title: Toxicities and early outcomes in a phase 1 trial of photodynamic therapy for premalignant and early stage head and neck tumors.
abstract: OBJECTIVE
  Management of early superficial lesions in the head and neck remains complex. We performed a phase 1 trial for high-grade premalignant and early superficial lesions of the head and neck using photodynamic therapy (PDT) with Levulan (ALA).
  
  
  METHODS
  Thirty-five subjects with high grade dysplasia, carcinoma in situ, or microinvasive (⩽1.5mm depth) squamous cell carcinoma were enrolled. Cohorts of 3-6 patients were given escalating intraoperative light doses of 50-200J/cm(2) 4-6h after oral administration of 60mg/kg ALA. Light at 629-635nm was delivered in a continuous (unfractionated) or fractionated (two-part) schema.
  
  
  RESULTS
  PDT was delivered to 30/35 subjects, with 29 evaluable. There was one death possibly due to the treatment. The regimen was otherwise tolerable, with a 52% rate of grade 3 mucositis which healed within several weeks. Other toxicities were generally grade 1 or 2, including odynophagia (one grade 4), voice alteration (one grade 3), and photosensitivity reactions. One patient developed grade 5 sepsis. With a median follow-up of 42months, 10 patients (34%) developed local recurrence; 4 of these received 50J/cm(2) and two each received 100, 150, and 200J/cm(2). Ten (34%) patients developed recurrence adjacent to the treated field. There was a 69% complete response rate at 3months.
  
  
  CONCLUSIONS
  ALA-PDT is well tolerated. Maximum Tolerated Dose appears to be higher than the highest dose used in this study. Longer followup is required to analyze effect of light dose on local recurrence. High marginal recurrence rates suggest use of larger treatment fields.
authors: Department of Radiation Oncology, University of Pennsylvania, 3400 Civic Center Blvd, Philadelphia, PA 19104, United States. Electronic address: peter.ahn@uphs.upenn.edu.
authors: Peter H
authors: PH
authors: Ahn
authors: Department of Radiation Oncology, University of Pennsylvania, 3400 Civic Center Blvd, Philadelphia, PA 19104, United States; Department of Radiation Oncology, Johns Hopkins University, 401 N. Broadway, Baltimore, MA 21231, United States.
authors: Harry
authors: H
authors: Quon
authors: Department of Otolaryngology-Head and Neck Surgery, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, United States.
authors: Bert W
authors: BW
authors: O'Malley
authors: Department of Otolaryngology-Head and Neck Surgery, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, United States.
authors: Gregory
authors: G
authors: Weinstein
authors: Department of Otolaryngology-Head and Neck Surgery, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, United States.
authors: Ara
authors: A
authors: Chalian
authors: Department of Otolaryngology-Head and Neck Surgery, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, United States; Department of Otolaryngology, University of Michigan, 1500 E. Medical Center Dr, Ann Arbor, MI 48109, United States.
authors: Kelly
authors: K
authors: Malloy
authors: Department of Anesthesiology, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, United States.
authors: Joshua H
authors: JH
authors: Atkins
authors: Department of Oral Medicine, University of Pennsylvania, 3400 Civic Center Blvd, Philadelphia, PA 19104, United States.
authors: Thomas
authors: T
authors: Sollecito
authors: Department of Oral Medicine, University of Pennsylvania, 3400 Civic Center Blvd, Philadelphia, PA 19104, United States.
authors: Martin
authors: M
authors: Greenberg
authors: Department of Radiation Oncology, University of Pennsylvania, 3400 Civic Center Blvd, Philadelphia, PA 19104, United States.
authors: Sally
authors: S
authors: McNulty
authors: Department of Radiation Oncology, University of Pennsylvania, 3400 Civic Center Blvd, Philadelphia, PA 19104, United States.
authors: Alexander
authors: A
authors: Lin
authors: Department of Radiation Oncology, University of Pennsylvania, 3400 Civic Center Blvd, Philadelphia, PA 19104, United States.
authors: Timothy C
authors: TC
authors: Zhu
authors: Department of Radiation Oncology, University of Pennsylvania, 3400 Civic Center Blvd, Philadelphia, PA 19104, United States.
authors: Jarod C
authors: JC
authors: Finlay
authors: Department of Radiation Oncology, University of Pennsylvania, 3400 Civic Center Blvd, Philadelphia, PA 19104, United States.
authors: Keith
authors: K
authors: Cengel
authors: Department of Pathology, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, United States.
authors: Virginia
authors: V
authors: Livolsi
authors: Department of Pathology, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, United States.
authors: Michael
authors: M
authors: Feldman
authors: Department of Biostatistics and Epidemiology, University of Pennsylvania, 423 Guardian Drive, Philadelphia, PA 19104, United States.
authors: Rosemarie
authors: R
authors: Mick
authors: Department of Radiation Oncology, University of Pennsylvania, 3400 Civic Center Blvd, Philadelphia, PA 19104, United States.
authors: Theresa M
authors: TM
authors: Busch
mesh_terms: D000368:Aged; D000622:Aminolevulinic Acid / Q000009:adverse effects*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010778:Photochemotherapy / Q000009:adverse effects* / Q000379:methods; D017319:Photosensitizing Agents / Q000009:adverse effects*; D011230:Precancerous Conditions / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D017319:Photosensitizing Agents; D000622:Aminolevulinic Acid
keywords: ALA; Aminolevulinic acid; Carcinoma in situ; Head and neck cancer; Levulan; PDT; Photodynamic therapy; Protoporphyrin IX; Severe dysplasia