title: Phase I study of debulking surgery and photodynamic therapy for disseminated intraperitoneal tumors.
abstract: OBJECTIVE
  Phase I study designed to determine the maximum tolerated dose of intraoperative photodynamic therapy (PDT) at laparotomy/debulking surgery in patients with refractory or recurrent, disseminated intraperitoneal tumors.
  
  
  METHODS
  Patients received dihematoporphyrin ethers (DHE) 1.5-2.5 mg/kg by i.v. injection prior to surgery. Patients resected to < or = 5 mm of residual disease underwent laser light delivery to all peritoneal surfaces.
  
  
  RESULTS
  Fifty-four patients entered the study. Thirty-nine underwent resection and light delivery/PDT. PDT dose was escalated by increasing DHE from 1.5 to 2.5 mg/kg, shortening the interval between DHE injection and surgery from 72 to 48 hr, and increasing the light dose. Initially, 630 nm red light alone was used. In this group, PDT of 2.8-3.0 J/cm2 induced small bowel edema and resulted in 3 small bowel perforations after bowel resection or enterotomy. Further light dose escalation, however, was achieved by switching to less penetrating 514 nm green light to the bowel/mesentery. In later patients, whole peritoneal PDT was supplemented with boost doses of 10-15 J/cm2 red light or 5-7.5 J/cm2 green light to high risk areas. Small bowel complications were not seen after switching to less penetrating green light. Dose limiting toxicities occurred in 2 of 3 patients at the highest light dose of 5.0 J/cm2 green light with boost. These patients had pleural effusions that required thoracentesis and postoperative respiratory support for 7-9 days, while one had a gastric perforation. At potential follow-up times of 3.8-43.1 months (median 22.1 months), 30/39 patients are alive and 9/39 are free of disease.
  
  
  CONCLUSIONS
  The maximum tolerated dose of intraoperative PDT following debulking surgery performed 48 hr after intravenous administration 2.5 mg/kg DHE is 3.75 J/cm2 of 514 nm green light to the entire peritoneal surface with boosts to 5.0-7.5 J/cm2 of 514 nm green light or 10-15 J/cm2 of 630 nm red light to sites of gross disease encountered at surgery.
authors.affiliation: Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
authors.forename: T F
authors.initials: TF
authors.lastname: DeLaney
authors.forename: W F
authors.initials: WF
authors.lastname: Sindelar
authors.forename: Z
authors.initials: Z
authors.lastname: Tochner
authors.forename: P D
authors.initials: PD
authors.lastname: Smith
authors.forename: W S
authors.initials: WS
authors.lastname: Friauf
authors.forename: G
authors.initials: G
authors.lastname: Thomas
authors.forename: L
authors.initials: L
authors.lastname: Dachowski
authors.forename: J W
authors.initials: JW
authors.lastname: Cole
authors.forename: S M
authors.initials: SM
authors.lastname: Steinberg
authors.forename: E
authors.initials: E
authors.lastname: Glatstein
mesh_terms: D000328:Adult; D000368:Aged; D002277:Carcinoma / Q000188:drug therapy / Q000601:surgery / Q000628:therapy*; D003131:Combined Modality Therapy; D017323:Dihematoporphyrin Ether / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000601:surgery / Q000628:therapy*; D010534:Peritoneal Neoplasms / Q000188:drug therapy / Q000601:surgery / Q000628:therapy*; D010778:Photochemotherapy / Q000009:adverse effects; D012509:Sarcoma / Q000188:drug therapy / Q000601:surgery / Q000628:therapy*; D015996:Survival Rate
chemical_list: D017323:Dihematoporphyrin Ether