Photodynamic therapy for gastrointestinal tumors using three photosensitizers--ALA induced PPIX, Photofrin and MTHPC. A pilot study.
Photodynamic therapy (PDT) produces localized necrosis with light after prior administration of a photosensitizing drug. As PDT lesions in the gastrointestinal tract heal well, the technique is suitable for repeated endoscopic use. In this study we used PDT to treat benign and malignant gastrointestinal tumors in esophagus, duodenum and rectum in 22 patients, who refused or were not suitable for surgery. Patients were sensitized with 0.15 mg/kg of body weight with mesotetrahydroxyphenylchlorin i.v. m-THPc (2 patients), with 2.0 mg/kg Photofrin i.v. (4 patients) or 60 mg/kg 5-aminolevulinic acid orally ALA (which is converted in vivo to active derivate protoporphyrin IX-PRIX) in fractionated doses (16 patients). Laser treatment was performed 2 days after Photofrin, 2 and 4 days after mTHPc and 4 hours after ALA, using a metal vapour laser (628 nm, 50-150 J/cm2 for ALA and Photofrin, 650 nm and 10-15 J/cm2 for mTHPc). Using ALA, the necrosis was only superficial (up to 1.8 mm depth). Four patients treated with Photofrin showed deeper necrosis, in one case of 8 mm colon cancer complete response, in three cases 1-1.5 cm adenomatous polyps involving the ampulla Vateri 50% longer term reduction in size-seen endoscopically. Two patients with rectal villous adenomas treated with mTHPc showed 60-80% reduction in size (observed endoscopically) within few days after PDT, with better effects for treatment carried out 4 rather than 2 days after the sensitization. In all patients the healing was without any complications. Photofrin and mTHPc work better, but cause cutaneous photosensitivity lasting 12 and 5 weeks, respectively. Better results with ALA are possible when using higher drug doses or modified light dosimetry. PDT is a promising treatment for small localized tumors in patients unsuitable for surgery, but further work is required to optimize the treatment conditions.
Department of Gastroenterology, St. Elisabeth Oncological Institute, Bratislava, Slovakia.
P
P
Mĺkvy
H
H
Messmann
J
J
Regula
M
M
Conio
M
M
Pauer
C E
CE
Millson
A J
AJ
MacRobert
S G
SG
Bown
D000328:Adult; D000368:Aged; D000622:Aminolevulinic Acid / Q000627:therapeutic use; D017323:Dihematoporphyrin Ether / Q000627:therapeutic use; D004379:Duodenal Neoplasms / Q000188:drug therapy; D004938:Esophageal Neoplasms / Q000188:drug therapy; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy*; D006801:Humans; D007834:Lasers; D008297:Male; D008652:Mesoporphyrins / Q000627:therapeutic use; D008875:Middle Aged; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D010865:Pilot Projects; D011355:Prodrugs / Q000627:therapeutic use; D011524:Protoporphyrins / Q000627:therapeutic use; D012004:Rectal Neoplasms / Q000188:drug therapy
D008652:Mesoporphyrins; D017319:Photosensitizing Agents; D011355:Prodrugs; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; D017323:Dihematoporphyrin Ether; C028025:protoporphyrin IX; C072269:temoporfin