Photodynamic therapy of ovarian cancer peritoneal metastasis with hexaminolevulinate: A toxicity study

• We studied the toxicity of PDT with hexaminolevulinate for the treatment of peritoneal carcinomatosis.
• Treatment was performed in a rat model.
• Treatment was effective but toxicity led to the death of rhabdomyolysis in almost all animals due to a lack of specificity of hexaminolevulinate for tumor nodules.
• This study highlights the fact that more specific photosensitizers need being developed so that PDT can safely treat peritoneal carcinomatosis.

SummaryContextWhile 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.MethodsPDT 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 8 h 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.ResultsPDT 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).ConclusionHAL 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.