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

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 co rrelate with disease-free survival, 38 patients enrolled on Southwest Oncol ogy Group (SWOG) protocol 8899 received extensive lymphocyte phenotypic ana lysis prior to therapy and 3, 6, 12 and 15 months after treatment initiatio n. 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), VLA 4 and the combinations of CD4: C3D45RA and CD4:CDw29 were not evident durin g therapy but were seen at 15 months (P < 0.05. CD25, CD3:CDw29, CD4:CD45RA ; P < 0.001: VLA4). Low levels of CD8(+) cells prior to treatment initiatio n and after 3 months of therapy correlated with early relapse within the fi rst year of 5FU/LMS treatment. Patients who have remained disease-free (n = 22, median followup 45 months) demonstrated increases in the total numbers of CD8(+), CD25(+), CD56(+), VLA4(+), CD4: CDw29 and CD4:CD45RA cells, pri marily at 15 rrmonths.In contrast, patients who relapsed had decreased numb ers of CD8(+), CD4:CDw29, CD4: CD35RA and VLA4(+) cells and minimal increas es in CD56(+) and CD25(+) cells. Statistically significant differences betw een the late-relapse group and the group remaining disease-free were seen f or 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 alte rations in lymphocyte phenotype, with increases in the proportion and total number of cells involved in cell-mediated immune responses, were seen duri ng and especially following completion of therapy with 5FU/LMS, Many of the se changes ars-significantly associated with clinical outcome and may be us eful for risk stratification of stage III colon cancer patients following c ompletion of adjuvant therapy.