Phase I toxicity study of methanol-extracted residue of bacillus Calmette-Guerin by the iv route

Sixty-four adult patients with a variety of disseminated malignant diseases received methanol-extracted residue (MER) of bacillus Calmette-Guerin (BCG) by the iv route in doses that ranged from 0.1 to 1.25 mg/m ². Forty patients received iv MER alone weekly and 24 patients received MER combined with chemotherapy weekly. The number of doses given to each patient ranged from one to 18, with a mean number of doses of 2.3. Fever, invariably occurring at doses of >0.5 mg/m ², began around 3-6 hours with defervescence usually within 24 hours but lasting as long as 5 days. Chills, malaise, nausea and/or vomiting, and headaches were frequent side effects independent of dose. The large majority of patients had a good tolerance necessitating only symptomatic therapy. No difference in toxicity was found between the two groups analyzed. Eleven patients (17.2%) had more serious toxic effects; eight patients (13.7%) developed bilateral pulmonary infiltrates after one to 18 doses suggestive of granulomatous disease. This was not dose-related but correlated with history of prior BCG treatment or presence of a positive PPD skin test. The abnormality resolved spontaneously upon discontinuation of MER, usually within 4-6 weeks. There was one case of acute urticaria reaction controlled with antihistaminics. There was also one case each of acute erythrodermic rash and bullous dermatosis with acute vasculitis in the skin controlled with oral glucocorticoids. There were no major life-threatening toxic reactions and no long-term morbidity induced by iv MER. No definite tumor responses were documented. It appears that iv MER is a safe modality of treatment which should be investigated in phase II trials. The dose should be reduced in patients with a history of prior BCG or a positive PPD skin test. A dose of 0.1 mg is recommended for these patients and a dose of 0.5 mg/m ² is recommended for the others.