Angiogenesis modifications related with cetuximab plus irinotecan as anticancer treatment in advanced colorectal cancer patients.
BACKGROUND
Angiogenesis has been correlated with increased invasion and metastases in a variety of human neoplasms. Inadequate inhibition of the growth of tumor microvessels by anticancer agents may result in treatment failure, rated clinically as progressive or stable disease. We designed this trial to investigate the modification of the vascular endothelial growth factor (VEGF) and interferon-gamma (IFN-gamma) in advanced colorectal cancer patients during treatment with a weekly combination of cetuximab plus irinotecan.


METHODS
Forty-five metastatic colorectal cancer patients were prospectively evaluated for circulating levels of VEGF and IFN-gamma during the treatment with cetuximab (initial dose of 400 mg/m(2), followed by weekly infusions of 250 mg/m(2)) plus weekly irinotecan (90 mg/m(2)). The circulating levels of the cytokines were assessed at the following time points: just before and at 1, 21, 50 and 92 days after the start of cetuximab plus irinotecan treatment.


RESULTS
Basal serum VEGF median levels were significantly decreased just at the first day (after the first treatment infusion (P = 0.016). The VEGF persisted at the following time points reaching the highest statistical significance 92 days after the first infusion (P < 0.0001). On the contrary, IFN-gamma values showed a statistical significant increase one day after the first infusion (P < 0.0001). This effect persisted 21 days after the treatment start (P = 0.001), but was no more evident at the following time points. Moreover, a linear regression model with variance analysis showed a significant negative correlation between VEGF and IFN-gamma values 1, 21 and 50 days after the treatment beginning (P = 0.002, 0.001 and 0.047, respectively).


CONCLUSIONS
This study suggests that a cetuximab may induce a modulation of VEGF circulating levels. The reduction of VEGF serum levels is a sudden and long lasting phenomenon. Moreover, in our study we identified a IFN-gamma increase, even if the specific role of this behavior remains to be investigated.
Vincenzi
B
B
Medical Oncology, University Campus Bio-Medico, Rome, Italy.
Santini
D
D
Russo
A
A
Silletta
M
M
Gavasci
M
M
Battistoni
F
F
Di Cuonzo
G
G
Rocci
L
L
Gebbia
N
N
Tonini
G
G
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000098:blood supply / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000097:blood*; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000097:blood / Q000188:drug therapy*; D011446:Prospective Studies; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000077146:Irinotecan; D007371:Interferon-gamma; D000068818:Cetuximab; D002166:Camptothecin