Association of immune parameters with clinical outcome in stage III colon cancer: results of Southwest Oncology Group Protocol 9009 |
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| Authors: | Randall F Holcombe Joth Jacobson Shaker R Dakhil Ruby M Stewart Kenneth S Betzing Krishna Kannan John S Macdonald |
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| Institution: | (1) Division of Hematology/Oncology and Chao Family Comprehensive Cancer Center, University of California, Irvine Medical Center, Orange, Calif., USA, US;(2) Southwest Oncology Group Statistical Center, Seattle, Wash., USA, US;(3) Wichita CCOP, Wichita, Kan., USA, US;(4) Section of Hematology/Oncology and Center for Excellence in Cancer Research, Louisiana State University Medical Center – Shreveport, La., USA, US;(5) St. Vincent's Comprehensive Cancer Center, New York, N.Y., USA, VC |
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| Abstract: | 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.
Received: 9 July 1999 / Accepted: 11 August 1999 |
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| Keywords: | Levamisole Natural killer cells Lymphocyte phenotype Tumor immunology |
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