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Perioperative chemotherapy with FOLFOX4 and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC Intergroup trial 40983): a randomised controlled trial.

Nordlinger B, Sorbye H, Glimelius B, Poston GJ, Schlag PM, Rougier P, Bechstein WO, Primrose JN, Walpole ET, Finch-Jones M, Jaeck D, Mirza D, Parks RW, Collette L, Praet M, Bethe U, Van Cutsem E, Scheithauer W, Gruenberger T, EORTC Gastro-Intestinal Tract Cancer GroupCancer Research UKArbeitsgruppe Lebermetastasen und-tumoren in der Chirurgischen Arbeitsgemeinschaft Onkologie (ALM-CAO)Australasian Gastro-Intestinal Trials Group (AGITG)Fédération Francophone de Cancérologie Digestive (FFC - Lancet (2008)

Bottom Line: Primary analysis was by intention to treat.Analyses were repeated for all eligible (171 vs 171) and resected patients (151 vs 152).Perioperative chemotherapy with FOLFOX4 is compatible with major liver surgery and reduces the risk of events of progression-free survival in eligible and resected patients.

View Article: PubMed Central - PubMed

Affiliation: Centre Hospitalier Universitaire Ambroise Paré, Assistance Publique Hôpitaux de Paris, Departments of Surgery and Oncology, Boulogne-Billancourt, France. bernard.nordlinger@apr.aphp.fr

ABSTRACT

Background: Surgical resection alone is regarded as the standard of care for patients with liver metastases from colorectal cancer, but relapse is common. We assessed the combination of perioperative chemotherapy and surgery compared with surgery alone for patients with initially resectable liver metastases from colorectal cancer.

Methods: This parallel-group study reports the trial's final data for progression-free survival for a protocol unspecified interim time-point, while overall survival is still being monitored. 364 patients with histologically proven colorectal cancer and up to four liver metastases were randomly assigned to either six cycles of FOLFOX4 before and six cycles after surgery or to surgery alone (182 in perioperative chemotherapy group vs 182 in surgery group). Patients were centrally randomised by minimisation, adjusting for centre and risk score. The primary objective was to detect a hazard ratio (HR) of 0.71 or less for progression-free survival. Primary analysis was by intention to treat. Analyses were repeated for all eligible (171 vs 171) and resected patients (151 vs 152). This trial is registered with ClinicalTrials.gov, number NCT00006479.

Findings: In the perioperative chemotherapy group, 151 (83%) patients were resected after a median of six (range 1-6) preoperative cycles and 115 (63%) patients received a median six (1-8) postoperative cycles. 152 (84%) patients were resected in the surgery group. The absolute increase in rate of progression-free survival at 3 years was 7.3% (from 28.1% [95.66% CI 21.3-35.5] to 35.4% [28.1-42.7]; HR 0.79 [0.62-1.02]; p=0.058) in randomised patients; 8.1% (from 28.1% [21.2-36.6] to 36.2% [28.7-43.8]; HR 0.77 [0.60-1.00]; p=0.041) in eligible patients; and 9.2% (from 33.2% [25.3-41.2] to 42.4% [34.0-50.5]; HR 0.73 [0.55-0.97]; p=0.025) in patients undergoing resection. 139 patients died (64 in perioperative chemotherapy group vs 75 in surgery group). Reversible postoperative complications occurred more often after chemotherapy than after surgery (40/159 [25%] vs 27/170 [16%]; p=0.04). After surgery we recorded two deaths in the surgery alone group and one in the perioperative chemotherapy group.

Interpretation: Perioperative chemotherapy with FOLFOX4 is compatible with major liver surgery and reduces the risk of events of progression-free survival in eligible and resected patients.

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Related in: MedlinePlus

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fig1: Trial profile

Mentions: Figure 1 shows the trial profile. 364 patients were enrolled, 182 in each group. No log was kept of the number of patients who were screened for eligibility. Patient and tumour characteristics were much the same between the two groups at baseline (table 1). 11 patients in each group were ineligible. The reasons for ineligibility were more advanced disease than was allowed by the protocol (five in perioperative chemotherapy group and six in surgery group), primary liver cancer (one in both groups), no data (two in perioperative chemotherapy group and three in surgery group), second cancer (one in surgery group with colon cancer), late informed consent (one in perioperative chemotherapy group), high serum creatinine (one in perioperative chemotherapy group), and resection of primary less than 14 days of randomisation (one in perioperative chemotherapy group).


Perioperative chemotherapy with FOLFOX4 and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC Intergroup trial 40983): a randomised controlled trial.

Nordlinger B, Sorbye H, Glimelius B, Poston GJ, Schlag PM, Rougier P, Bechstein WO, Primrose JN, Walpole ET, Finch-Jones M, Jaeck D, Mirza D, Parks RW, Collette L, Praet M, Bethe U, Van Cutsem E, Scheithauer W, Gruenberger T, EORTC Gastro-Intestinal Tract Cancer GroupCancer Research UKArbeitsgruppe Lebermetastasen und-tumoren in der Chirurgischen Arbeitsgemeinschaft Onkologie (ALM-CAO)Australasian Gastro-Intestinal Trials Group (AGITG)Fédération Francophone de Cancérologie Digestive (FFC - Lancet (2008)

Trial profile
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2277487&req=5

fig1: Trial profile
Mentions: Figure 1 shows the trial profile. 364 patients were enrolled, 182 in each group. No log was kept of the number of patients who were screened for eligibility. Patient and tumour characteristics were much the same between the two groups at baseline (table 1). 11 patients in each group were ineligible. The reasons for ineligibility were more advanced disease than was allowed by the protocol (five in perioperative chemotherapy group and six in surgery group), primary liver cancer (one in both groups), no data (two in perioperative chemotherapy group and three in surgery group), second cancer (one in surgery group with colon cancer), late informed consent (one in perioperative chemotherapy group), high serum creatinine (one in perioperative chemotherapy group), and resection of primary less than 14 days of randomisation (one in perioperative chemotherapy group).

Bottom Line: Primary analysis was by intention to treat.Analyses were repeated for all eligible (171 vs 171) and resected patients (151 vs 152).Perioperative chemotherapy with FOLFOX4 is compatible with major liver surgery and reduces the risk of events of progression-free survival in eligible and resected patients.

View Article: PubMed Central - PubMed

Affiliation: Centre Hospitalier Universitaire Ambroise Paré, Assistance Publique Hôpitaux de Paris, Departments of Surgery and Oncology, Boulogne-Billancourt, France. bernard.nordlinger@apr.aphp.fr

ABSTRACT

Background: Surgical resection alone is regarded as the standard of care for patients with liver metastases from colorectal cancer, but relapse is common. We assessed the combination of perioperative chemotherapy and surgery compared with surgery alone for patients with initially resectable liver metastases from colorectal cancer.

Methods: This parallel-group study reports the trial's final data for progression-free survival for a protocol unspecified interim time-point, while overall survival is still being monitored. 364 patients with histologically proven colorectal cancer and up to four liver metastases were randomly assigned to either six cycles of FOLFOX4 before and six cycles after surgery or to surgery alone (182 in perioperative chemotherapy group vs 182 in surgery group). Patients were centrally randomised by minimisation, adjusting for centre and risk score. The primary objective was to detect a hazard ratio (HR) of 0.71 or less for progression-free survival. Primary analysis was by intention to treat. Analyses were repeated for all eligible (171 vs 171) and resected patients (151 vs 152). This trial is registered with ClinicalTrials.gov, number NCT00006479.

Findings: In the perioperative chemotherapy group, 151 (83%) patients were resected after a median of six (range 1-6) preoperative cycles and 115 (63%) patients received a median six (1-8) postoperative cycles. 152 (84%) patients were resected in the surgery group. The absolute increase in rate of progression-free survival at 3 years was 7.3% (from 28.1% [95.66% CI 21.3-35.5] to 35.4% [28.1-42.7]; HR 0.79 [0.62-1.02]; p=0.058) in randomised patients; 8.1% (from 28.1% [21.2-36.6] to 36.2% [28.7-43.8]; HR 0.77 [0.60-1.00]; p=0.041) in eligible patients; and 9.2% (from 33.2% [25.3-41.2] to 42.4% [34.0-50.5]; HR 0.73 [0.55-0.97]; p=0.025) in patients undergoing resection. 139 patients died (64 in perioperative chemotherapy group vs 75 in surgery group). Reversible postoperative complications occurred more often after chemotherapy than after surgery (40/159 [25%] vs 27/170 [16%]; p=0.04). After surgery we recorded two deaths in the surgery alone group and one in the perioperative chemotherapy group.

Interpretation: Perioperative chemotherapy with FOLFOX4 is compatible with major liver surgery and reduces the risk of events of progression-free survival in eligible and resected patients.

Show MeSH
Related in: MedlinePlus