Phase I study of iv administration of methanol extraction residue of bacillus Calmette-Guerin

Four weekly iv doses, ranging from 10 to 640 μg/m², of the methanol extraction residue of bacillus Calmette-Guerin (MER) were given to 22 patients with advanced cancer in an effort to determine a maximum tolerated dose. Fever and chills for 24-48 hours were common at doses >80 μg/m² but were prolonged for 3 days to 9 weeks at 640 μg/m². While moderate decreases in pulmonary vital capacity decreased consistently only at higher doses. However, no roentgenographic changes suggestive of multiple lung granulomas were observed, such as were produced in dogs and mice by iv administration of MER. Autopsy failed to reveal granulomas in three patients. There were no objective tumor responses, nor were consistent changes observed in blood counts or skin tests to recall antigens. MER can be given iv with acceptable acute toxicity in doses up to 640 μg/m², at which point fever may be unduly prolonged. Patients given MER iv must be followed carefully for the development of interstitial pneumonitis.