Abstract
BackgroundThis study was designed to investigate the efficacy and safety of the epidermal growth factor receptor (EGFR) inhibitor cetuximab combined with irinotecan, folinic acid (FA) and two different doses of infusional 5-fluorouracil (5-FU) in the first-line treatment of EGFR-detectable metastatic colorectal cancer.MethodsThe 5-FU dose was selected on the basis of dose-limiting toxicities (DLTs) during part I of the study. Patients received cetuximab (400 mg/m2 initial dose and 250 mg/m2/week thereafter) and every 2 weeks irinotecan (180 mg/m2), FA (400 mg/m2) and 5-FU (either low dose [LD], 300 mg/m2 bolus plus 2,000 mg/m2 46-hour infusion, n = 7; or, high-dose [HD], 400 mg/m2 bolus plus 2,400 mg/m2; n = 45).ResultsOnly two DLTs occurred in the HD group, and HD 5-FU was selected for use in part II. Apart from rash, commonly observed grade 3/4 adverse events such as leucopenia, diarrhoea, vomiting and asthenia occurred within the expected range for FOLFIRI. Among 52 patients, the overall response rate was 48%. Median progression-free survival (PFS) was 8.6 months (counting all reported progressions) and the median overall survival was 22.4 months. Treatment facilitated the resection of initially unresectable metastases in fourteen patients (27%): of these, 10 patients (71%) had no residual tumour after surgery, and these resections hindered the estimation of PFS.ConclusionThe combination of cetuximab and FOLFIRI was active and well tolerated in this setting. Initially unresectable metastases became resectable in one-quarter of patients, with a high number of complete resections, and these promising results formed the basis for the investigation of FOLFIRI with and without cetuximab in the phase III CRYSTAL trial.
Highlights
This study was designed to investigate the efficacy and safety of the epidermal growth factor receptor (EGFR) inhibitor cetuximab combined with irinotecan, folinic acid (FA) and two different doses of infusional 5-fluorouracil (5-FU) in the first-line treatment of EGFR-detectable metastatic colorectal cancer
Patient characteristics A total of 52 patients were enrolled in the study (23 in part I and 29 in part II) and comprise the ITT and safety populations: seven received LD 5-FU and 45 received HD 5-FU
The second part of the study demonstrated that this combination of cetuximab and the FOLFIRI regimen was associated with promising efficacy and good tolerability in the first-line treatment of metastatic CRC (mCRC)
Summary
This study was designed to investigate the efficacy and safety of the epidermal growth factor receptor (EGFR) inhibitor cetuximab combined with irinotecan, folinic acid (FA) and two different doses of infusional 5-fluorouracil (5-FU) in the first-line treatment of EGFR-detectable metastatic colorectal cancer. Colorectal cancer (CRC) is the third most commonly diagnosed malignancy.[1] In Europe alone in 2006, there were an estimated 412,900 new cases and over 207,000 deaths from the disease.[2] The addition of irinotecan[3,4] or oxaliplatin[5,6] to 5-FU/FA-based regimens, has improved the efficacy of treatment. Combinations of irinotecan and 5-FU/FA have increased overall survival (OS) times to approximately 20 months.[3,4,7,8] These improvements in efficacy, have come at a price of increased toxicity. Diarrhoea and neutropenia are commonly observed with irinotecan-based regimens, they are generally manageable.[3]
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