Jametta Magwood

Background

Levamisole is a pharmaceutical with anthelminthic and immunomodulatory properties that received approval from the Food and Drug Administration in 1991 as part of adjuvant chemotherapy regimens for colorectal cancer. The addition of levamisole to 5-flouroruacil (5-FU) was first evaluated by the North Central Cancer Treatment Group in a 3-arm clinical trial that found that 5-FUlevamisole for 12 months was superior to either surgery alone or surgery followed by levamisole alone (recurrence rate was reduced by 40% and the death rate by 33% in Dukes’ C colon cancer).1 A subsequent trial intergroup trial randomized patients with Dukes’ B2 and C colon cancer to surgery alone or 1 year of adjuvant levamisole or 5FUlevamisole and confirmed the efficacy of 5FUlevamisole with respect to disease free survival and overall survival.2 As a result, adjuvant chemotherapy became the standard for stage III colon cancer as reported by an National Cancer Institute consensus development panel.3 Subsequently, primarily because of toxicity reasons, leucovorin replaced levamisole in most adjuvant chemotheraoy regimens for stage III colorectal cancer. Clinical toxicity of levamisole was noted as early as 1976 when several cases of leukopenia and agranulocytosis were reported. Recurrence with re-exposure was well described and agranulocytosis spontaneously reversed upon discontinuation of therapy. Vasculitis secondary to levamisole treatment was first reported in 1978, presenting primarily as leukocytoclastic vasculitis, cutaneous necrotising vasculitis and thrombotic vasculopathy without vasculitis. These findings typically, but not invariably, involve the ear lobes. In the early 1990s, levamisole became unavailable for human use in the United States due to toxicity concerns. Various neurological side effects were described with levamisole therapy, the most concerning complication being multifocal inflammatory leukoencephalopathy. Recently, several persons have developed a novel syndrome characterized by necrotic noses and ears, leg ulcers, agranulocytosis, thrombovasculopathy, and positive antineutrophil cytoplasmic antibodies (ANCAs) as a result of the drug cocaine being adulterated with levamisole. We describe the drug below.

Background

Levamisole is a pharmaceutical with anthelminthic and immunomodulatory properties that received approval from the Food and Drug Administration in 1991 as part of adjuvant chemotherapy regimens for colorectal cancer. The addition of levamisole to 5-flouroruacil (5-FU) was first evaluated by the North Central Cancer Treatment Group in a 3-arm clinical trial that found that 5-FUlevamisole for 12 months was superior to either surgery alone or surgery followed by levamisole alone (recurrence rate was reduced by 40% and the death rate by 33% in Dukes’ C colon cancer).1 A subsequent trial intergroup trial randomized patients with Dukes’ B2 and C colon cancer to surgery alone or 1 year of adjuvant levamisole or 5FUlevamisole and confirmed the efficacy of 5FUlevamisole with respect to disease free survival and overall survival.2 As a result, adjuvant chemotherapy became the standard for stage III colon cancer as reported by an National Cancer Institute consensus development panel.3 Subsequently, primarily because of toxicity reasons, leucovorin replaced levamisole in most adjuvant chemotheraoy regimens for stage III colorectal cancer. Clinical toxicity of levamisole was noted as early as 1976 when several cases of leukopenia and agranulocytosis were reported. Recurrence with re-exposure was well described and agranulocytosis spontaneously reversed upon discontinuation of therapy. Vasculitis secondary to levamisole treatment was first reported in 1978, presenting primarily as leukocytoclastic vasculitis, cutaneous necrotising vasculitis and thrombotic vasculopathy without vasculitis. These findings typically, but not invariably, involve the ear lobes. In the early 1990s, levamisole became unavailable for human use in the United States due to toxicity concerns. Various neurological side effects were described with levamisole therapy, the most concerning complication being multifocal inflammatory leukoencephalopathy. Recently, several persons have developed a novel syndrome characterized by necrotic noses and ears, leg ulcers, agranulocytosis, thrombovasculopathy, and positive antineutrophil cytoplasmic antibodies (ANCAs) as a result of the drug cocaine being adulterated with levamisole. We describe the drug below.

Background

Levamisole is a pharmaceutical with anthelminthic and immunomodulatory properties that received approval from the Food and Drug Administration in 1991 as part of adjuvant chemotherapy regimens for colorectal cancer. The addition of levamisole to 5-flouroruacil (5-FU) was first evaluated by the North Central Cancer Treatment Group in a 3-arm clinical trial that found that 5-FUlevamisole for 12 months was superior to either surgery alone or surgery followed by levamisole alone (recurrence rate was reduced by 40% and the death rate by 33% in Dukes’ C colon cancer).1 A subsequent trial intergroup trial randomized patients with Dukes’ B2 and C colon cancer to surgery alone or 1 year of adjuvant levamisole or 5FUlevamisole and confirmed the efficacy of 5FUlevamisole with respect to disease free survival and overall survival.2 As a result, adjuvant chemotherapy became the standard for stage III colon cancer as reported by an National Cancer Institute consensus development panel.3 Subsequently, primarily because of toxicity reasons, leucovorin replaced levamisole in most adjuvant chemotheraoy regimens for stage III colorectal cancer. Clinical toxicity of levamisole was noted as early as 1976 when several cases of leukopenia and agranulocytosis were reported. Recurrence with re-exposure was well described and agranulocytosis spontaneously reversed upon discontinuation of therapy. Vasculitis secondary to levamisole treatment was first reported in 1978, presenting primarily as leukocytoclastic vasculitis, cutaneous necrotising vasculitis and thrombotic vasculopathy without vasculitis. These findings typically, but not invariably, involve the ear lobes. In the early 1990s, levamisole became unavailable for human use in the United States due to toxicity concerns. Various neurological side effects were described with levamisole therapy, the most concerning complication being multifocal inflammatory leukoencephalopathy. Recently, several persons have developed a novel syndrome characterized by necrotic noses and ears, leg ulcers, agranulocytosis, thrombovasculopathy, and positive antineutrophil cytoplasmic antibodies (ANCAs) as a result of the drug cocaine being adulterated with levamisole. We describe the drug below.