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

Kubo,Emi; Yamamoto,Noboru; Nokihara,Hiroshi; Fujiwara,Yutaka; Horinouchi,Hidehito; Kanda,Shintaro; Goto,Yasushi; Ohe,Yuichiro

doi:10.3892/mco.2016.1076

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

Authors:
- Emi Kubo
- Noboru Yamamoto
- Hiroshi Nokihara
- Yutaka Fujiwara
- Hidehito Horinouchi
- Shintaro Kanda
- Yasushi Goto
- Yuichiro Ohe
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Affiliations: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo 104‑0045, Japan
Published online on: November 9, 2016 https://doi.org/10.3892/mco.2016.1076
Pages: 56-62

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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 their EGFR mutation 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.

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