BACKGROUND: Chemotherapeutic anticancer properties are thought to derive from apoptosis pathway activation and/or cell division arrest, but animal models have also evidenced anti-angiogenic activity in some agents. PATIENTS AND METHODS: The impact of gemcitabine, irinotecan and oxaliplatin + 5-FU upon the serum markers vascular endothelial growth factor (VEGF) (pro-angiogenic) and IFN-gamma-inducible protein (IP)-10 (anti-angiogenic) was evaluated by ELISA in locally advanced and/or metastatic cancer versus clinical efficacy and survival. RESULTS: Patients had higher serum levels of both markers versus controls. No objective response to therapy was observed and no significant difference in either marker occurred during the first month of chemotherapy; analysis by survival showed slight transient VEGF decrease in longer survivors on day 14 and slight increase on day 28 in shorter survivors, who had baseline median IP-10 levels above longer survivors, diverging on day 14 (decrease and increase, respectively). Both groups were below baseline at day 28. Changes in IP-10 were not significant. CONCLUSION: These preliminary results provide a rationale for exploring whether continuous or frequent administration of some anti-neoplastic agents may elicit a global anti-angiogenic activity, and whether different administration schedules of the same drug could have a synergistic or an antagonistic effect, which obviously would need to be taken into account in determining combinations with new agents targeting angiogenesis.
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