Photodynamic therapy with 3-(1'-hexyloxyethyl) pyropheophorbide a for cancer of the oral cavity.

Abstract

PURPOSE:

The primary objective was to evaluate safety of 3-(1'-hexyloxyethyl)pyropheophorbide-a (HPPH) photodynamic therapy (HPPH-PDT) for dysplasia and early squamous cell carcinoma of the head and neck (HNSCC). Secondary objectives were the assessment of treatment response and reporters for an effective PDT reaction.

EXPERIMENTAL DESIGN:

Patients with histologically proven oral dysplasia, carcinoma in situ, or early-stage HNSCC were enrolled in two sequentially conducted dose escalation studies with an expanded cohort at the highest dose level. These studies used an HPPH dose of 4 mg/m(2) and light doses from 50 to 140 J/cm(2). Pathologic tumor responses were assessed at 3 months. Clinical follow up range was 5 to 40 months. PDT induced cross-linking of STAT3 were assessed as potential indicators of PDT effective reaction.

RESULTS:

Forty patients received HPPH-PDT. Common adverse events were pain and treatment site edema. Biopsy proven complete response rates were 46% for dysplasia and carcinoma in situ and 82% for squamous cell carcinomas (SCC) lesions at 140 J/cm(2). The responses in the carcinoma in situ/dysplasia cohort are not durable. The PDT-induced STAT3 cross-links is significantly higher (P = 0.0033) in SCC than in carcinoma in situ/dysplasia for all light doses.

CONCLUSION:

HPPH-PDT is safe for the treatment of carcinoma in situ/dysplasia and early-stage cancer of the oral cavity. Early-stage oral HNSCC seems to respond better to HPPH-PDT in comparison with premalignant lesions. The degree of STAT3 cross-linking is a significant reporter to evaluate HPPH-PDT-mediated photoreaction.

• Authors: Nestor Rigual, Gal Shafirstein, Michele T Cooper, Heinz Baumann, David A Bellnier, Ulas Sunar, Erin C Tracy, Daniel J Rohrbach, Gregory Wilding, Wei Tan, Maureen Sullivan, Mihai Merzianu, Barbara W Henderson
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 19 Issue 23 Pg. 6605-13 (Dec 01 2013) ISSN: 1557-3265 [Electronic] United States
• PMID: 24088736 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, N.I.H., Extramural)
• Copyright: ©2013 AACR.

Chemical References

• Photosensitizing Agents
• STAT3 Transcription Factor
• STAT3 protein, human
• Chlorophyll
• 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a

Topics

• Adult
• Aged
• Aged, 80 and over
• Carcinoma, Squamous Cell (drug therapy, metabolism, mortality, pathology)
• Chlorophyll (analogs & derivatives, pharmacokinetics, therapeutic use)
• Disease-Free Survival
• Female
• Humans
• Male
• Middle Aged
• Mouth Neoplasms (drug therapy, metabolism, mortality, pathology)
• Photochemotherapy
• Photosensitizing Agents (pharmacokinetics, therapeutic use)
• STAT3 Transcription Factor (metabolism)
• Tissue Distribution
• Treatment Outcome