For colorectal cancer, it is recommended that carcinoembryonic antigen (CEA) be ordered preoperatively, if it would assist in staging and surgical planning. Postoperative CEA levels should be performed every 3 months for stage II and III disease for at least 3 years if the patient is a potential candidate for surgery or chemotherapy of metastatic disease. CEA is the marker of choice for monitoring the response of metastatic disease to systemic therapy. Data are insufficient to recommend the routine use of p53, ras, thymidine synthase, dihydropyrimidine dehydrogenase, thymidine phosphorylase, microsatellite instability, 18q loss of heterozygosity, or deleted in colon cancer (DCC) protein in the management of patients with colorectal cancer. For pancreatic cancer, CA 19-9 can be measured every 1 to 3 months for patients with locally advanced or metastatic disease receiving active therapy. Elevations in serial CA 19-9 determinations suggest progressive disease but confirmation with other studies should be sought. New markers and new evidence to support the use of the currently reviewed markers will be evaluated in future updates of these guidelines.

Effects of gemcitabine (Gemzar) on immune cells were examined in pancreas cancer patients to determine whether it was immunosuppressive, or potentially could be combined with vaccines or other immunotherapy to enhance patient's responses to their tumors. Blood was obtained at five time-points, before therapy, 3-4 days after initial gemcitabine infusion and immediately preceding three additional weekly infusions. Effects on T-cell subsets, B-cells, myeloid dendritic cell precursors, antigen presenting cells (APC), activated/memory, and naive cells were examined. Functional activity was measured by intracellular staining for cytokines before and after T-cell activation, and by interferon gamma production in EliSpot responses to tumor presentation. Although absolute lymphocyte counts decreased with the initial treatment with gemcitabine infusion, the counts stabilized during subsequent treatments, then returned within normal ranges seven days after the fourth treatment so that the absolute lymphocyte count no longer differed significantly from that prior to treatment. These effects on absolute lymphocyte counts were mirrored by statistically significant decreases in absolute numbers of CD3 and CD20 lymphocytes during these time periods. The proportions of T and B-cells, however did not change significantly with therapy, although significance changes were observed in some specialized subsets. A decrease in the proportions of the major BDCA-1+, CD1b myeloid dendritic cell subset and a reciprocal increase in the minor BDCA-3+ dendritic cell subsets resulted at 3-4 days, then their levels returned to normal. No significant changes in percentages of CD86 and CD80 APCs or CD4+, CD25+ T-cells were documented. Increased percentages of CD3+, CD45RO+ memory lymphocytes reached significance at day 7, then declined to statistically significant decrease at days 14 and 21 after the second and third infusions, respectively. Immune T-cells were functional in pancreas cancer patients treated with gemcitabine. The data suggest that gemcitabine therapy may decrease memory T-cells and promote naive T-cell activation. We conclude that gemcitabine therapy (1) is not immunosuppressive and (2) may enhance responses to specific vaccines or immunotherapy administered to activate or support immune responses directed toward driving effector immunity to cancer cells.

When all randomized patients were evaluated, no significant clinical benefit was seen with ASI in surgically resected colon cancer patients with stage II or III colon cancer. However, there was an indication that treatment compliance with effective immunization results in disease-free and overall survival benefits.