title: The effect of isoniazid on BCG-induced toxicity in patients with superficial bladder cancer.
abstract: The use of bacillus Calmette-Guérin in the treatment of transitional cell cancer of the bladder has caused concern because of its associated adverse effects. We conducted a randomized prospective, double-blind, multicentre study to determine whether isoniazid prophylaxis could reduce BCG-induced toxicity without compromising its immunotherapeutic effects. Patients (n = 160) with histologically documented urothelial cancer (pTa-T1, pTis, G1-3) were treated with 6 weekly instillations of BCG Connaught strain, 81 mg, administered concomitantly with a 3-day course of isoniazid (300 mg o.d.) or placebo. Side-effects were recorded with each treatment and at follow-up. Of the patients treated with isoniazid, 19% remained free from side-effects, compared with 16% of the placebo group. Local side-effects confined to the bladder were significantly lower among those receiving isoniazid (35% vs. 48%, p < 0.01). Local side-effects together with systemic adverse effects such as fever, nausea or skin rash were experienced by 30% of patients in each arm. There were no differences in tumour recurrence between the two patient groups. Concomitant isoniazid reduces the local, but not the systemic side-effects of topically applied BCG without compromising the antitumour effect on superficial, transitional cell cancer of the bladder during a follow-up period that now exceeds 2 years.
authors.affiliation: Department and Sections of Urology, University Hospitals of Lund, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Al Khalifa
authors.forename: P
authors.initials: P
authors.lastname: Elfving
authors.forename: W
authors.initials: W
authors.lastname: Månsson
authors.forename: S
authors.initials: S
authors.lastname: Colleen
authors.forename: S
authors.initials: S
authors.lastname: Hellsten
authors.forename: M
authors.initials: M
authors.lastname: Duchek
authors.forename: G
authors.initials: G
authors.lastname: Nyberg
authors.forename: P
authors.initials: P
authors.lastname: Callaghan
authors.forename: C
authors.initials: C
authors.lastname: Rademark
authors.forename: R
authors.initials: R
authors.lastname: Eriksson
authors.forename: R
authors.initials: R
authors.lastname: Olsson
authors.forename: G
authors.initials: G
authors.lastname: Hagberg
authors.forename: C E
authors.initials: CE
authors.lastname: Nelson
mesh_terms: D000283:Administration, Intravesical; D000368:Aged; D000995:Antitubercular Agents / Q000627:therapeutic use*; D001500:BCG Vaccine / Q000008:administration & dosage / Q000009:adverse effects*; D002278:Carcinoma in Situ / Q000628:therapy*; D002295:Carcinoma, Transitional Cell / Q000628:therapy*; D004311:Double-Blind Method; D005076:Exanthema / Q000139:chemically induced / Q000517:prevention & control; D005260:Female; D005334:Fever / Q000139:chemically induced / Q000517:prevention & control; D006801:Humans; D007538:Isoniazid / Q000627:therapeutic use*; D008297:Male; D009325:Nausea / Q000139:chemically induced / Q000517:prevention & control; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018709:Statistics, Nonparametric; D001745:Urinary Bladder Diseases / Q000209:etiology* / Q000517:prevention & control*; D001749:Urinary Bladder Neoplasms / Q000628:therapy*
chemical_list: D000995:Antitubercular Agents; D001500:BCG Vaccine; D007538:Isoniazid