FOLFIRI PLUS CETUXIMAB VERSUS FOLFIRI PLUS BEVACIZUMAB AS FIRST-LINE TREATMENT FOR PATIENTS WITH METASTATIC COLORECTAL CANCER (FIRE-3): A RANDOMIZED, OPEN- LABEL, PHASE 3 TRIAL Ahmed Allam A. Mohamed Assistant Lecturer of Clinical Oncology Assiut University Hospitals
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FIRE 3 Trail FOLFIRI+Cetuximab Vs FOLFIRI+Bevacizumab
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FOLFIRI PLUS CETUXIMAB VERSUS FOLFIRI
PLUS BEVACIZUMAB AS
FIRST-LINE TREATMENT FOR PATIENTS WITH
METASTATIC COLORECTAL
CANCER (FIRE-3): A RANDOMIZED, OPEN-
LABEL, PHASE 3 TRIAL
Ahmed Allam A. MohamedAssistant Lecturer of Clinical Oncology
Assiut University Hospitals
→ The FIRE-3 trial of the Arbeitsgemeinschaft InternistischeOnkologie (AIO),is a two-group, open-label, multicentric,randomized, phase III trial, patients were recruited from Germanyand Austria.
→ sponsored by : Klinikum Großhadern, University of Munich.
→ Funded by : Merck KGaA
→ Recruitment in the trail:• January 23rd 2007: No K-RAS mutation status was required.• October 7th 2008: inclusion was restricted to only patients with
• FDA changedthe labels forPanitumumab- Cetuximabto involvekras exon 2status.
• FDA approval ofCetuximab inadvanced CRC
• aged 18–75 years
• with stage IV, adenocarcinoma of the colon or rectum.
• K-RAS status. !!!!
• an ECOG P.S of 0–2.
• an estimated life expectancy of greater than 3 months.
• adequate organ function (WBC ≥3·0 × 10⁹ /L, neutrophils ≥1·5 × 10⁹ /L, platelets ≥100 × 10⁹ / L and HGB ≥ 9 g/dL, serum bilirubin ≤1·5 × ULN; AST & ALT ≤2·5 × ULN or ≤5 × ULN in the presence of liver metastases, and s.creatinine ≤1·5 × ULN).
• no surgery within the 4 weeks before the start of study treatment.
• The presence of at least one measurable reference lesion according to (RECIST) version 1.09 was also required.
INCLUSION
CRITERIA
• known or suspected brain metastases.• previous treatment with an EGFR-targeting agent or bevacizumab.• previous chemotherapy for colorectal cancer, excluding adjuvant
therapy completed at least 6 months before trial enrolment.• receipt of any experimental drug treatment within 30 days before
enrolment.• clinically relevant coronary heart disease, myocardial infarction within
the past 12 months or a risk of uncontrolled arrhythmia.• acute or subacute intestinal obstruction or a history of chronic infl
ammatory disease or chronic diarrhoea.• symptomatic peritoneal carcinomatosis.• serious, non-healing wounds, ulcers or bone fractures.• uncontrolled hypertension.• pronounced proteinuria (nephrotic syndrome).• arterial thromboembolisms or severe haemorrhages within 6 months
before study enrolment (except a bleeding tumor before tumor resection surgery).
• haemorrhagic diathesis or thrombotic tendency; a pre-existing dihydropyrimidine dehydrogenase defi ciency.
• a pre-existing glucuronidation defect (Gilbert-Meulengrachtsyndrome).
• a history of secondary malignancy within the past 5 years, except for basalioma or carcinoma in situ of the cervix if treated with curative intent.
• or been receiving therapeutic anticoagulation therapy.
Five deaths, all during treatment with FOLFIRI plus bevacizumab, werereported to be related to adverse events:• arrhythmia (1)• Sepsis (1)• thromboembolic event (1)• infection with neutropenia (2).
Two of these deaths (arrhythmia, and infection with neutropenia) were deemed to be related to study treatment.
Death Report During TTT
“The roots of education are bitter, but the fruit is sweet”Aristotle