ATTACHE

A Trial in the Timing of Surgery and Adjuvant Chemotherapy for Hepatic Metastases from Colorectal Cancer.

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Trial Status

Completed

Cancer Type

Colorectal Cancer

Aim

A randomised phase III  multi‐centre  comparison  of chemotherapy given prior to and post surgical resection versus chemotherapy given post surgical resection. Eligible patients will be randomised to receive 6 months of treatment post‐operatively or 3 months of treatment pre‐operatively and 3 months post‐operatively. Site investigators must nominate which chemotherapy schedule they will use prior to randomisation.

Summary

The  liver  is  the  most  common  site  of  colorectal  cancer metastases with 25% of patients presenting with liver metastases at diagnosis and an additional 25 – 40% developing liver metastases on disease recurrence. These patients have a poor prognosis, despite improvements in survival over the last decade due to chemotherapy. Surgical resection of liver metastases is considered the only curative treatment option for patients with metastatic disease confined to the liver where the liver metastases are considered resectable. It has become an essential part of the management of metastatic colorectal cancer in such patients. However, following hepatectomy, recurrences are observed in up to up to two‐thirds of patients, half of them occurring in the liver.

In an attempt to improve the outcomes for this group of potentially curable patients, the use of adjuvant chemotherapy after liver resection has been increasingly studied. Subsequent to the use of post‐operative chemotherapy, the use of peri‐operative chemotherapy has been reported in a randomised controlled trial and in three longitudinal cohort studies.

To date, no randomised studies have directly compared the role of peri‐operative chemotherapy to adjuvant chemotherapy for resectable liver metastases. Benefit from post operative or adjuvant chemotherapy compared to peri‐operative treatment has been suggested in a recent retrospective study of 499 patients with resected colorectal liver metastases which showed an improved survival with post‐ operative rather than peri‐operative chemotherapy. Given this data and that of the small randomised trials showing an improvement for patients with adjuvant chemotherapy, it is critical that the role of post ‐ operative chemotherapy alone as a means of improving outcomes while reducing the negative effects of pre‐operative treatment is examined.

Trial Status

Completed

Cancer Type

Colorectal Cancer

Conference Presentation Reference

  1. Goldstein D, Fawcett J, Bridgewater J, Choti M, Wilson K, Gebski V, Aiken C, Eminton Z, Falk S, Stanton L, Primrose J. Safety and toxicity of peri‐operative and post‐operative adjuvant therapy for hepatic metastases from colorectal cancer: results from AGITG ATTACHE, CRUK EPOC‐B and NSABP C‐11. European Cancer Congress 2015; 25-29 Sep 2015; Vienna.
  2. Fawcett J, Sjoquist K, Padbury R, Christophi C, Tebbutt N, Pilgrim C, Gebski V, Aiken C, Wong N, Goldstein D. 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. American Society of Clinical Oncology Annual Meeting; 1–5 Jun 2012; Chicago.
  3. Sjoquist K, Goldstein D, Fawcett J, Padbury R, Christophi C, Tebbutt N, Gebski V, Wong N, Aiken C. ATTACHE: a trial in the timing of surgery and adjuvant chemotherapy for hepatic metastases from colorectal cancer. Clinical Oncological Society of Australia (COSA) Annual Scientific Meeting; 9–11 Nov 2010; Melbourne. Asia-Pacific Journal of Clinical Oncology 2010; 6(suppl 3): 184. Abstract 295.

Aim

A randomised phase III  multi‐centre  comparison  of chemotherapy given prior to and post surgical resection versus chemotherapy given post surgical resection. Eligible patients will be randomised to receive 6 months of treatment post‐operatively or 3 months of treatment pre‐operatively and 3 months post‐operatively. Site investigators must nominate which chemotherapy schedule they will use prior to randomisation.

Summary

The  liver  is  the  most  common  site  of  colorectal  cancer metastases with 25% of patients presenting with liver metastases at diagnosis and an additional 25 – 40% developing liver metastases on disease recurrence. These patients have a poor prognosis, despite improvements in survival over the last decade due to chemotherapy. Surgical resection of liver metastases is considered the only curative treatment option for patients with metastatic disease confined to the liver where the liver metastases are considered resectable. It has become an essential part of the management of metastatic colorectal cancer in such patients. However, following hepatectomy, recurrences are observed in up to up to two‐thirds of patients, half of them occurring in the liver.

In an attempt to improve the outcomes for this group of potentially curable patients, the use of adjuvant chemotherapy after liver resection has been increasingly studied. Subsequent to the use of post‐operative chemotherapy, the use of peri‐operative chemotherapy has been reported in a randomised controlled trial and in three longitudinal cohort studies.

To date, no randomised studies have directly compared the role of peri‐operative chemotherapy to adjuvant chemotherapy for resectable liver metastases. Benefit from post operative or adjuvant chemotherapy compared to peri‐operative treatment has been suggested in a recent retrospective study of 499 patients with resected colorectal liver metastases which showed an improved survival with post‐ operative rather than peri‐operative chemotherapy. Given this data and that of the small randomised trials showing an improvement for patients with adjuvant chemotherapy, it is critical that the role of post ‐ operative chemotherapy alone as a means of improving outcomes while reducing the negative effects of pre‐operative treatment is examined.

Principal Investigator

Professor Jonathan Fawcett & Professor David Goldstein