Achievements (2008 - 2009)
1. Colorectal cancer
In 2007, active studies in colorectal cancer included the large adjuvant study PETACC-8 (40052) and two studies in advanced disease, the BOS (40051) and CLOCC (40004) trials. A number of previous studies matured and were presented including primary results for the PETACC-1 (40962) , PETACC-3 (40993), EPOC (40983) and EORTC 40015.
A new study of perioperative chemoradiotherapy in locally advanced rectal cancer, PETACC-6 (40054-22026) was developed and will open in 2008 with an accrual goal of almost 1100 patients. In addition to the strong translational research (TR) components found in all active protocols, past projects such as PETACC-2 (40963) and PETACC-3 are proving to be a rich source of TR material. During the year, investigators developed a number of future studies as successors to the current ones, assuring a full pipeline for the foreseeable future.
In terms of public policy and outreach, the GI group participated as an expert group in the European Conference on Colon Cancer Prevent, sponsored by the Felix Burda Foundation in May 2007, and is a signatory to the Brussels Declaration of “Europe Against Colon Cancer”.
Adjuvant studies: The largest (more than 2000 patients) active trial in the group is an intergroup collaboration within the PETACC framework, PETACC-8, which is coordinated by the FFCD. This study compares adjuvant treatment of completely resected colon cancer with FOLFOX4 versus FOLFOX4 plus cetuximab.
Final results of PETACC-1 were presented to the group and submitted as an abstract; full publication will follow in 2008. This trial, which was a comparison of raltitrexed versus leucovorin-modulated 5-FU in resected Dukes C colorectal cancer, enrolled 1921 patients at the time of its early closure in 1999. It was a result of collaboration with national groups from Canada, Egypt, France, Germany, Italy, Portugal, Spain, The Netherlands and the UK.
Analysis of the final results of the PETACC-3 trial was completed in 2007, and publication will follow in 2008. In this trial, 3005 patients with stage II and III colon cancer were randomised between 5- FU/FA +/- irinotecan.
Advanced disease: The BOS (Biologicals-Oxaliplatin-Surgery) trial is a randomised phase II trial evaluating the feasibility and tolerance of the combination of FOLFOX with cetuximab and the combination of FOLFOX with cetuximab and bevacizumab as perioperative treatment in patients with resectable liver metastases from colorectal cancer. This trial activated in January 2007, with an accrual goal of 100 patients. The trial will continue through 2008, along with an ambitious TR programme.
The most important result to come out of the group in 2007 was the primary endpoint analysis for the EPOC (European Peri-Operative Colon) study, EORTC 40983. This 364-patient study examined the benefit of perioperative chemotherapy for patients with initially resectable liver-only metastases from colorectal cancer and arrived at the practice-altering conclusion that perioperative FOLFOX4 chemotherapy is safe and reduces the risk of PFS events by approximately 25% over surgery alone in these patients. At the time of this report, the corresponding paper is in press.
The final results for EORTC 40015 were published in 2007 (Annals of Oncology, doi:10.1093/annonc/ mdm544). The study aimed to demonstrate the noninferiority of capecitabine to 5-fluorouracil (5-FU)/folinic acid (FA), in relation to progression-free survival (PFS) after first-line treatment of metastatic colorectal cancer and the benefit of adding celecoxib (C) to irinotecan/fluoropyrimidine regimens compared with placebo (P). Because the study was terminated at an early point with a small sample, it was not able to provide specific conclusions in relation to the noninferiority of CAPIRI compared with FOLFIRI.
Safety results for the CLOCC trial, 40004, were presented and have been submitted as an abstract. This randomised phase III study of local treatment of liver metastases by radiofrequency combined with chemotherapy versus chemotherapy alone in patients with unresectable colorectal liver metastases was activated in 2002, and closed in 2007, after enrollment of 119 patients.
2. Pancreatic cancer
The first part of a randomised phase II/III study comparing gemcitabine followed by gemcitabine plus concomitant radiation (50.4 Gy) versus gemcitabine alone after curative pancreaticoduodenectomy for pancreatic head cancer was concluded and analysed in 2007, with progression to a phase III study expected in 2008. The phase II component of the study involved 97 patients.
3. Gastric cancer
The GI Group Gastric Cancer task force published its guidelines for treatment of gastric cancer in the December 2007 edition of the European Journal of Oncology. The task force also developed new gastric trial protocols which will launch in 2008. The results of the 40954 neoadjuvant gastric study were presented to the group, and are being prepared for publication in 2008.
4. Imaging in GI Cancers
The EORTC GI and Radiation Oncology groups held a joint meeting on the role of PET imaging in GI cancer in Heidelberg. In addition to imaging-specific proposals expected in 2008, imaging is expected to play a larger role across disease types, particularly the use of earlier imaging to direct therapy, and the use of functional imaging as a surrogate endpoint for drug effectiveness and disease response.
5. Anal Cancer
The 22011-40014 phase II-III trial of continuous fluorouracil plus mitomycin C versus mitomycin C plus Cisplatin as chemotherapy combination in combined radiochemotherapy for locally advanced anal cancer was closed in 2007, after recruitment of 88 patients. This trial was coordinated by the EORTC Radiation Oncology Group.