ATTACHE: A phase III, multicenter, randomized comparison of chemotherapy given prior to and post surgical resection versus chemotherapy given post surgical resection for hepatic metastases from colorectal cancer.

TPS3643 Background: No randomized studies have directly compared the role of peri-operative to adjuvant chemotherapy for resectable liver metastases. Benefit from post operative compared to peri-operative treatment has been suggested in a recent retrospective study of 499 patients with resected colorectal liver metastases which showed improved survival with entirely post-operative chemotherapy. Given this data and that of the small randomised trials demonstrating improved surgical outcomes with adjuvant chemotherapy, the role of entirely post-operative chemotherapy as a means of improving outcomes while reducing the negative effects of pre-operative treatment needs to be examined. Methods: 200 patients randomized 1:1 to 6 months of treatment post-operatively or 3 months of treatment pre-operatively and 3 months post-operatively. Site investigators will nominate chemotherapy schedule (mFOLFOX6, XELOX or FOLFIRI when adjuvant oxaliplatin received previously) prior to randomisation. Primary endpoint: proportion of patients in each arm with surgical complications within 30 days. Secondary endpoints: proportion of patients completing planned chemotherapy, post operative mortality rate (in each group), tolerability and safety of treatment, response rate by RECIST V1.1 and CEA, time to progression, time to treatment failure, overall survival, QoL (EORTC QLQ-C30 and QLQ-LMC21). A planned prospective meta-analysis with MRC (UK) and NSABP C-11 trials will have sufficient power to examine the effect of schedule (peri- or post-operative) on progression free survival (PFS). Eligibility: Patients with histologically proven colorectal cancer with radiologically confirmed, resectable liver metastases without evidence of extra-hepatic disease are eligible. Patients with synchronous metastases who have undergone resection of the primary tumour are eligible but patients requiring combined resection of primary cancer and liver metastatic disease are excluded. Patients with involved hilar nodes or wound implant metastases will not be eligible. Trial Status: Study opened to accrual August 2011.

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The role of peri-operative treatment in resectable liver metastases of colorectal cancer

Therapeutic Advances in Medical Oncology ◽

10.1177/1758834010375095 ◽

2010 ◽

Vol 2 (6) ◽

pp. 389-398 ◽

Cited By ~ 2

Author(s):

Alexander Stein ◽

Joern Rüssel ◽

Stefan Peinert ◽

Dirk Arnold

Keyword(s):

Colorectal Cancer ◽

Liver Metastases ◽

Operative Treatment

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Oral adjuvant chemotherapy using uracil-tegafur (UFT) with leucovorin (LV) after resection of colorectal cancer liver metastases: Long-term survival results of the phase III UFT/LV study.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.4_suppl.672 ◽

2017 ◽

Vol 35 (4_suppl) ◽

pp. 672-672 ◽

Cited By ~ 3

Author(s):

Kiyoshi Hasegawa ◽

Akio Saiura ◽

Tadatoshi Takayama ◽

Shinichi Miyagawa ◽

Junji Yamamoto ◽

...

Keyword(s):

Colorectal Cancer ◽

Adjuvant Chemotherapy ◽

Liver Metastases ◽

Curative Resection ◽

Phase Iii ◽

Control Group ◽

Colorectal Cancer Liver Metastases ◽

The Impact ◽

Better Than

672 Background: Surgical resection has been accepted as the standard therapy for colorectal cancer liver metastases (CRLM), however, high recurrence incidence even after curative resection remains a severe problem. The 1st analysis of the UFT/LV trial showed that oral UFT/LV for 6 months significantly prolonged relapse-free survival (RFS) after resection for CRLM (Kobayashi A et al. ASCO 2014, Hasegawa K et al. PlosOne 2016 E-pub). To further evaluate the impact of the UFT/LV therapy on overall survival (OS), we performed the 2nd analysis under longer follow-up period, as have been scheduled by the protocol. Methods: Patients undergoing curative resection of CRLM were randomly assigned to either UFT/LV or surgery alone (control) group. In the UFT/LV group, 5 cycles of adjuvant UFT/LV (UFT 300mg/m2 and LV 75 mg/day for 28 days followed by 7 days rest in one cycle) were administered. Results: Between 2004 and 2010, a total of 180 patients were enrolled to this trial, among whom 3 patients were ineligible for analysis. Median follow-up of the 2nd analysis was 6 years. The 5y-OS rate in the UFT/LV group was 65.3%, which was slightly better than the control group (62.2%) without statistical significance. The hazard ratio for death in the UFT/LV relative to the control was 0.86 (95% confidence interval: 0.54-1.38, P = 0.54). The OS curves of the 2 groups were identical within 4 years after resection, however, the OS curve of the UFT/LV group seemed to go higher than the control group. The 5y-RFS rate in the UFT/LV group was 36.2%, which was significantly better than that in the control group (32.3%), as have been shown by the 1st analysis. Conclusions: The results of the 2nd analysis suggested that oral UFT/LV adjuvant chemotherapy might be also useful to prolong OS, as have been confirmed for RFS. This regimen can be recommended as an alternative choice after hepatic resection for CRLM. Clinical trial information: C000000013.

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Biologic Therapies in Colorectal Cancer: Indications and Contraindications

American Society of Clinical Oncology Educational Book ◽

10.14694/edbook_am.2015.35.e197 ◽

2015 ◽

pp. e197-e206 ◽

Cited By ~ 4

Author(s):

Marwan Fakih

Keyword(s):

Colorectal Cancer ◽

Neoadjuvant Chemotherapy ◽

Liver Metastases ◽

Metastatic Disease ◽

Growth Factor Receptor ◽

Phase Iii ◽

Current Evidence ◽

Borderline Resectable ◽

Phase Iii Clinical Trials

The role of antiangiogenic and anti-epidermal growth factor receptor (EGFR) agents has been investigated extensively in colorectal cancer in the palliative, adjuvant, and neoadjuvant settings. Although the role of biologic agents has become well-defined in the first, second, and subsequent lines of treatment of metastatic colorectal cancer (mCRC), considerable debate continues around the optimal sequencing and around optimal patient selection. The benefits from integrating bevacizumab or cetuximab in the adjuvant setting have been investigated in several randomized phase III clinical trials in stage II/III disease, all with disappointing results. Neoadjuvant approaches incorporating biologic therapy in patients with liver metastatic disease have led to mixed results. Although the current evidence does suggest increased down-staging and increased resectability with the addition of cetuximab in patients with initially unresectable or borderline resectable liver metastases, a positive effect of anti-EGFR therapy on the overall survival (OS) in this setting is not conclusive. Patients with resectable liver metastases derive no benefit and may experience potential harm from the addition of cetuximab to neoadjuvant chemotherapy. Similarly, there is neither rationale nor adequate data to support the addition of bevacizumab to neoadjuvant chemotherapy in patients with resectable liver metastases. In this review, we examine the role of antiangiogenesis and anti-EGFR therapies across the spectrum of adjuvant, neoadjuvant, and metastatic disease.

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Role of Adjuvant Therapy After Resection of Colorectal Cancer Liver Metastases

Journal of Clinical Oncology ◽

10.1200/jco.2009.26.9340 ◽

2010 ◽

Vol 28 (13) ◽

pp. 2300-2309 ◽

Cited By ~ 48

Author(s):

Derek G. Power ◽

Nancy E. Kemeny

Keyword(s):

Colorectal Cancer ◽

Liver Resection ◽

High Risk ◽

Adjuvant Chemotherapy ◽

Liver Metastases ◽

Metastatic Colorectal Cancer ◽

Adjuvant Treatment ◽

Systemic Chemotherapy ◽

Perioperative Therapy

Liver resection is the goal of treatment strategies for liver-confined metastatic colorectal cancer. However, after resection the majority of patients will experience recurrence. Chemotherapy seems to improve outcomes compared with surgery alone. We reviewed the data of the role of adjuvant chemotherapy after resection of liver- confined metastatic colorectal cancer. Optimal regimens and sequencing of chemotherapies when liver resection is an option are unclear. Some suggest that resectable liver metastases, in the absence of high-risk features, should begin with surgery and consideration given to adjuvant chemotherapy after surgery. If high-risk features are present, most physicians prefer a short course of systemic preoperative chemotherapy. Perioperative therapy and regional therapy with hepatic arterial infusion (HAI) both increase disease-free survival (DFS) when compared with surgery alone. In unresectable disease, consideration should be given to systemic chemotherapy with or without a biologic agent or HAI with systemic therapy. If the disease becomes resectable, adjuvant treatment should follow surgery. Adjuvant chemotherapy is usually FOLFOX, but HAI combined with systemic chemotherapy is also an option. The role of adjuvant treatment post-liver resection should not be viewed in isolation but rather in the context of prior treatment, surgical preference, and individual patient characteristics. Perioperative therapy and regional therapy have both shown an increase in DFS. Conducting randomized trials examining the role of adjuvant chemotherapy has been difficult because of rapidly changing chemotherapies.

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