Levamisole as an adjuvant to chemotherapy in extensive bronchogenic carcinoma. A veterans administration lung cancer group study

Abstract

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.

A Randomized Trial Comparing Cisplatin Plus 5-fluorouracil With or Without Levamisole in Operable Gastric Cancer

“…Levamisole was found to have a negative influence on survival in a multihospital randomized trial in patients with extensive lung cancer. The does-related toxicity of levamisole was also found to be significant 7 ) . The results from a large series of 720 patients with breast cancer showed that the patients with N+M0 disease developed a significantly higher recurrence rate after total mastectomy with partially axillary lymph node biopsy when levamisole was combined with radiotherapy 10 ) .…”

“…However, in this same study, when levamisole was combined with BCG, no advantage whatever was obtained and in a comparable melanoma’ adjuvant trial, Spittler et al found levamisole therapy to produce no advantage over placebo in either time to recurrence or survival 12 ) . In individual experiments with Moloney virus-induced rhabdomyosarcomas in BALB/c mice, levamisole treatmment seemed to be associated with an accelerated growth of the primary tumor, but this was not significant and even counter-balanced by a greater number of animals which showed inhibited tumor growth with levamisole 7 ) . The investigators, therefore, concluded that levamisole had no effect on the primary growth of these tumors.…”

“…Another study failed to show a beneficial effect of additional levamisole 7 ) . In an experimental model system of KHT sarcoma in mice, the addition of levamisole did not improve local tumor control.…”