Speaking at ECCO 13, leading expert in colorectal cancer epidemiology and prevention, Professor Peter Boyle from the International Agency for Research on Cancer (IARC), France, highlighted the important public health problem posed by the disease. In Europe in 2004, an estimated 197,200 men were diagnosed with colorectal cancer, representing 12.8% of new cancer cases. In the same year, colorectal cancer was diagnosed in approximately 179,200 women, representing 13% of new cancer cases and making it the second most common incident form of cancer in women.
Given that the majority of colorectal cancers occur in older people, and that the world's population as a whole is aging, this warrants further impetus to investigate prevention and treatment strategies among this subgroup of the population. Screening research, recommendations and implementation were highlighted by Professor Boyle as an obvious priority. In many European countries, only pilot programmes for colorectal screening are in place and mechanisms to ensure adequate coverage of the target groups need to be evaluated. However, some countries, such as Germany, have successfully implemented screening programmes. European Council Recommendations on Cancer Screening 2003 advise colorectal screening for men and women aged between 50 and 74. Professor Boyle concluded that Europe's goal should be to develop public health strategies to control the incidence of colorectal cancer in a rapidly aging European population.
With the situational perspective on colorectal cancer established, Nordic researchers presented their findings from a study evaluating different transatlantic treatment regimens for the metastatic form of the disease. Irinotecan combined with 5-fluorouracil (FU) and folinic acid (FA) is an established regimen for the treatment of metastatic colorectal cancer, however major uncertainties exist related to the mode of administration of FU. In the US, a weekly bolus schedule, the Saltz regimen, is used extensively, whereas in Europe, infused 5FU is preferred.
Irinotecan with the bolus FU/FA Nordic schedule (FLIRI) is a convenient treatment with efficacy and toxicity comparable to the 'infused' FOLFIRI regimen. In this study, irinotecan in combination with either the Nordic fortnightly 5FU/FA bolus schedule (FLIRI) or the fortnightly bolus/infused de Gramont schedule, known as FOLFIRI was administered to 557 previously untreated patients with metastatic colorectal cancer at 27 centres in the Nordic countries. The precise treatment schedule with FLIRI was irinotecan 180 mg/m2 on day 1, 5FU 500 mg/m2 bolus iv on day 1 and 2, plus FA 60 mg/m2 on days 1 and 2. In contrast, FOLFIRI consisted of irinotecan 180 mg/m2 on day 1, FA 200 mg/m2 on day 1 and 2, 5FU bolus 400 mg/m2 on day 1, 2 and infused 5FU 1 200 mg/m2 per 48 hour.
Results from the study were presented, with investigators highlighting that, in the entire patient population, toxicity did not differ between groups. The 60-day mortality was also similar between the two groups. Data on the primary endpoint of this study, which aims to assess any differences in progression-free survival between the two regimens, as well as response rates and time to progression will be available later in the year.
"Colorectal cancer imposes a significant burden of disease and all steps to improve and hone treatment regimens are an important undertaking," noted Dr Ake Berglund from Uppsala University, Sweden. "At ECCO we have seen evidence that irinotecan used with the bolus FLIRI schedule is a convenient treatment for metastatic colorectal cancer, with antitumour activity and toxicity comparable to the infused FOLFIRI regimen. Thus, patients can more easily be treated with a convenient bolus regimen without the need for a port and a pump."
About colorectal cancer
Colorectal cancer, also known as bowel cancer is the third most common cancer in men and the second most common in women.1,2There are approximately 377,000 cases of colorectal cancer across Europe each year and it is the cause of just under 204,000 deaths annually. 1
Colorectal cancer can occur anywhere in the colon or rectum. Cells lining the inside of the bowel are constantly renewing themselves and when this process goes wrong abnormal cells can arise. These cells form polyps which can eventually turn cancerous. Some of these polyps are non-cancerous but others can spread through the bowel layers and to other parts of the body, often the liver.
Symptoms experienced include: blood in faeces, changes in bowel habits, unexplained weight loss and a lump in the abdomen. Risk factors are associated with: age, (normally affects people over 50) history of chronic bowel inflammation, diet (high in red meat and fat and low in vegetables), lack of exercise, obesity, smoking and alcohol and family history.
There are three main treatments for colorectal cancer, surgery, radiotherapy and chemotherapy. If diagnosed early, surgery can be successful. Recently, innovations in chemotherapies such as irinotecan and experimental chemical agents are offering patients alternative treatments.
1 www.cancerresearchuk.org
2 Boyle, P. Cancer incidence and mortality in Europe, 2004. International Agency for Research on Cancer. 2004, p.483
For further information please contact:
Tonic Life Communications:
Stéphanie Makin: + 44 7769 673 973 or e-mail stephanie.makin@toniclc.com or
Kirsten Mason: + 44 7796 955 353 or e-mail kirsten.mason@toniclc.com
Press room:
Telephone: + 33 (0)1 40 68 27 45/ + 33 (0)1 40 68 27 46
Telefax: + 33 (01) 40 68 27 49/ + 33 (01) 40 68 27 52
For any enquiries after Thursday 3rd November 2005, please contact:
Stéphanie Makin: + 44 (0)20 7798 9905 or e-mail stephanie.makin@toniclc.com or
Kirsten Mason: + 44 (0)20 7798 9911 or e-mail kirsten.mason@toniclc.com
Abstract: 597
A randomised phase III multicenter trial comparing irinotecan in combination with either the Nordic bolus 5FU and folinic acid (5FU/FA) schedule (FLIRI) or the bolus/infused de Gramont schedule (FOLFIRI), in patients with metastatic colorectal cancer
B. Glimelius1, H. Sørbye2, L. Balteskard3, P. Byström4, P. Pfeiffer5, K. Tveit6, R. Heikkilä7, N. Keldsen8, H. Starkhammar9, Å. Berglund10
1Uppsala University Hospital, Dept of Oncol, Radiol and Clin Immunol, Uppsala, Sweden
2Haukeland University Hospital, Dept of Oncology, Bergen, Norway
3University Hospital, Dept of Oncology, Tromsö, Norway
4Karolinska Institutet, Dept of Oncology and Pathology, Stockholm, Sweden
5University Hospital, Dept of Oncology, Odense, Denmark
6Ullevål University Hospital, Dept of Oncology, Oslo, Norway
7Central Hospital in Rogaland, Dept of Oncology, Stavanger, Norway
8Central Hospital, Dept of Oncology, Herning, Denmark
9University Hospital, Dept of Oncology, Linköping, Sweden
10Uppsala University Hospital, Dept of Oncol, Radiol and Clin Immunol, Uppsala, Sweden
Background:
Irinotecan with FU/FA is an established regimen in metastatic colorectal cancer, however, with major uncertainties related to the mode of administration of FU. In the US, a weekly bolus schedule, the Saltz regimen, was used extensively, whereas in Europe, infused 5FU is preferred. We have compared irinotecan in combination with either the Nordic fortnightly 5FU/FA
bolus schedule (FLIRI) or the fortnightly Lv5FU2 schedule (FOLFIRI).
Methods:
Between August 2001 and March 2004, 567 previously untreated patients with metastatic colorectal cancer at 27 centres in the Nordic countries were randomized to either FLIRI (irinotecan 180 mg/m2 day 1, 5FU 500 mg/m2 bolus iv day 1, 2, FA 60 mg/m2 day 1,2) or FOLFIRI (irinotecan 180 mg/m2 day 1, FA 200 mg/m2 day 1, 2, 5FU bolus 400 mg/m2 day 1, 2 and infused 5FU 1 200 mg/m2 per 48 hour). The dose of irinotecan, found in a preceding phase II study with the Nordic schedule (210 mg/m2) was lowered after the first 100 randomized patients to 180 mg/m2 because of a slight excess of toxicity (any grade 3-4, 49 vs 38 instances, 60 day mortality 3 vs 2) and concerns seen using the Saltz regimen in two American trials. The primary endpoint was progression-free survival with the aim to show non-inferiority (at the most 20% worse or from median 6.7 to 5.4 months, α=0.05, 1-β=0.80).
Results:
Patient characteristics were well balanced between groups. In the entire patient material, including the first 100 patients, toxicity did not differ between groups (grade 3/4 nausea/vomiting 20 vs 37, diarrhea 23 vs 31, neutropenia 19 vs 8, fever 11 vs 14). The 60 day mortality was 2.4% vs 2.3% (6 patients each in both groups). The primary endpoint, time to progression, did not differ between groups (median 9.1 months in both groups, p = .34).
Conclusions:
Irinotecan with the bolus FU/FA Nordic schedule (FLIRI) is a convenient treatment with efficacy and toxicity comparable to the 'infused' FOLFIRI regimen. Response rates and overall survival will be presented at the meeting.
The work was supported in part by Aventis.