Circulating vascular endothelial growth factor and interferon-gamma-inducible protein-10 levels in pancreatic cancer during chemotherapy.
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.


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.


CONCLUSIONS
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.
Bellone
Graziella
G
Department of Clinical Physiopathology, University of Turin, Italy. graziella.bellone@unito.it
Novarino
Anna
A
Chiappino
Isabella
I
Gramigni
Claudia
C
Carbone
Anna
A
Addeo
Alfredo
A
Tonel
Elena
E
Bertetto
Oscar
O
Emanuelli
Giorgio
G
D000230:Adenocarcinoma / Q000097:blood* / Q000098:blood supply / Q000188:drug therapy; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000097:blood*; D018592:Cross-Over Studies; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004797:Enzyme-Linked Immunosorbent Assay; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D000077146:Irinotecan; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D010190:Pancreatic Neoplasms / Q000097:blood* / Q000098:blood supply / Q000188:drug therapy; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*; D000093542:Gemcitabine
D020533:Angiogenesis Inhibitors; C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D009944:Organoplatinum Compounds; D042461:Vascular Endothelial Growth Factor A; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin; D000093542:Gemcitabine