Intravesical Mycobacterial Cell Wall-DNA Complex in the Treatment of Carcinoma In Situ of the Bladder After Standard Intravesical Therapy Has Failed

Received 1 August 2008 published online 16 January 2009.

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Purpose

We assessed the clinical efficacy and safety of mycobacterial cell wall-DNA complex after intravesical administration in patients with carcinoma in situ in whom prior therapy with bacillus Calmette-Guerin failed or in those who were treatment naïve.

Materials and Methods

Patients received 6 weekly instillations of 4 or 8 mg mycobacterial cell wall-DNA complex (formulated as an emulsion) followed by 3 weekly instillations at weeks 12 and 24. Efficacy and safety were evaluated throughout the treatment phase and at months 12 and 18.

Results

A total of 55 patients (mean age 74 years, 74.6% male) received 4 mg (25) or 8 mg (30) mycobacterial cell wall-DNA complex emulsion. All patients were previously treated with bacillus Calmette-Guerin except for 8 who were treatment naïve and 2 who received chemotherapy. In the intent to treat population the complete response rate was 27.3% at weeks 12 and 26 in the 4 mg group while 46.4% of patients receiving 8 mg had a complete response at both points. Mycobacterial cell wall-DNA complex was well tolerated by both dose groups. Overall 90% of all adverse events were mild to moderate in severity.

Conclusions

Mycobacterial cell wall-DNA complex has shown antineoplastic activity in patients with bladder cancer with less toxicity than that associated with bacillus Calmette-Guerin administration. The tolerance and efficacy of mycobacterial cell wall-DNA complex might hold promise for the treatment of carcinoma in situ of the bladder.

Key Words: urinary bladder neoplasms, carcinoma in situ, mycobacterium, cell wall, administration, intravesical

Abbreviations and Acronyms: AE, adverse event, BCG, bacillus Calmette-Guerin, CIS, carcinoma in situ, EE, efficacy evaluable, ITT, intent to treat, MCC, mycobacterial cell wall-DNA complex, MCWE, mycobacterial cell wall extract, SAE, serious adverse event, UTI, urinary tract infection

a Queen's University, Kingston, Ontario, Canada

b Vancouver Island Health Authority, Victoria, British Columbia, Canada

c St. George Hospital, Kogarah, NSW, Australia

Correspondence: Department of Urology, Queen's University & Centre for Urological Research, 62 Barrie St., Kingston, Ontario K7L 3J7 Canada (telephone: 613-548-2424; FAX: 613-548-7836)

Study received research ethics committee approval from each participating site.

Supported by grants from Bioniche Life Sciences Inc (Belleville, Ontario, Canada).

For other articles on related topics see pages 1361, 1372 and 1381.

† Financial interest and/or other relationship with Bioniche, Solvay and Pierre Fabre.

PII: S0022-5347(08)03046-2

doi:10.1016/j.juro.2008.11.019

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