| General information |
| Database: | DB00912 |
| Objective: | In this study, the maximum tolerated dose and toxicity profile of FOLFIRI (infusional fluorouracil [5FU]/leucovorin/irinotecan) plus gefitinib (an oral inhibitor of the epidermal growth factor receptor) were evaluated as firstline therapy in patients with metastatic colorectal cancer. |
| Authors: | Wolpin BM, et al |
| Title: | Phase I study of gefitinib plus FOLFIRI in previously untreated patients with metastatic colorectal cancer. |
| Journal: | Clin Colorectal Cancer |
| Year: | 2006 |
| PMID: | 17026790 |
| 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: | Phase I study |
| Key Patients Feature: | previously untreated patients with metastatic colorectal cancer. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Oral gefitinib was administered at 250 mg or 500 mg daily in 2 doseescalation cohorts. FOLFIRI was administered without dose escalation on a 14day cycle with treatment on day 1 with irinotecan 180 mg/m2, leucovorin 200 mg/m2, and 5FU 400 mg/m2 bolus, followed by 5FU 2400 mg/m2 continuous infusion over 46 hours. |
| Primary End Point: | maximum tolerated dose and toxicity profile |
| Secondary End Point: | NA |
| Patients Number: | 16 |
| Trial Results |
| DLT_MTD: | The maximum tolerated dose of gefitinibwas 250 mg, with diarrhea and neutropenia noted as the principal doselimiting toxicities |
| Objective Response Rate: | 25% |
| Disease Control Rate: | 81% |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | Gastrointestinal, skin, and hematologic toxicity were the most common adverse.events. Any grade 3/4 toxicity occurred in 12 patients (75%).Diarrhea was the most common grade 3/4 event, occurring in5 of 16 patients (31%). Grade 3/4 neutropenia occurred in 4patients (25%), with 1 episode of febrile neutropenia. No othergrade 3/4 toxicity occurred in > 2 patients. |
| Conclusions: | These findings suggest that gefitinib can be safely combined with FOLFIRI as firstline treatment of metastatic CRC and support the safety of further investigations of EGFR tyrosine kinase inhibitors with multiagent chemotherapy in this patient population. |