Mycobacterial cell wall extract for treatment of carcinoma in situ of the bladder

Purpose. Bacillus Calmette-Guerin (BCG) established immunotherapy as an eff ective modality for carcinoma in situ of the bladder and remains the most e ffective agent for treatment. However, as a live organism it has the potent ial for undesirable side effects and toxicity. This result has led to the s earch for other active and safer biological response modifiers. We investig ated the efficacy of a mycobacterial cell wall extract (MCWE) from Mycobact erium phlei, which does not contain live bacteria, for management of carcin oma in situ of the bladder in humans. Materials and Methods: The requirement for an emulsified preparation was in vestigated with photon correlation spectroscopy to determine the stability of the bacterial fragments. A total of 61 patients with histologically docu mented carcinoma in situ completed the study. Cell wall extract from M. phl ei suspended in oil droplets to form an emulsion were instilled into the bl adder at a dose of 4 mg. once weekly for 6 weeks and then monthly for 1 yea r. Response assessment was performed at 3-month intervals. Complete respons e to treatment indicated the absence of endoscopic and histological evidenc e of carcinoma in situ. Partial responders were those cases in which cystos copy and biopsies were negative but cytology was suspicious for malignant c ells. All other cases were considered failures. Results: The need for an emulsified suspension of the cell wall extract was confirmed by the demonstration that the cell wall extract alone in urine a ggregated, whereas the MCWE emulsion had remained stable. Kaplan-Meier esti mates showed negative cystoscopy and biopsies in 62.5% at 12, 49.3% at 24 a nd 41.1% of patients at 60 weeks after therapy. After this point the number of responders had remained stable. Excellent tolerance with minimal toxici ty was observed. Conclusions: Our study demonstrates clinical activity of low doses of MCWE against human bladder cancer. The results observed at the dosage used in ou r trial are less than those observed with live BCG. However, MCWE has a bet ter toxicity profile and can be instilled in the presence of a disrupted ur othelium. It also appears to exhibit activity in patients in whom BCG has f ailed.