Urinary interleukin-8 predicts the response of standard and low dose intravesical bacillus Calmette-Guerin (modified Danish 1331 strain) for superficial bladder cancer.
OBJECTIVE
We determined whether the proinflammatory cytokine interleukin-8 (IL-8) can serve as a predictor for the response to standard (120 mg.) and low (40 mg.) dose intravesical bacillus Calmette-Guerin (BCG) (modified Danish 1331 strain) for managing superficial bladder cancer in patients at risk for recurrence and progression.


METHODS
We randomized 26 patients with superficial bladder cancer to receive a 6-week course of standard dose 120 mg. or low dose 40 mg. intravesical BCG. Voided urine samples were collected immediately before and after (2 and 4 hours) BCG instillation. Urine samples were centrifuged at 1,500 rpm for 8 minutes and stored at -80C. IL-8 was measured using a commercial enzyme-linked immunosorbent assay. Patients were monitored for recurrence, progression and side effects of BCG treatment at 3-month intervals.


RESULTS
At a median followup of 24 months (range 12 to 30), 5 and 6 patients who received a standard and low dose, respectively had disease recurrence and/or progression (nonresponders). At 4 hours after BCG mean Il-8 levels plus or minus SD were significantly higher in responders than in nonresponders (1,099.33 +/- 708.51 versus 261.82 +/- 182.66 pg./ml., p = 0.001). There was no difference at 4 hours in mean IL-8 levels in the standard and low dose groups (596.92 +/- 546 and 893 +/- 798.67 pg./ml., respectively, p = 0.28). In all patients who remained disease-free IL-8 levels were greater than 400 pg./ml. In 9 of the 11 patients with disease recurrence/progression IL-8 levels were less than 400 pg./ml.


CONCLUSIONS
IL-8 secretion after the initial intravesical BCG instillation strongly correlates with the possibility of future recurrence/progression. The quantitative IL-8 response to low and standard dose intravesical BCG (Danish 1331) is similar.
Kumar
Anant
A
Department of Urology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
Dubey
Deepak
D
Bansal
Pradeep
P
Mandhani
Anil
A
Naik
Sita
S
D001500:BCG Vaccine / Q000008:administration & dosage* / Q000009:adverse effects; D002278:Carcinoma in Situ / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007194:India; D016209:Interleukin-8 / Q000652:urine*; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000276:immunology / Q000473:pathology; D009367:Neoplasm Staging; D011230:Precancerous Conditions / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D011446:Prospective Studies; D016896:Treatment Outcome; D001743:Urinary Bladder / Q000187:drug effects / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology
D001500:BCG Vaccine; D016209:Interleukin-8