Adjuvant or neoadjuvant chemotherapy for resectable liver metastases

The FFCD-9902 trial (NCT00304135) randomly assigned 173 patients (200 patients were planned) to postoperative 5-FU/LV, which is the Mayo Clinic regimen, or observation.[35]

The FFCD-9902 trial (NCT00304135) randomly assigned 173 patients (200 patients were planned) to postoperative 5-FU/LV, which is the Mayo Clinic regimen, or observation.[35]

The 5-year disease-free survival (DFS) rate was 33.5% for patients in the chemotherapy group and 26.7% for patients in the control group (Cox multivariate analysis: odds ratio (OR) for recurrence or death, 0.66; 95% confidence interval [CI], 0.46–0.96; P = .028). The 5-year OS rate was not significantly different between the groups (chemotherapy group, 51.1% vs. the control group, 41.1%; ORdeath, 0.73; 95% CI, 0.48–1.10; P = .13).

The European Organisation for Research and Treatment of Cancer/National Cancer Institute of Canada/Gruppo Interdisciplinare Valutazione Interventi in Oncologia (EORTC/NCIC/GIVIO) International trial attempted a similar random assignment of patients after surgical resection of liver metastases. The study closed because of poor accrual, and a combined analysis of the study and the FFCD-9902 study was done instead. In the combined analysis, 278 patients (138 of whom received chemotherapy; 14 of whom received surgery alone) were included.[36]

The European Organisation for Research and Treatment of Cancer/National Cancer Institute of Canada/Gruppo Interdisciplinare Valutazione Interventi in Oncologia (EORTC/NCIC/GIVIO) International trial attempted a similar random assignment of patients after surgical resection of liver metastases. The study closed because of poor accrual, and a combined analysis of the study and the FFCD-9902 study was done instead. In the combined analysis, 278 patients (138 of whom received chemotherapy; 14 of whom received surgery alone) were included.[36]

The median progression-free survival (PFS) was 27.9 months in the chemotherapy arm and 18.8 months in the surgery alone arm (hazard ratio [HR], 1.32; 95% CI, 1.00–1.76; P = .058).

The European Organisation for Research and Treatment of Cancer/National Cancer Institute of Canada/Gruppo Interdisciplinare Valutazione Interventi in Oncologia (EORTC/NCIC/GIVIO) International trial attempted a similar random assignment of patients after surgical resection of liver metastases. The study closed because of poor accrual, and a combined analysis of the study and the FFCD-9902 study was done instead. In the combined analysis, 278 patients (138 of whom received chemotherapy; 14 of whom received surgery alone) were included.[36]

The median OS was 62.2 months in the chemotherapy arm compared with 47.3 months in the surgery-alone arm (HR, 1.32; 95% CI, 0.95–1.82; P = .095).

A phase III study randomly assigned 306 patients to 5-FU/LV or FOLFIRI after a resection of liver metastases.[37]

A phase III study randomly assigned 306 patients to 5-FU/LV or FOLFIRI after a resection of liver metastases.[37]

There was no difference in DFS (21.6 months for 5-FU/LV vs. 24.7 months for FOLFIRI; HR, 0.89; log-rank P = .44) or OS (HR, 1.09; 95% CI, 0.72–1.64).

The EORTC-40983 trial (NCT00006479) randomly assigned 364 patients with up to four resectable liver metastases to perioperative FOLFOX (six cycles presurgery and six cycles postsurgery) or surgery alone.[38]

The EORTC-40983 trial (NCT00006479) randomly assigned 364 patients with up to four resectable liver metastases to perioperative FOLFOX (six cycles presurgery and six cycles postsurgery) or surgery alone.[38]

The PFS rate was 28.1% (95.66% CI, 21.3%–35.5%) for the surgery-alone group and 35.4% (28.1%–42.7%; HR, 0.79; 0.62–1.02; P = .058) for the perioperative chemotherapy group. There was no difference in OS. Subsequent post hoc analysis demonstrated that the difference in PFS in truly eligible patients rose 8.1% (from 28.1% [21.2%–36.6%] to 36.2% [28.7%–43.8%]; HR, 0.77 [0.60–1.00]; P = .041). In patients who underwent resection of liver metastases, the difference in PFS rose 9.2% (from 33.2% [25.3%–41.2%] to 42.4% [34.0%–50.5%]; HR, 0.73 [0.55–0.97]; P = .025).

The EORTC-40983 trial (NCT00006479) randomly assigned 364 patients with up to four resectable liver metastases to perioperative FOLFOX (six cycles presurgery and six cycles postsurgery) or surgery alone.[38]

Reversible postoperative complications occurred more often after chemotherapy than after surgery (40 [25%] of the 159 complications vs. 27 [16%] of the 170 complications; P = .04). After surgery, there were two deaths in the surgery-alone group and one in the perioperative chemotherapy group.