Early clinical experience with 5‐aminolevulinic acid for the photodynamic therapy of superficial bladder cancer

Abstract

Objective To report clinical experience with intravesical instillations of 5‐aminolevulinic acid (ALA) for the photodynamic therapy of superficial bladder cancer and to assess any side‐effects of the treatment. Patients and methods Ten patients (six men and four women, mean age 62.3 years, range 42–73) with refractory superficial bladder cancer were treated with photodynamic therapy using 5 g of ALA dissolved in 30 mL sodium bicarbonate instilled intravesically. After a mean retention of 5.1 h, the bladder interior was illuminated transurethrally at radiation integrals of 15, 30 or 60 J/cm2 . At integrals of 15 or 30 J/cm2 red light (635 nm) was used and at 60 J/cm2 , green light (514 nm, 40 J/cm2 ) was combined with a subsequent application of red light (635 nm, 20 J/cm2 ). Results After 10–12 weeks, four patients had a complete remission, two a partial remission, there was no change in three and one had progressive disease. Of those patients responding, the bladder was preserved in five after a mean follow‐up of 15 months (range 6–27). There were no photodermatoses or bladder shrinkage in any patient. Conclusions Photodynamic therapy with intravesically applied ALA is effective in destroying superficial urothelial carcinomas of the bladder. There were no serious side‐effects which could preclude further clinical testing.

Photodetection of early human bladder cancer based on the fluorescence of 5-aminolaevulinic acid hexylester-induced protoporphyrin IX: a pilot study

“…Confirmed by histopathological examination, we have demonstrated that the fluorescence of PpIX in the urothelium induced by intravesically administered h-ALA correlated significantly with neoplastic lesions and was suitable for the detection of papillary tumours as well as for dysplasia and carcinoma in situ. The 7% rate of false negative responses found in the present study is comparable to the value given by Jichlinski et al in 1997 and slightly higher than that presented by the Munich group (Kriegmair et al, 1996). A total number of 28 biopsies were taken from areas proven to be benign.…”

“…Only five of these samples revealed an enhanced red fluorescence under violet light irradiation, yielding a rate of falsely positive fluorescence findings of 17%. This result seems to be quite small compared to both the results of Kriegmair et al (1996) and Jichlinski et al (1997). But it may be explained by the small number of biopsies taken, or the fact that the fluorescence induced by the long-chain esters was found to be limited to the site of application (Peng et al, 1996), hence no supplementary PpIX build-up from systemic ALA uptake is observed.…”

“…However, the twofold increase of PpIX fluorescence after 6 h in neoplastic tissues by using h-ALA may further enhance the PDT effect as compared to the use of ALA. The latter appeared insufficient as observed in recent studies (Kriegmair et al, 1996).…”

“…This technique has been shown to work, among other applications, in urology, where easy instillation in the bladder, combined with the fact that this organ is readily accessible endoscopically, makes it an ideal object. Alongside classical techniques such as cytology or white light examination, fluorescence PD by ALA-induced PpIX provides some advantages (Leveckis et al, 1994;Kriegmair et al, 1996;Jichlinski et al, 1997). This inspection modality allows an exact mapping which pinpoints, with a high level of sensitivity and specificity, the locations of carcinoma in situ (CIS) as well as early stages of cancer-like dysplasias, which are normally difficult to recognize under white light examination.…”

The influence of hypoxia and pH on aminolaevulinic acid-induced photodynamic therapy in bladder cancer cells in vitro

“…Aminolaevulinic acid (ALA) is currently undergoing clinical trials as a means of inducing photosensitization for PDT of bladder (Kriegmair et al, 1996) and skin cancers (Cairnduff et al, 1994). It is well established that photodynamic toxicity using haematoporphyrin derivative (HPD) can be almost completely abolished by hypoxia.…”