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      Comparison of the benefits of celecoxib combined with anticancer therapy in advanced non-small cell lung cancer: A meta-analysis

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          Abstract

          Background: Studies have reported that advanced NSCLC benefits from celecoxib combined with systematic treatment. However, the optimal combination with different treatments remains unclear. A meta-analysis was conducted to explore treatment combinations.

          Methods: We searched the relevant literature via PubMed, EMBASE, the Cochrane Library and PMC. The data for the overall response rate (ORR), overall survival (OS), progression-free survival (PFS), and adverse effects were obtained. Subgroup analysis was performed according to the treatment pattern. Statistical analyses were carried out using Review Manager 5.3 software.

          Results: A total of 18 eligible studies were included, with 1178 advanced NSCLC patients. Subgroup analysis revealed that celecoxib combined with chemotherapy or tyrosine kinase inhibitors (TKIs) significantly increased the ORR, with no significant difference between the two groups. Celecoxib combined with chemotherapy improved OS-6 (OR=0.65, 95% CI 0.59-0.71, P<0.001), while OS-6 was not changed with celecoxib combined with TKIs (OR=0.53, 95% CI 0.31-0.73, P=0.82). Differences were apparent between the chemotherapy and TKIs regarding OS-6 (P=0.0392). Celecoxib combined with chemotherapy significantly prolonged OS-12 (OR=0.39, 95% CI 0.33-0.45, P<0.001). In terms of OS-12, there was no significant improvement when celecoxib was combined with radiotherapy or TKIs. Celecoxib combined with chemotherapy or TKIs significantly improved PFS-6 and PFS-12, with no obvious difference in terms of PFS between the two groups. Additionally, celecoxib combined with chemotherapy or TKI treatment increased the incidence of adverse events, with no significant differences between the two groups.

          Conclusions: Celecoxib combined with chemotherapy or TKIs improved the ORR, with no significant differences between the two groups. In terms of OS, celecoxib combined with chemotherapy was superior to TKIs or radiotherapy. Accordingly, celecoxib combined with chemotherapy increased hematological toxicity and cardiovascular events.

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          ROS1 rearrangements define a unique molecular class of lung cancers.

          Kristin Bergethon, Alice Shaw, Sai-Hong Ignatius Ou … (2012)
          Chromosomal rearrangements involving the ROS1 receptor tyrosine kinase gene have recently been described in a subset of non-small-cell lung cancers (NSCLCs). Because little is known about these tumors, we examined the clinical characteristics and treatment outcomes of patients with NSCLC with ROS1 rearrangement. Using a ROS1 fluorescent in situ hybridization (FISH) assay, we screened 1,073 patients with NSCLC and correlated ROS1 rearrangement status with clinical characteristics, overall survival, and when available, ALK rearrangement status. In vitro studies assessed the responsiveness of cells with ROS1 rearrangement to the tyrosine kinase inhibitor crizotinib. The clinical response of one patient with ROS1-rearranged NSCLC to crizotinib was investigated as part of an expanded phase I cohort. Of 1,073 tumors screened, 18 (1.7%) were ROS1 rearranged by FISH, and 31 (2.9%) were ALK rearranged. Compared with the ROS1-negative group, patients with ROS1 rearrangements were significantly younger and more likely to be never-smokers (each P < .001). All of the ROS1-positive tumors were adenocarcinomas, with a tendency toward higher grade. ROS1-positive and -negative groups showed no difference in overall survival. The HCC78 ROS1-rearranged NSCLC cell line and 293 cells transfected with CD74-ROS1 showed evidence of sensitivity to crizotinib. The patient treated with crizotinib showed tumor shrinkage, with a near complete response. ROS1 rearrangement defines a molecular subset of NSCLC with distinct clinical characteristics that are similar to those observed in patients with ALK-rearranged NSCLC. Crizotinib shows in vitro activity and early evidence of clinical activity in ROS1-rearranged NSCLC.
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            Antiangiogenic and antitumor activities of cyclooxygenase-2 inhibitors.

            Larry S. Zweifel, B Mark Woerner, Alane T Koki … (2000)
            We provide evidence that cyclooxygenase (COX)-2-derived prostaglandins contribute to tumor growth by inducing newly formed blood vessels (neoangiogenesis) that sustain tumor cell viability and growth. COX-2 is expressed within human tumor neovasculature as well as in neoplastic cells present in human colon, breast, prostate, and lung cancer biopsy tissue. COX-1 is broadly distributed in normal, as well as in neoplastic, tissues. The contribution of COX-2 to human tumor growth was indicated by the ability of celecoxib, an agent that inhibits the COX-2 enzyme, to suppress growth of lung and colon tumors implanted into recipient mice. Mechanistically, celecoxib demonstrated a potent antiangiogenic activity. In a rat model of angiogenesis, we observe that corneal blood vessel formation is suppressed by celecoxib, but not by a COX-1 inhibitor. These and other data indicate that COX-2 and COX-2-derived prostaglandins may play a major role in development of cancer through numerous biochemical mechanisms, including stimulation of tumor cell growth and neovascularization. The ability of celecoxib to block angiogenesis and suppress tumor growth suggests a novel application of this anti-inflammatory drug in the treatment of human cancer.
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              Phase II Study of Crizotinib in East Asian Patients With ROS1-Positive Advanced Non–Small-Cell Lung Cancer

              Takashi Seto, Jianying Zhou, James Yang … (2018)
              Article 0 comments Cited 110 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Cancer
                Journal ID (iso-abbrev): J Cancer
                Journal ID (publisher-id): jca
                Title: Journal of Cancer
                Publisher: Ivyspring International Publisher (Sydney )
                ISSN (Electronic): 1837-9664
                Publication date Collection: 2020
                Publication date (Electronic): 20 January 2020
                Volume: 11
                Issue: 7
                Pages: 1816-1827
                Affiliations
                Department of Oncology, Zhujiang Hospital, Southern Medical University, 253 Industrial Avenue, Guangzhou, 510282, Guangdong, People's Republic of China.
                Author notes
                ✉ Corresponding authors: Peng Luo and Jian Zhang, Department of Oncology, Zhujiang Hospital, Southern Medical University, 253 Industrial Avenue, Guangzhou, 510282, Guangdong, People's Republic of China. Affiliation: Department of Oncology, Zhujiang Hospital, Southern Medical University. ORCID numbers: 0000-0001-7217-0111 (Jian Zhang), 0000-0002-8215-2045 (Peng Luo). Email: blacktiger@ 123456139.com (Jian Zhang), luopeng@ 123456smu.edu.cn (Peng Luo). Tel: 0086-13925091863; Fax: +86 020-61643888.

                *Wei Zhang and Lilan Yi contributed equally to this study and should be considered as co-first authors.

                Competing Interests: The authors have declared that no competing interest exists.

                Article
                Publisher ID: jcav11p1816
                DOI: 10.7150/jca.35003
                PMC ID: 7052875
                SO-VID: 2970dc23-2860-4b6c-bb19-582a43563fde
                Copyright © © The author(s)
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.

                History
                Date received : 18 March 2019
                Date accepted : 14 November 2019
                Categories
                Subject: Research Paper

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: celecoxib,non-small cell lung cancer,comprehensive therapy,meta-analysis
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: celecoxib, non-small cell lung cancer, comprehensive therapy, meta-analysis

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