Neoadjuvant chemotherapy for unresectable liver metastases
Patients with hepatic metastases that are deemed unresectable will occasionally become candidates for resection if they have a good response to chemotherapy. These patients have 5-year survival rates similar to patients who initially had resectable disease. There is no consensus on the best regimen to use to convert unresectable isolated liver metastases to resectable liver metastases.
Radiofrequency ablation has emerged as a safe technique (2% major morbidity and <1% mortality rate) that may provide for long-term tumor control.[18,19,20,21,22,23,24] Radiofrequency ablation and cryosurgical ablation [25,26,27,28] remain options for patients with tumors that cannot be resected and for patients who are not candidates for liver resection.
Other local ablative techniques that have been used to manage liver metastases include embolization and interstitial radiation therapy.[29,30] Patients with limited pulmonary metastases, and patients with both pulmonary and hepatic metastases, may also be considered for surgical resection, with 5-year survival possible in highly-selected patients.[12,31,32]
Adjuvant or neoadjuvant chemotherapy for resectable liver metastases
The role of adjuvant chemotherapy after potentially curative resection of liver metastases is uncertain.
Evidence (adjuvant or neoadjuvant chemotherapy for resectable liver metastases):
In the era before the use of FOLFOX (folinic acid [LV], 5-fluorouracil [5-FU], and oxaliplatin) and FOLFIRI (5-FU and irinotecan), two trials attempted to randomly assign patients after resection of liver metastases to 5-FU/LV or observation, but both studies were closed early because of poor accrual.
- The FFCD-9902 [NCT00304135] trial randomly assigned 173 patients (200 patients were planned) to postoperative 5-FU/LV, which is the Mayo Clinic regimen, or observation.
- 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 for recurrence or death, 0.66; 95% confidence interval [CI], 0.46-0.96; P = .028). The 5-year overall survival (OS) was not significantly different between the groups (chemotherapy group, 51.1% vs. the control group, 41.1%; odds ratio for death, 0.73; 95% CI, 0.48-1.10; P = .13).
- The European Organization 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.
- 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). 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).