Bevacizumab plus FOLFIRI-3 in chemotherapy-refractory patients with metastatic colorectal cancer in the era of biotherapies.
BACKGROUND
The optimal chemotherapeutic regimen suitable for metastatic colorectal cancer (mCRC) patients previously treated with 5-fluorouracil (5FU), oxaliplatin, irinotecan and biotherapies remains an unresolved issue. The aim of this study was to evaluate the activity of bevacizumab combined with FOLFIRI-3 in mCRC after failure of prior chemotherapy including fluoropyrimidine, irinotecan and oxaliplatin.


METHODS
Patients were treated with bevacizumab in combination with FOLFIRI-3 every 14 days. The association between treatment efficacy and visceral fat area as measured by CT scan or Carcinoembryonic Antigen (CEA) change after 2 months was also studied.


RESULTS
Forty-nine consecutive patients were treated. Four hundred and twenty four cycles of chemotherapy were delivered. Median follow-up was 11 months. Eleven patients (22.4%) had an objective partial response and 26 (53.1%) were stabilized. Median progression-free survival (PFS) and overall survival (OS) were 7 and 13 months respectively. Four grade 4 adverse events occurred (1 digestive perforation, 1 rectal ulcer, 1 pulmonary embolism, and 1 febrile aplasia) but no toxic death was observed. Grade 3 adverse events occurred in 18 patients (38%) including asthenia in 15 patients (30%), nausea and vomiting in 4 patients (8%), diarrhea in 11 patients (22%), anemia in 4 patients (8%), neutropenia in 10 patients (20%) and thrombopenia in 4 patients (8%). Visceral Fat area was significantly lower in responder patients. CEA change at 2 months predicted improved overall survival.


CONCLUSIONS
This study suggests that bevacizumab combined with FOLFIRI3 may be active in mCRC patients after failure of all classical lines of chemotherapy.
Department of Medical Oncology, Georges Francois Leclerc Cancer Center, 1 rue du professeur Marion, Dijon 21000, France. fghiringhelli@cgfl.fr
François
F
Ghiringhelli
Julie
J
Vincent
Boris
B
Guiu
Bruno
B
Chauffert
Sylvain
S
Ladoire
D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D002272:Carcinoembryonic Antigen / Q000097:blood; D015179:Colorectal Neoplasms / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005602:France; D006801:Humans; D007262:Infusions, Intravenous; D050152:Intra-Abdominal Fat / Q000000981:diagnostic imaging; D000077146:Irinotecan; D053208:Kaplan-Meier Estimate; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D017211:Treatment Failure
D061067:Antibodies, Monoclonal, Humanized; D002272:Carcinoembryonic Antigen; D000068258:Bevacizumab; D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin