| General information |
| Database: | DB00911 |
| Objective: | To determine the maximum tolerated doses (MTD), toxicities, efficacy, and pharmacokinetics (PK) of gefitinib combined with irinotecan, 5fluorouracil (5FU) and leucovorin (IFL) in patients with previously untreated advanced colorectal cancer. |
| Authors: | Meyerhardt JA, et al |
| Title: | Phase I study of gefitinib, irinotecan, 5fluorouracil and leucovorin in patients with metastatic colorectal cancer. |
| Journal: | Cancer Chemother Pharmacol. |
| Year: | 2007 |
| PMID: | 17216531 |
| 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, irinotecan, 5fluorouracil + leucovorin |
| Study Type: | Phase I study |
| Key Patients Feature: | patients with previously untreated advanced colorectal cancer |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Starting doses were gefitinib 250 mg/day orally without interruption, irinotecan 100 mg/m(2) as a 90 min intravenous (i.v.) infusion, 5FU 400 mg/m(2) bolus i.v. and leucovorin 20 mg/m(2) i.v. on days 1 and 8 of a 21day cycle. Dose escalations involved increasing gefitinib to 500 mg then increasing irinotecan to 125 mg/m(2) and 5FU to 500 mg/m(2). |
| Primary End Point: | maximum tolerated doses (MTD), toxicities, efficacy, and pharmacokinetics (PK) |
| Secondary End Point: | NA |
| Patients Number: | 24 |
| Trial Results |
| DLT_MTD: | At dose level 1 (gefitinib 250 mg/day, irinotecan 100 mg/m2, bolus 5FU 400 mg/m2, and leucovorin 20 mg/m2), one of the initial three patients experienced a DLT (grade 4 neutropenia). An additional three patients were treated at the same dose level and no further DLTs were detected. dose level 1 was established as the MTD . |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 12.2 months |
| Median OS A vs. C: | 26.6 months |
| Adverse Event(agent arm): | Gastrointestinal effects and bone marrow suppression were the principal toxicities; however, only 1/17 (6%) patients treated with the MTD had severe (grades 34) diarrhea and severe neutropenia occurred in only two (12%) patients. Partial responses occurred in 10/17 patients receiving the MTD and another five had stable disease. |
| Conclusions: | Gefitinib can be safely combined with an intermittent weekly schedule of IFL. Evidence of promising activity should encourage further clinical evaluation of epidermal growth factor receptor tyrosine kinase inhibitors, such as gefitinib, combined with multiagent chemotherapy for metastatic colorectal cancer. |