PHOTODYNAMIC THERAPY USING 5-AMINOLEVULINIC ACID FOR EXPERIMENTAL PANCREATIC-CANCER - PROLONGED ANIMAL SURVIVAL

Experimental studies have been carried out using 5-aminolaevulinic aci d (ALA) to induce transient porphyrin photosensitisation for photodyna mic therapy (PDT) in a pancreatic cancer model in Syrian golden hamste rs. ALA was given either intravenously or orally (in bolus or fraction ated doses) with the laser light delivered by means of a bare fibre to uching the tissue surface or external irradiation using a light-integr ating cylindrical applicator. Animals were killed 1-24 h after ALA adm inistration for pharmacokinetic studies and 3-7 days after light expos ure to study PDT-induced necrosis. A separate survival study was also performed after a fractionated oral dose of ALA and external irradiati on. Protoporphyrin IX sensitisation in the tumour tissue as measured b y quantitative fluorescence microscopy was highest after intravenous a dministration of 200 mg kg(-1) ALA and then in decreasing order after oral fractionated and oral bolus doses (both 400 mg kg(-1)). Laser lig ht application al 630 nm to give 12-50 J from the bare fibre or 50 J c m(-2) using surface illumination with the cylindrical applicator resul ted in tumour necrosis up to 8 mm in depth. In larger tumours a rim of viable tumour was observed on the side opposite to illumination. In a randomised study, survival of treated animals was significantly longe r than in the untreated control group (log-rank test, P < 0.02), altho ugh all animals died of recurrent tumour. This technique shows promise in the treatment of small volumes of tumour in the pancreas.