Clinical studies of methanol extraction residue fraction of Bacillus Calmette-Guérin as an immunostimulant in patients with advanced cancer.

Forty patients with advanced gastrointestinal cancer, all previous chemotherapy failures, were treated with a methanol extraction residue of Bacillus Calmette-Guérin (MER) alone, administered intradermally in either weekly or every-4-week schedules. The only significant side effect was local cutaneous reaction ranging from papules through pustules to draining ulcerations. On the weekly schedule these reactions frequently reached a point of clinical intolerability. In spite of the advanced nature of their disease, 29% of the patients had increased reactivity to recall antigens; 57% showed an increased reaction to dinitrochlorobenzene challenge during MER therapy; 38% had significant increases in lymphocyte blastogenesis to phytohemagglutinin mitogen, 48% to concanavalin A, and 43% to pokeweed mitogen. Increases (greater than 25%) in immunoglobulins A, M, and G were also observed in 31, 41, and 28% of patients, respectively. MER therapy was associated with increased thymus-derived (T) and bone marrow-derived (B) cells and an increased ratio of T-cells to B-cells. Increases in those determinants reflecting cellular immunity (skin tests, phytohemagglutinin and concanavalin A blastogenesis, and T-cells) showed a positive correlation with patient survival. Increases in those determinants associated with humoral immunity (pokeweed mitogen blastogenesis, immunoglobulins, and B-cells) had, if anything, a negative survival correlation. In comparing administration schedules, the weekly method produced more frequent increases in dinitrochlorobenzene response, more rapid increases with higher peaks in lymphocyte blastogenesis transformation, and more frequent increases in circulating T- and B-cells. The every-4-week method was associated with significantly greater frequencies of increases in immunoglobulins A and M. Of 36 patients with measurable disease, 3 showed greater than 50% objective responses, 2 showed a 25 to 50% response, and 1 showed a mixed response. MER is a potent simulus to cellular and humoral immunity in the patient with advanced gastrointestinal cancer. This stimulation may occasionally result in a clinically evident antineoplastic effect.