Levamisole as an adjuvant to chemotherapy in extensive bronchogenic carcinoma: a Veterans Administration Lung Cancer Group Study.

A randomized trial of 381 patients with extensive lung cancer compared immunochemotherapy with levamisole (150 mg/m2 orally three times a week), cyclophosphamide (700 mg/m2 IV every three weeks) and CCNU (70 mg/m2 orally every six weeks) with the same chemotherapy without levamisole. When disease progressed, doxorubicin hydrochloride or doxorubicin hydrochloride plus levamisole was used. Hematologic toxicity required reduction of the levamisole dosage to 2.5 mg/kg (100 mg/m2) three times a week, every other week. When corrections are made for all variables, levamisole itself had a negative influence on survival. Patients given 150 mg/m2 had a shorter median time to treatment failure (P = 0.02), lower response rate (P = 0.02) more toxicity (P = 0.08), and shorter median survival (P = 0.08). Patients with 10% or greater weight loss had significantly shorter survival (P = 0.006). The regimen with the reduced dosage of levamisole also was more toxic (P = 0.05) but otherwise did not differ from the control regimen. The cause of the adverse effect of levamisole is unknown. It did not occur because of an excess of toxic deaths or because smaller doses of cytotoxic drugs were given to patients treated with levamisole. Neither the initial lymphocyte count nor the Candida skin test reactions had a significant effect on the study endpoints when correction was made for dominant prognostic factors such as the initial performance status and weight loss.