.subject.meshFluorescent Antibody Technique-
dc.subject.meshHumans-
dc.subject.meshImmunohistochemistry-
dc.subject.meshLymphocytes, Tumor-Infiltrating-
dc.subject.meshMiddle Aged-
dc.subject.meshPhotochemotherapy-
dc.subject.meshT-Lymphocytes, Regulatory-
dc.subject.meshVulvar Neoplasms-
dc.titleClinical and immunologic results of a phase II trial of sequential imiquimod and photodynamic therapy for vulval intraepithelial neoplasia.en
dc.typeArticleen
dc.contributor.departmentSchool of Cancer and Imaging, University of Manchester, St. Mary's Hospital, Immunology Group, Paterson Institute for Cancer Research, University of Manchester, Manchester, United Kingdom.en
dc.identifier.journalClinical Cancer Researchen

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