TY - JOUR
T1 - A randomized phase II trial of three intensified chemotherapy regimens in first-line treatment of colorectal cancer patients with initially unresectable or not optimally resectable liver metastases. the METHEP trial
AU - Ychou, Marc
AU - Rivoire, Michel
AU - Thezenas, Simon
AU - Quenet, Francois
AU - Delpero, Jean Robert
AU - Rebischung, Christine
AU - Letoublon, Christian
AU - Guimbaud, Rosine
AU - Francois, Eric
AU - Ducreux, Michel
AU - Desseigne, Francoise
AU - Fabre, Jean Michel
AU - Assenat, Eric
N1 - Funding Information:
CONFLICT OF INTEREST Marc Ychou has received Grant research funding from Pfizer and has consultant/advisory relationships with Pfizer. He has no leadership position, stock ownership, expert testimony or other remuneration disclosures. Michel Rivoire, Simon Thezenas, Franc¸ois Quenet, Jean-Robert Delpero, Christine Rebischung, Christian Letoublon, Rosine Guimbaud, Eric Franc¸ois, Michel Ducreux, Franc¸oise Desseigne, Jean-Michel Fabre, and Eric Assenat have no disclosures.
Funding Information:
ACKNOWLEDGMENT The authors acknowledge Mrs. Vanessa Guillaumon for editorial assistance. Funding was provided by Grants from CHUGAI, PFIZER, and SANOFI-AVENTIS.
PY - 2013/8/19
Y1 - 2013/8/19
N2 - Purpose. This study was designed to evaluate neoadjuvant intensified chemotherapy in potentially resectable or unresectable liver metastases (LM) from colorectal cancer (CRC). Methods. Criteria for potentially resectable LM were complex hepatectomy and/or risky procedure, close contact with major vascular structures, and for unresectable LM, a future liver remnant predicted to be less than 25-30 % of total liver volume. Between October 2004 and August 2007, 125 patients were randomized to either standard (FOLFIRI/FOLFOX4) or intensified chemotherapy (FOLFIRI- HD/FOLFOX7/FOLFIRINOX). Primary endpoint was objective response rate (ORR) after 4 cycles of chemotherapy. Secondary endpoints included safety, R0 surgical resection, best ORR, progression-free survival (PFS), and overall survival (OS). Results. A total of 122 patients were treated; 45 % of patients had less than 30 % of remaining liver tissue, 20 % had major vascular contact, and 35 % were potentially resectable. Grade 3/4 toxicities were neutropenia (24, 19, 10, 23 %) diarrhoea (0, 6, 3, 23 %), mucositis (0, 3, 0, 7 %), vomiting (7, 9, 0, 3 %), and neurotoxicity (0, 0, 10, 3 %) in arms (FOLFIRI ? FOLFOX4)/FOLFIRI-HD/ FOLFOX7/FOLFIRINOX, respectively. ORR was 33, 47, 43, and 57 % after the first 4 cycles in arms (FOLFIRI ? FOLFOX4)/FOLFIRI-HD/FOLFOX7/FOLFIRINOX, respectively. FOLFIRINOX offered the best conversion rate to resectability (67 %). Disease-free status after chemotherapy and surgery (R0, R1, Rx) was achieved in 54 of 64 operated patients. Median PFS was 9.2 months in control arms versus 11.9 months in experimental arms (hazards ratio [HR] = 0.76, p = 0.115), and the median OS was 17.7 versus 33.4 months (HR = 0.73, p = 0.297), respectively. Conclusions. FOLFIRINOX showed promising activity in CRC patients with LM compared with standard or intensified bi-chemotherapy regimens.
AB - Purpose. This study was designed to evaluate neoadjuvant intensified chemotherapy in potentially resectable or unresectable liver metastases (LM) from colorectal cancer (CRC). Methods. Criteria for potentially resectable LM were complex hepatectomy and/or risky procedure, close contact with major vascular structures, and for unresectable LM, a future liver remnant predicted to be less than 25-30 % of total liver volume. Between October 2004 and August 2007, 125 patients were randomized to either standard (FOLFIRI/FOLFOX4) or intensified chemotherapy (FOLFIRI- HD/FOLFOX7/FOLFIRINOX). Primary endpoint was objective response rate (ORR) after 4 cycles of chemotherapy. Secondary endpoints included safety, R0 surgical resection, best ORR, progression-free survival (PFS), and overall survival (OS). Results. A total of 122 patients were treated; 45 % of patients had less than 30 % of remaining liver tissue, 20 % had major vascular contact, and 35 % were potentially resectable. Grade 3/4 toxicities were neutropenia (24, 19, 10, 23 %) diarrhoea (0, 6, 3, 23 %), mucositis (0, 3, 0, 7 %), vomiting (7, 9, 0, 3 %), and neurotoxicity (0, 0, 10, 3 %) in arms (FOLFIRI ? FOLFOX4)/FOLFIRI-HD/ FOLFOX7/FOLFIRINOX, respectively. ORR was 33, 47, 43, and 57 % after the first 4 cycles in arms (FOLFIRI ? FOLFOX4)/FOLFIRI-HD/FOLFOX7/FOLFIRINOX, respectively. FOLFIRINOX offered the best conversion rate to resectability (67 %). Disease-free status after chemotherapy and surgery (R0, R1, Rx) was achieved in 54 of 64 operated patients. Median PFS was 9.2 months in control arms versus 11.9 months in experimental arms (hazards ratio [HR] = 0.76, p = 0.115), and the median OS was 17.7 versus 33.4 months (HR = 0.73, p = 0.297), respectively. Conclusions. FOLFIRINOX showed promising activity in CRC patients with LM compared with standard or intensified bi-chemotherapy regimens.
UR - http://www.scopus.com/inward/record.url?scp=84892370574&partnerID=8YFLogxK
U2 - 10.1245/s10434-013-3217-x
DO - 10.1245/s10434-013-3217-x
M3 - Article
C2 - 23955585
AN - SCOPUS:84892370574
SN - 1068-9265
VL - 20
SP - 4289
EP - 4297
JO - Annals of Surgical Oncology
JF - Annals of Surgical Oncology
IS - 13
ER -