Photodynamic therapy of ovarian cancer peritoneal metastasis with hexaminolevulinate: a toxicity study.
BACKGROUND
While photodynamic therapy (PDT) is a promising treatment for peritoneal carcinomatosis, its use is often limited because of the toxicity of photosensitizers. In this study, safety of PDT with hexaminoevulinate (HAL), a second generation photosensitizer, is assessed.


METHODS
PDT of the peritoneal cavity was performed in a rat model of peritoneal carcinomatosis. Rats were treated according to different protocols: with full or half HAL dose, after intraperitoneal or oral administration of HAL, 4 or 8h after its injection, using red or green light, after protection of the liver or cooling of the abdominal wall. Toxicity was assessed by blood tests quantifying hematocrit, liver and muscular enzymes and by pathological examination of abdominal and intrathoracic organs after treatment. The results were analyzed in the light of quantification of fluorescence and protoporphyrin IX (PPIX) content of the same organs.


RESULTS
PDT with HAL induced rhabdomyolysis, intestinal necrosis and liver function test anomalies, leading to death in 2 out of 34 rats. The liver and the intestine contained high levels of PPIX (3-5 times more than tumor nodules).


CONCLUSIONS
HAL PDT lacked specificity. However, the strategy associating diagnosis, treatment and evaluation of the results in one single procedure was effective and should be tested with other photosensitizers.
Department of Gynaecology and Obstetrics, Lille University Hospital, Lille, France; INSERM U703, Univ Lille Nord de France, Lille University Hospital, Lille, France.
Laurie
L
Guyon
Centre de biologie-pathologie, Lille University Hospital, Lille, France.
Marie-Odile
MO
Farine
INSERM U703, Univ Lille Nord de France, Lille University Hospital, Lille, France.
Jean Claude
JC
Lesage
Centre de biologie-pathologie, Lille University Hospital, Lille, France.
Anne-Marie
AM
Gevaert
Centre Français des Porphyries, Hôpital Louis Mourier, Colombes, France; INSERM U773, Paris Diderot University, Paris, France.
Sylvie
S
Simonin
Centre Français des Porphyries, Hôpital Louis Mourier, Colombes, France; INSERM U773, Paris Diderot University, Paris, France.
Caroline
C
Schmitt
Department of Gynaecology and Obstetrics, Lille University Hospital, Lille, France; INSERM U703, Univ Lille Nord de France, Lille University Hospital, Lille, France.
Pierre
P
Collinet
INSERM U703, Univ Lille Nord de France, Lille University Hospital, Lille, France; GDR 3049 Médicaments Photoactivables - Photochimiothérapie (PHOTOMED), France. Electronic address: serge.mordon@inserm.fr.
Serge
S
Mordon
D000622:Aminolevulinic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D045744:Cell Line, Tumor; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D007263:Infusions, Parenteral; D007410:Intestinal Diseases / Q000139:chemically induced* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary*; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000627:therapeutic use; D051381:Rats; D011916:Rats, Inbred F344; D012206:Rhabdomyolysis / Q000139:chemically induced* / Q000473:pathology; D016896:Treatment Outcome
D017319:Photosensitizing Agents; D000622:Aminolevulinic Acid; C419924:5-aminolevulinic acid hexyl ester
Light dosimetry; Peritoneal carcinomatosis treatment; Photobleaching; Photodynamic therapy safety; Second generation photosensitizer