title: Randomized phase II study of sequential carboplatin plus paclitaxel and gefitinib in chemotherapy-naïve patients with advanced or metastatic non-small-cell lung cancer: Long-term follow-up results.
abstract: The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor gefitinib was initially approved in Japan in 2002 for the treatment of advanced or metastatic non-small-cell lung cancer (NSCLC); however, the optimal order of conventional cytotoxic chemotherapy (carboplatin and paclitaxel) and gefitinib administration has not been determined. We conducted a randomized phase II study of carboplatin and paclitaxel followed by gefitinib vs. gefitinib followed by carboplatin and paclitaxel to select a candidate for further development in a phase III study of chemotherapy-naïve patients with advanced or metastatic NSCLC, regardless of theirEGFRmutation status. A total of 97 patients meeting this description were randomly assigned to arm A (carboplatin and paclitaxel followed by gefitinib; n=49) or B (gefitinib followed by carboplatin and paclitaxel; n=48) from June, 2003 to October, 2005. Carboplatin and paclitaxel were administered in 4 cycles every 3 weeks; gefitinib was continued until disease progression or development of unacceptable toxicity. The primary endpoint was overall survival; the secondary endpoints were response rate and adverse event prevalence. The median overall follow-up was 65.1 months (range, 28.7-75.1 months). The major toxicities were hematological (carboplatin and paclitaxel) or skin rash, diarrhea and hepatic dysfunction (gefitinib). Interstitial lung disease was observed in 1 patient from each arm. In arms A and B, the carboplatin and paclitaxel response rate, gefitinib response rate, and median survival durations were 34.8 and 26.5%, 33.3 and 35.7%, and 18.8 and 17.2 months, respectively. Arm A was selected for a subsequent phase III study.
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan.
authors.forename: Emi
authors.initials: E
authors.lastname: Kubo
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan.
authors.forename: Noboru
authors.initials: N
authors.lastname: Yamamoto
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nokihara
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Fujiwara
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan.
authors.forename: Hidehito
authors.initials: H
authors.lastname: Horinouchi
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Kanda
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Goto
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Ohe
keywords: carboplatin; epidermal growth factor receptor gene mutation; gefitinib; non-small-cell lung cancer; paclitaxel