Levamisole Toxicity

To the Editor: Levamisole use will no doubt increase following the recent report by Laurie et al and the National Cancer Institute (NCI) Clinical Alert both related to the use of levamisole/fluorouracil (5-FU) as adjuvant treatment for colon cancer. Toxicity of levamisole is generally described as mild with nausea, diarrhea, and leukopenia being the most significant adverse effects with fatigue, dermatitis, and stomatitis also seen. Depsite the generally mild nature of the toxicity, occasional patients experience enough side effects to cause discontinuation of therapy. We report a patient with an unusual levamisole toxicity that resulted in discontinuation of the drug. A 47-year-old woman with node-positive colon cancer agreed to randomization in a clinical trial (EST 2284, Intergroup-0035) evaluating levamisole versus levamisole with 5-FU. She received levamisole 50 mg orally three times a day every 2 weeks and 5-FU 450 mg/m2 weekly. In the fifth month of treatment, she experienced the onset of bilateral arm pain occurring late in the first day of levamisole and resolving by 24 hours after the last dose. These symptoms also occurred with the next course of levamisole. Clinical examination showed upper arm pain with aching and stiffness in the wrists and fingers. Forearm muscles were tender, but there was no joint inflammation. There was no fever, rash, mucositis, leukopenia, or eosinophilia. The erythrocyte sedimentation rate was 8 mm/hr, creatine kinase 31 U/L, and antinuclear antibodies less than 1:20. The next course of levamisole resulted in similar but more severe pain with significant disruption of the patient's work as a florist. 5-FU alone was continued with no recurrence of these symptoms. Three years later the patient is well without pain or evidence for recurrent tumor. This symptom complex is clearly related to the levamisole treatment and might be considered a variant of the "flu-like" symptoms reported in other levamisole trials. We suggest that clinicians using levamisole in randomized trials or without the NCI Group C mechanism be aware of the wide spectrum of toxicities that may be seen with this interesting drug for the purpose of pretreatment discussion with patients and for the monitoring of therapy. The last sentence of the letter-to-the-editor entitled "Levamisole Toxicity" by Drs Leonard DeLorenza and James A. Stewart, published in the February 1990 issue (J Clin Oncol 8:365, 1990) contained an error. The sentence should have read: "We suggest that clinicians using levamisole in randomized trials or within the NCI Group C mechanism be aware of the wide spectrum of toxicities that may be seen with this interesting drug for the purpose of pretreatment discussion with patients and for the monitoring of therapy."