Circulating VEGF reduction, response and outcome in advanced colorectal cancer patients treated with cetuximab plus irinotecan.
OBJECTIVE
We designed this trial to investigate if modifications in levels of circulating vascular endothelial growth factor (VEGF) may be related to clinical response and outcome in advanced colorectal cancer patients during treatment with a weekly combination of cetuximab plus irinotecan.


METHODS
A total of 45 heavily pretreated metastatic colorectal cancer patients were prospectively evaluated for circulating levels of VEGF during the treatment with cetuximab plus weekly irinotecan. VEGF circulating levels 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 VEGF median levels were significantly decreased just 1 day after the first anticancer infusion (p = 0.016) and reached the highest statistical significance 92 days after the first infusion (p < 0.0001). A total of 22 patients showed a reduction in median VEGF circulating levels of at least 50% 92 days after the first infusion with respect to the basal time point. For patients with at least a 50% reduction in VEGF levels, the response rate was 45.5% compared with 8.7% in the nonreduced VEGF group (p = 0.014). The median time to progression was 6 months in the reduced VEGF group versus 3.9 months in the other patients (p < 0.0001). In addition, overall survival was longer in patients with VEGF reduction (11.0 months) than in patients without (9.6 months; p = 0.01).


CONCLUSIONS
These data represent the first evidence that suggests a role of VEGF reduction in the prediction of efficacy of treatment with cetuximab plus weekly irinotecan in heavily pretreated advanced colorectal cancer patients.
Vincenzi
Bruno
B
University Campus Bio-Medico, Medical Oncology, Via Emilio Longoni, 69, 00155, Rome, Italy. b.vincenzi@unicampus.it
Santini
Daniele
D
Russo
Antonio
A
Gavasci
Michele
M
Battistoni
Fabrizio
F
Dicuonzo
Giordano
G
Rocci
Laura
L
Rosaria
Valerio Maria
VM
Gebbia
Nicola
N
Tonini
Giuseppe
G
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000097:blood* / Q000188:drug therapy* / Q000401:mortality; D018450:Disease Progression; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D015996:Survival Rate / Q000639:trends; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000097:blood*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D042461:Vascular Endothelial Growth Factor A; D000077146:Irinotecan; D000068818:Cetuximab; D002166:Camptothecin