title: What is the optimal regimen for BCG intravesical therapy? Are six weekly instillations necessary?
abstract: OBJECTIVE
  For more than 20 years, BCG intravesical therapy schedule has included 6 weekly instillations. Very few studies have, however, analyzed the rationale of this regimen. We previously demonstrated that intravesical BCG induced an increased peripheral immune response against mycobacterial antigens as compared to pretreatment values. In the present work, we have studied the weekly evolution of this immune response induced by intravesical BCG instillations.
  
  
  METHODS
  The evolution of the lymphoproliferative response of peripheral blood mononuclear cells against BCG culture filtrate (CF), tuberculin (PPD) and BCG extract (EXT) was tested before, every week during the BCG instillations and at 3 and 6 months follow-up in 9 patients with superficial bladder cancer treated with 6 weekly BCG instillations. Lymphoproliferation was measured by means of a tritiated thymidine incorporation test.
  
  
  RESULTS
  A significant increase in the lymphoproliferative response against PPD, CF and EXT was observed in 9, 8 and 7 of the 9 patients, respectively, as compared to pre-BCG values. The maximal lymphoproliferation was achieved after 4 instillations in 4/5 patients initially reactive against mycobacterial antigens whereas 2 of 4 initially nonreactive patients required 6 instillations. At 6 months' follow-up, lymphoproliferation against BCG and the other mycobacterial antigens returned to pre-BCG values in all patients. In 3 patients who received additional instillations because of tumor recurrence within 1 year of follow-up, the maximum immune response was observed already after 2 instillations.
  
  
  CONCLUSIONS
  In most patients, the maximal peripheral immune response is already observed after 4 weekly instillations. However, patients not previously immunized against mycobacterial antigens may require 6 weekly instillations to achieve a maximum stimulation level. Our data support the need to further evaluate the role of this status before starting BCG instillations. It could be of interest to study whether 6 BCG instillations are really necessary in patients previously immune against mycobacterial antigens.
authors.affiliation: Department of Urology, Erasme Hospital, University Clinics of Brussels, Belgium. azlotta@ulb.ac.be
authors.forename: A R
authors.initials: AR
authors.lastname: Zlotta
authors.forename: J P
authors.initials: JP
authors.lastname: van Vooren
authors.forename: K
authors.initials: K
authors.lastname: Huygen
authors.forename: A
authors.initials: A
authors.lastname: Drowart
authors.forename: M
authors.initials: M
authors.lastname: Decock
authors.forename: M
authors.initials: M
authors.lastname: Pirson
authors.forename: F
authors.initials: F
authors.lastname: Jurion
authors.forename: K
authors.initials: K
authors.lastname: Palfliet
authors.forename: O
authors.initials: O
authors.lastname: Denis
authors.forename: J
authors.initials: J
authors.lastname: Simon
authors.forename: C C
authors.initials: CC
authors.lastname: Schulman
mesh_terms: D000283:Administration, Intravesical; D000368:Aged; D000942:Antigens, Bacterial / Q000032:analysis; D001500:BCG Vaccine / Q000008:administration & dosage*; D002295:Carcinoma, Transitional Cell / Q000175:diagnosis / Q000276:immunology / Q000628:therapy*; D003558:Cystoscopy; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D009163:Mycobacterium bovis / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis / Q000276:immunology / Q000628:therapy*
chemical_list: D000942:Antigens, Bacterial; D001500:BCG Vaccine