| General information |
| Database: | DB00929 |
| Objective: | Gefitinib inhibits the epidermal growth factor receptor tyrosine kinase and preclinical studies indicate that it may enhance CPT11 cytotoxicity. This randomizedphase II trial investigates the feasibility and efficacy of gefitinib and 5fluorouracil, folinic acid, irinotecan (FOLFIRI) in patients with metastatic colorectal cancer |
| Authors: | Santoro A, et al |
| Title: | a phase II randomized multicenter trial of gefitinib plus FOLFIRI and FOLFIRI alone in patients with metastatic colorectal cancer. |
| Journal: | Ann Oncol. |
| Year: | 2008 |
| PMID: | 18667394 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | gefitinib
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | colorectal cancer |
| Cancer Subtype: | advanced colorectal cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | gefitinib + FOLFIRI |
| Study Type: | a phase II randomized multicenter trial |
| Key Patients Feature: | histologically confirmed metastatic adenocarcinoma of the colon or rectum with measurable lesions according to RECIST, life expectancy of at least 12 weeks, age >18 years and Eastern Cooperative Oncology Group performance status of zero or one. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | gefitinib plus FOLFIRI versus FOLFIRI alone |
| Treatment Info: | patients were randomized to FOLFIRI +/ gefitinib 250 mg daily p.o. Patients randomized to FOLFIRI + gefitinib without disease progression after 6 months continued to receive gefitinib alone until disease progression |
| Primary End Point: | efficacy and safety |
| Secondary End Point: | NA |
| Patients Number: | 100 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | 47.9% in the FOLFIRI arm and 45.1% in the FOLFIRI + gefitinib arm |
| Disease Control Rate: | 81.8% overall, 83.3% in the FOLFIRIalone arm and 80.4% in the FOLFIRI plus gefitinib arm |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 8.3 months in the FOLFIRI arm, and 8.3 months in the FOLFIRI + gefitinib arm |
| Median OS A vs. C: | 18.6 months in the FOLFIRI arm, and 17.1 months in the FOLFIRI + gefitinib arm |
| Adverse Event(agent arm): | The toxicity of the combination of FOLFIRI plus gefitinib was acceptable although drugrelated NCICTC grades 3-4 adverse events were experienced by 35 (68.6%) patients randomized to FOLFIRI plus gefitinib arm compared with 25 patients (52.1%) in the FOLFIRIalone arm, serious adverse events by 13 (25.5%) patients randomized to FOLFIRI plus gefitinib arm versus 10 patients (20.8%) in the FOLFIRIalone arm (Table 4). Most common drugrelated NCICTC grades 3-4 adverse events included diarrhea (33.3% of patients in the FOLFIRI plus gefitinib arm versus 2.1% in the FOLFIRIalone arm) and neutropenia (35.3% of patients in the FOLFIRI plus gefitinib arm versus 22.9% in the FOLFIRIalone arm) |
| Conclusions: | These data show that adding gefitinib to FOLFIRI does not improve the efficacy of FOLFIRI regimen. These disappointing results could be related to the high toxicity observed that led to significant dose reductions and delays |