Levamisole and surgery in bronchial carcinoma patients: increase in deaths from cardiorespiratory failure.

Abstract

Life table analysis of early entry to this randomised blind trial of 318 patients has shown a significantly poorer survival for resected lung cancer patients treated with levamisole for three days before operation and three days a fortnight thereafter than for placebo-treated controls. This excess was largely due to deaths that had been attributed to operation or other causes (non-cancer deaths), most occurring in the six weeks after operation. In the 99 resected patients treated with levamisole there was a 15% excess of deaths in this category, compared with the placebo-treated controls. Extensive analysis excluded maldistribution of patients between the groups as a cause of this difference.Many more died in respiratory distress, mostly without clear cause, in the levamisole group. Antibody (lgG) reacting with myocardial sarcolemma or sarcoplasm was found in the only serum samples available for testing which were drawn from patients during the syndrome. The findings are in keeping with a primary effect on the heart, possibly involving an autoimmune mechanism. The effect has not been noted in other trials.

Immunotherapy of Lung Cancer

“…In the other study, Anthony and colleagues adjusted the dose to body weight and found no difference between the levamisole and control groups. 7 This 49 study actually showed an increase in deaths due to cardiorespiratory disease in the patients treated with levamisole.…”

“…In the study by Anthony and associates there were an inordinate number of cardiorespiratory deaths in patients treated with levamisole. 7 However, an extensive effort in Europe and the United States to confirm toxicity of the agent failed to confirm these findings. 6 Willoughby and Wood reviewed a variety of side effects of levamisole and found that treatment had been stopped in less than 5 percent of patients because of adverse reactions.…”

Blood groups and the response to immunotherapy

“…Palliative Rh-negative patients showed a similar effect. Differential response to immunotherapy by blood group could have implications for the interpretation of immunotherapy trials.We have reported that excess post-operative deaths in levamisole-treated lung cancer patients were more frequent in patients who were blood group 0 and/or Rh (D)-negative [3]. The excess deaths were due to cardiorespiratory failure and were associated (in the only cases where serum samples were available for testing) with the presence of antimyocardial antibodies that were not detected in any patient without the syndrome.…”

The Role of Adjuvant Therapy in the Surgical Treatment of Lung Cancer

“…Analyses performed excluding noncancer deaths from both groups showed no advantage or disadvantage from levamisole. 2 Work in animal tumor models suggests that direct intralesional BCG followed by resection of the tumor and regional lymph nodes will provide systemic antitumor immunity capable of eradicating artificially induced metastatic disease. The in-vestigation of Holmes, which included twenty-seven patients who had resection of the tumor, two to four weeks following percutaneous intralesional injection of BCG, showed 85 percent of the lung cancer patients and 58 percent of the group with pulmonary metastasis alive and well at a median followup time for the series of sixteen months.…”