| General information |
| Database: | DB00774 |
| Objective: | Preclinical studies indicate that gefitinib (Iressa, ZD1839; AstraZeneca, Wilmington, DE), an orally active epidermal growth factor receptor tyrosine kinase inhibitor, may enhance antitumor efficacy of cytotoxics, and combination with paclitaxel and carboplatin had acceptable tolerability in a phase I trial. Gefitinib monotherapy demonstrated unparalleled antitumor activity for a biologic agent, with less toxicity than docetaxel, inphase II trials in refractory, advanced non small cell lung cancer (non small cell lung cancer). Thisphase III, randomized, placebocontrolled, doubleblind trial evaluated gefitinib plus paclitaxel and carboplatin in chemotherapynaive patients with advanced non small cell lung cancer. |
| Authors: | Herbst RS, et al |
| Title: | Gefitinib in combination with paclitaxel and carboplatin in advanced non small cell lung cancer: a phase III trialINTACT 2. |
| Journal: | J Clin Oncol. |
| Year: | 2004 |
| PMID: | 14990633 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | gefitinib
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | non small cell lung cancer |
| Cancer Subtype: | advanced non small cell lung cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | Gefitinib + paclitaxel + carboplatin |
| Study Type: | phase III, randomized, placebocontrolled, doubleblind trial |
| Key Patients Feature: | patients were assessed by physical examination and history to ensure that eligibility criteria were met. Entry criteria included histologically confirmed non small cell lung cancer (cytologic specimens obtained by brushing, washing, or needle aspiration of a defined lesion were acceptable), unresectable stage III or IV disease, no prior chemotherapy, age more than and equal to 18 years, and performance status 0 to 2. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | paclitaxeland carboplatin plus gefitinib 500 mg/d, gefitinib 250 mg/d, or placebo |
| Treatment Info: | Patients received paclitaxel 225 mg/m(2) and carboplatin area under concentration/time curve of 6 mg/min/mL (day 1 every 3 weeks) plus gefitinib 500 mg/d, gefitinib 250 mg/d, or placebo. After a maximum of six cycles, daily gefitinib or placebo continued until disease progression. |
| Primary End Point: | overall survival, time to progression (TTP), response rate (RR), and safety evaluation |
| Secondary End Point: | NA |
| Patients Number: | 1037 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | 30.0%, 30.4%, and 28.7%, respectively, |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 4.6, 5.3, and 5.0 months, respectively in the gefitinib 500 mg/d, gefitinib 250 mg/d, and placebo arms |
| Median OS A vs. C: | 8.7, 9.8, and 9.9 months in the gefitinib 500 mg/d, gefitinib 250 mg/d, and placebo arms, respectively. The 1year survival rates were 37%, 41%, and 42%, respectively. |
| Adverse Event(agent arm): | Most adverse events occurred during combination treatment and many were attributed to chemotherapy. |
| Conclusions: | Gefitinib showed no added benefit in survival, TTP, or RR compared with standard chemotherapy alone. This large, placebocontrolled trial confirmed the favorable gefitinib safety profile observed inphase I and II monotherapy trials. |