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环境病理学,毒理学和肿瘤学期刊
影响因子: 1.241 5年影响因子: 1.349 SJR: 0.356 SNIP: 0.613 CiteScore™: 1.61

ISSN 打印: 0731-8898
ISSN 在线: 2162-6537

环境病理学,毒理学和肿瘤学期刊

DOI: 10.1615/JEnvironPatholToxicolOncol.v25.i1-2.230
pages 373-388

Updated Results of a Phase I Trial of Motexafin Lutetium-Mediated Interstitial Photodynamic Therapy in Patients with Locally Recurrent Prostate Cancer

Kosmas Verigos
Department of Radiation Oncology, University of Pennsylvania, 3400 Spruce Street, 2 Donner, Philadelphia, PA 19104
Diana C. Hsiung Stripp
Department of Radiation Oncology, University of Pennsylvania, 3400 Spruce Street, 2 Donner, Philadelphia, PA 19104
Rosemarie Mick
Department of Biostatistics and Epidemiology, University of Pennsylvania, 3400 Spruce Street, 2 Donner, Philadelphia, PA 19104
Timothy C. Zhu
Department of Radiation Oncology, University of Pennsylvania, 3400 Spruce Street, 2 Donner, Philadelphia, PA 19104
Richard Whittington
Department of Radiation Oncology, University of Pennsylvania, 3400 Spruce Street, 2 Donner, Philadelphia, PA 19104
Debbie Smith
Department of Radiation Oncology, Department of Urology, University of Pennsylvania, 3400 Spruce Street, 2 Donner, Philadelphia, PA 19104
Andreea Dimofte
Department of Radiation Oncology, University of Pennsylvania, 3400 Spruce Street, 2 Donner, Philadelphia, PA 19104
Jarod Finlay
Department of Radiation Oncology, University of Pennsylvania, 3400 Spruce Street, 2 Donner, Philadelphia, PA 19104
Theresa M. Busch
Department of Radiation Oncology, University of Pennsylvania, 3400 Spruce Street, 2 Donner, Philadelphia, PA 19104
Zelig A. Tochner
Department of Radiation Oncology, University of Pennsylvania, 3400 Spruce Street, 2 Donner, Philadelphia, PA 19104
S. Bruce Malkowicz
Department of Urology, University of Pennsylvania, 3400 Spruce Street, 2 Donner, Philadelphia, PA 19104
Eli Glatstein
Department of Radiation Oncology, University of Pennsylvania, 3400 Spruce Street, 2 Donner, Philadelphia, PA 19104
Stephen M. Hahn
Department of Radiation Oncology, University of Pennsylvania, 3400 Spruce Street, 2 Donner, Philadelphia, PA 19104

ABSTRACT

Locally recurrent prostate cancer after treatment with radiation therapy is a clinical problem with few acceptable treatments. One potential treatment, photodynamic therapy (PDT), is a modality that uses laser light, drug photosensitizer, and oxygen to kill tumor cells through direct cellular cytotoxicity and/or through destruction of tumor vasculature. A Phase I trial of interstitial PDT with the photosensitizer Motexafin lutetium was initiated in men with locally recurrent prostate cancer. In this ongoing trial, the primary objective is to determine the maximally tolerated dose of Motexafin lutetium-mediated PDT. Other objectives include evaluation of Motexafin lutetium uptake from prostate tissue using a spectrofluorometric assay and evaluation of optical properties in the human prostate. Fifteen men with biopsy-proven locally recurrent prostate cancer and no evidence of distant metastatic disease have been enrolled and 14 have been treated. Treatment plans were developed using transrectal ultrasound images. The PDT dose was escalated by increasing the Motexafin lutetium dose, increasing the 732 ran light dose, and decreasing the drug-light interval. Motexafin lutetium doses ranged from 0.5 to 2 mg/kg administered IV 24, 6, or 3 hr prior to 732 ran light delivery. The light dose, measured in real time with in situ spherical detectors was 25−100 J/cm2. Light was delivered via optical fibers inserted through a transperineal brachytherapy template in the operating room. Optical property measurements were made before and after light therapy. Prostate biopsies were obtained before and after light delivery for spectrofluorometric measurements of photosensitizer uptake. Fourteen patients have completed protocol treatment on eight dose levels without dose-limiting toxicity. Grade I genitourinary symptoms that are PDT related have been observed. One patient had Grade II urinary urgency that was urinary catheter related. No rectal or other gastrointestinal PDT-related tox-icities have been observed to date. Measurements of Motexafin lutetium demonstrated the presence of photosensitizer in prostate tissue from all patients. Optical property measurements demonstrated substantial heterogeneity in the optical properties of the human prostate gland which supports the use of individualized treatment planning for prostate PDT.


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