Levamisole/Fluorouracil

Chrisp, Paul; McTavish, Donna

doi:10.2165/00002512-199101040-00007

Drugs & Aging

1991

DOI: 10.2165/00002512-199101040-00007

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Levamisole/Fluorouracil

Paul Chrisp¹,

Donna McTavish²

Abstract: The combination of the antimetabolite fluorouracil plus the immunomodulator levamisole is used as adjuvant therapy following surgical tumour removal in patients with Dukes' stage C colon cancer. Fluorouracil given alone in this setting results in only a modest improvement in survival rate, and levamisole monotherapy is clinically ineffective. Well controlled studies, however, demonstrate that combined levamisole/fluorouracil reduces the recurrence rate by between 31 and 41% and the total mortality rate by betw… Show more

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1993

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Cited by 7 publications

References 57 publications

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Effect of levamisole on major histocompatibility complex class I expression in colorectal and breast carcinoma cell lines

Goodrich

Álvarez

Holcombe

1993

Cancer

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Background. The antihelminthic drug levamisole (LMS) is used in conjunction with 5‐fluorouracil (5‐FU) as adjuvant therapy to reduce the incidence of colon cancer relapse following surgical resection. Clinical trials in patients with breast cancer have yielded conflicting results as to its efficacy in the treatment of this malignancy. LMS is thought to act as an immunostimulant, yet its precise mechanism remains unclear. In this study, the effect of LMS on major histocompatibility complex (MHC) class I (MHC I) and MHC class II (MHC II) expressions in human colorectal and breast carcinoma cell lines was examined. Methods. The colon cancer cell line CaCo‐2 and the breast cancer cell line MDA‐MB‐435 were cultured for 24‐68 hours in the presence or absence of 10‐μ LMS followed by staining with antibodies directed against either MHC I or MHC II. After staining, cells were visualized by fluorescent microscopy. Results. When cultured in the presence of LMS, cells from both cell lines exhibited a decreased fluorescent intensity with antibodies directed against MHC I protein. The most significant difference from cells cultured without LMS was apparent after 48 hours of incubation. Neither cell line exhibited fluorescent intensities above background when stained with anti‐MHC II antibody. Conclusions. LMS decreases the expression of MHC I on CaCo‐2 and MDA‐MB‐435 tumor cell lines. Prior studies have indicated that natural killer (NK) cells are more efficient in attacking cells with lowered or no MHC I expression. An MHC I deficiency induced by LMS would augment NK‐mediated immune surveillance. One mechanism contributing to levamisole's anti‐tumor activity in vivo may be reduction of MHC I expression on tumor cells. Cancer 1993; 72:225–30.

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Effect of levamisole on major histocompatibility complex class I expression in colorectal and breast carcinoma cell lines

Goodrich

Álvarez

Holcombe

1993

Cancer

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Adverse effects of levamisole in cocaine users: a review and risk assessment

et al. 2017

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The immunomodulatory adjuvant and antihelminth levamisole is increasingly used as an adulterant in cocaine worldwide. An accumulating body of clinical and toxicological literature has appeared since 2010 describing neutropenia, agranulocytosis, leukoencephalopathy and vasculitis in cases associated with levamisole-adulterated cocaine. Mostly, neutropenia and agranulocytosis were reported, characterized by a decimation of neutrophils. A large proportion of cases also involved vasculopathy, characterized by pronounced black and purple skin purpura with cutaneous necrosis. Females are more susceptible for both agranulocytosis and vasculitis. Another complication reported with levamisole-adulterated cocaine is leukoencephalopathy, a disabling and potentially fatal neurological disorder caused by cerebral demyelination. In this review, all adverse effects associated with therapeutic levamisole and levamisole-adulterated cocaine are described. In addition, this review provides an update of the pharmacology of levamisole, its metabolism, including toxic metabolites and metabolites that are relevant for levamisole's addition to cocaine. Special emphasis is put on the immunopathology and the dose-effect relationship of chronic levamisole exposure. Finally, a risk assessment is provided based on the current level of levamisole adulteration in street cocaine, the dose range calculated per gram and the pattern of chronic exposure in heavy or dependent users.

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Association of immune parameters with clinical outcome in stage III colon cancer: results of Southwest Oncology Group Protocol 9009

Holcombe

Jacobson

Dakhil

et al. 1999

Cancer Immunology, Immunotherapy

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Levamisole (LMS), utilized in the adjuvant treatment of patients with stage III colon cancer, is immunomodulatory. To determine whether alterations in immune parameters before, during and after 12 months of 5FU/LMS therapy correlate with disease-free survival, 38 patients enrolled on Southwest Oncology Group (SWOG) protocol 8899 received extensive lymphocyte phenotypic analysis prior to therapy and 3, 6, 12 and 15 months after treatment initiation. The median follow-up of patients is 41 months. Significant increases in the proportion and total number of CD56+ natural killer cells were seen, starting at 3 months and continuing until 15 months (P < 0. 001). Increases in the total numbers of cells expressing CD25 (interleukin-2 receptor), VLA4 and the combinations of CD4: CD45RA and CD4:CDw29 were not evident during therapy but were seen at 15 months (P < 0.05: CD25, CD4:CDw29, CD4:CD45RA; P < 0.001: VLA4). Low levels of CD8+ cells prior to treatment initiation and after 3 months of therapy correlated with early relapse within the first year of 5FU/LMS treatment. Patients who have remained disease-free (n = 22, median follow-up 45 months) demonstrated increases in the total numbers of CD8+, CD25+, CD56+, VLA4+, CD4: CDw29 and CD4:CD45RA cells, primarily at 15 months. In contrast, patients who relapsed had decreased numbers of CD8+, CD4:CDw29, CD4: CD45RA and VLA4+ cells and minimal increases in CD56+ and CD25+ cells. Statistically significant differences between the late-relapse group and the group remaining disease-free were seen for CD25+, CD4: CD45RA and CD4:CDw29 cells at the 15-month assay time (P = 0.0276, P = 0.0349, P = 0.0178 respectively). In conclusion, multiple alterations in lymphocyte phenotype, with increases in the proportion and total number of cells involved in cell-mediated immune responses, were seen during and especially following completion of therapy with 5FU/LMS. Many of these changes are significantly associated with clinical outcome and may be useful for risk stratification of stage III colon cancer patients following completion of adjuvant therapy.

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Levamisole/Fluorouracil

Cited by 7 publications

References 57 publications

Effect of levamisole on major histocompatibility complex class I expression in colorectal and breast carcinoma cell lines

Effect of levamisole on major histocompatibility complex class I expression in colorectal and breast carcinoma cell lines

Adverse effects of levamisole in cocaine users: a review and risk assessment

Association of immune parameters with clinical outcome in stage III colon cancer: results of Southwest Oncology Group Protocol 9009

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