Surgical resection of liver metastases of colorectal cancer greatly improves the

Surgical resection of liver metastases of colorectal cancer greatly improves the clinical outcome of patients with advanced disease. survival. = 0.028) suggesting a positive effect of chemotherapy after surgery. There was a trend toward increased 5-year overall survival (OS) in patients who received chemotherapy without statistical significance (51.1% 41.9% = 0.13). The study may have been statistically underpowered to detect a true difference in OS as a result of early termination of accrual GSK461364 due to low accrual rates. An another trial [European Organisation for Research and Treatment of Cancer (EORTC)/National Cancer Institute of Canada Clinical Trials Group (NCIC CTG)/Gruppo Interdisciplinare Valutazione Interventi in Oncologia (GIVIO) trial] with a similar design also closed prematurely due to slow accrual but showed a trend towards improved progression-free survival (PFS) and OS in the chemotherapy group. Multivariate analysis identified adjuvant chemotherapy as a significant GSK461364 independent prognostic factor GSK461364 even though between-group comparison was insignificant[11]. Some large United States and European retrospective analyses further suggested an urgent need for patients with recurrent disease to receive adjuvant chemotherapy and showed a better survival in resected CLM patients who received adjuvant therapy[12 13 The choice of regimen is the key to the success of chemotherapy after tumor resection. The 5-FU/LV regimen is less commonly used nowadays but the efficacy of combining 5-FU with oxaliplatin or irinotecan as postoperative chemotherapy for patients with resectable GSK461364 CLM remains to be elucidated. A randomized phase III study comparing adjuvant 5-FU/LV with FOLFIRI in patients following complete resection of CLM reported a median DFS of 24.7 mo and 21.6 mo for FOLFIRI and 5-FU/LV respectively with no significant differences noted for DFS and OS however a trend in favor of improved DFS in patients treated with FOLFIRI could not be excluded[14]. At present evidence to support significant additional benefit using combination therapies for resectable CLM has not been established. Thus the use of postoperative therapy is individualized based on local practice as well-established data from clinical trials are not yet available. The expert panel of the European Colorectal Metastases Treatment Group recommends that systemic chemotherapy following liver resection should be considered as an option for patients with resected CLM particularly for those patients who did not receive preoperative chemotherapy[8]. PREOPERATIVE CHEMOTHERAPY FOR RESECTABLE CLM Rising enthusiasm for the role of perioperative chemotherapy in cases of operable carcinoma originating from the digestive system has been noted including those with CLM. Convincing benefits of preoperative chemotherapy on long-term survival in patients with CLM is still not well-established but it is gradually being accepted as the rationale to improve PFS and reduce recurrence rates[15]. A ten-year study on survival and recurrence after neoadjuvant chemotherapy followed by resection of liver metastases Rabbit Polyclonal to RFA2 (phospho-Thr21). showed that the 1- 3 and 5-year OS reached 90% 59.2% and 46.1% respectively and DFS at 1 3 and 5 years was 68.1% 34.8% and 27.9% respectively. In addition preoperative chemotherapy followed by liver metastases resection is associated with improved survival low cancer involvement in resection margins and re-resection rates[16]. In 2008 Nordlinger et al[17] published the final results of the EORTC 40983 study which compared perioperative chemotherapy with oxaliplatin fluorouracil and folinic acid (FOLFOX4) regimen to surgery alone in patients with resectable CLM. Patients were randomly assigned to six cycles of neoadjuvant FOLFOX4 before and after surgery (= 182) or to surgery alone (= 182). The 3-year PFS was improved from 28.1% for the surgery-alone group to 36.2% for the perioperative FOLFOX4 group an increase of 8.1% [hazard ratio (HR) = 0.77; = 0.041] for all eligible patients and 9.2% (HR = 0.73; = 0.025) for all resected patients. Additional reports on the application of neoadjuvant chemotherapy came from a few prospective single-center clinical trials[18 19 In one trial 50 patients with resectable liver metastases received neoadjuvant capecitabine plus oxaliplatin (XELOX) or FOLFOX4.