Cyclooxygenase‑2 inhibitors for non‑small‑cell lung cancer: A phase II trial and literature review

Yokouchi,Hiroshi; Kanazawa,Kenya; Ishida,Takashi; Oizumi,Satoshi; Shinagawa,Naofumi; Sukoh,Noriaki; Harada,Masao; Ogura,Shigeaki; Munakata,Mitsuru; Dosaka-Akita,Hirotoshi; Isobe,Hiroshi; Nishimura,Masaharu

doi:10.3892/mco.2014.319

Cyclooxygenase‑2 inhibitors for non‑small‑cell lung cancer: A phase II trial and literature review

Authors:
- Hiroshi Yokouchi
- Kenya Kanazawa
- Takashi Ishida
- Satoshi Oizumi
- Naofumi Shinagawa
- Noriaki Sukoh
- Masao Harada
- Shigeaki Ogura
- Mitsuru Munakata
- Hirotoshi Dosaka-Akita
- Hiroshi Isobe
- Masaharu Nishimura
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Affiliations: Department of Pulmonary Medicine, Fukushima Medical University, Fukushima 960‑1295, Japan, First Department of Medicine, Hokkaido University School of Medicine, Sapporo, Hokkaido 060‑8648, Japan, Department of Respiratory Medicine, National Hospital Organization Hokkaido Cancer Center, Sapporo, Hokkaido 003‑0804, Japan, Department of Respiratory Disease, Sapporo City General Hospital, Sapporo, Hokkaido 060‑8604, Japan, Department of Medical Oncology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060‑8648, Japan, Department of Medical Oncology, KKR Sapporo Medical Center, Sapporo, Hokkaido 062‑0931, Japan
Published online on: June 19, 2014 https://doi.org/10.3892/mco.2014.319
Pages: 744-750

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Abstract

Several preclinical and clinical studies have demonstrated that cyclooxygenase‑2 (COX‑2) inhibitors are efficient for the treatment of non‑small‑cell lung cancer (NSCLC). However, two recent phase III clinical trials using COX‑2 inhibitors in combination with platinum‑based chemotherapy failed to demonstrate a survival benefit. Thus, validation and discussion regarding the usefulness of COX‑2 inhibitors for patients with NSCLC are required. We conducted a prospective trial using COX‑2 inhibitors for the treatment of 50 NSCLC patients accrued between April, 2005 and July, 2006. Patients with untreated advanced NSCLC received oral meloxicam (150 mg daily), carboplatin (area under the curve = 5 mg̸ml x min on day 1) and docetaxel (60 mg/m2 on day 1) every 3 weeks. The primary endpoint was response rate. The response and disease control rates were 36.0 and 76.0%, respectively. The time‑to‑progression (TTP) and overall survival (OS) were 5.7 months [95% confidence interval (CI): 4.6‑6.7] and 13.7 months (95% CI: 11.4‑15.9), respectively. The 1‑year survival ratio was 56.0%. Grade 3 neuropathy was observed in only 1 patient. We performed tumor immunohistochemistry for COX‑2 and p27 and investigated the correlation between their expression and clinical outcome. COX‑2 expression in the tumor tended to correlate with a higher response rate (50.0% in the high‑ and 18.2% in the low‑COX‑2 group; P=0.092). Based on our results and previous reports, various trial designs, such as the prospective use of COX‑2 inhibitors only for patients with COX‑2‑positive NSCLC, including the exploratory analysis of biomarkers associated with the COX‑2 pathway, may be worth further consideration.

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