Prognostic effects of osteoclast inhibitors in extensive stage small cell lung cancer patients with bone metastases

Mitsuhashi,Atsushi; Okuma,Yusuke; Zenke,Yoshitaka; Hosomi,Yukio

doi:10.3892/mco.2018.1710

Prognostic effects of osteoclast inhibitors in extensive stage small cell lung cancer patients with bone metastases

Authors:
- Atsushi Mitsuhashi
- Yusuke Okuma
- Yoshitaka Zenke
- Yukio Hosomi
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Affiliations: Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Bunkyo, Tokyo 113‑8677, Japan
Published online on: September 4, 2018 https://doi.org/10.3892/mco.2018.1710
Pages: 561-565

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Abstract

Bone metastases (BM) often induce skeletal‑related events (SREs) and contribute to poor prognoses in patients with cancer. Osteoclast inhibitors (OIs), such as bisphosphonates (BPs) and denosumab, reportedly prevent SREs and improve quality of life in patients with non‑small cell lung cancer and BM, but have not been tested in extensive stage small cell lung cancer (ES‑SCLC) patients. From 238 SCLC patient records, the present study reviewed those of 58 BM patients, including 23 who were treated with OIs (OIs group) and 35 who were untreated (untreated group). Patient backgrounds were balanced between groups using propensity score matching, and survival curves were compared using the log‑rank test. The median overall survival (OS) times were 8.41 and 12.52 months in untreated and OIs groups, respectively, but these did not differ significantly between groups (log‑rank test, P=0.409). The 1‑year OS rate was higher in the OIs group (56.1%) when compared with the control group (22.6%). The results indicated that OIs tend to prolong the short term survival of ES‑SCLC patients with BM. To the best of our knowledge, this is the first study to examine the prognostic effects of OIs in SCLC patients. The results of the present study may highlight the possibility that OIs improve the prognosis of ES‑SCLC patients with BM.

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1	Mundy GR: Metastasis to bone: Causes, consequences and therapeutic opportunities. Nat Rev Cancer. 2:584–593. 2002. View Article : Google Scholar : PubMed/NCBI
2	Coleman RE: Clinical features of metastatic bone disease and risk of skeletal morbidity. Clin Cancer Res. 12:6243s–6249s. 2006. View Article : Google Scholar : PubMed/NCBI
3	Brodowicz T, O'Byrne K and Manegold C: Bone matters in lung cancer. Ann Oncol. 23:2215–2222. 2012. View Article : Google Scholar : PubMed/NCBI
4	Roodman GD: Mechanisms of bone metastasis. N Engl J Med. 350:1655–1664. 2004. View Article : Google Scholar : PubMed/NCBI
5	Serafini AN: Therapy of metastatic bone pain. J Nucl Med. 42:895–906. 2001.PubMed/NCBI
6	Rosen LS, Gordon D, Tchekmedyian NS, Yanagihara R, Hirsh V, Krzakowski M, Pawlicki M, De Souza P, Zheng M, Urbanowitz G, et al: Long-term efficacy and safety of zoledronic acid in the treatment of skeletal metastases in patients with nonsmall cell lung carcinoma and other solid tumors: A randomized, Phase III, double-blind, placebo-controlled trial. Cancer. 100:2613–2621. 2004. View Article : Google Scholar : PubMed/NCBI
7	Zarogoulidis K, Boutsikou E, Zarogoulidis P, Eleftheriadou E, Kontakiotis T, Lithoxopoulou H, Tzanakakis G, Kanakis I and Karamanos NK: The impact of zoledronic acid therapy in survival of lung cancer patients with bone metastasis. Int J Cancer. 125:1705–1709. 2009. View Article : Google Scholar : PubMed/NCBI
8	De Castro J, García R, Garrido P, Isla D, Massuti B, Blanca B and Vázquez J: Therapeutic potential of denosumab in patients with lung cancer: Beyond prevention of skeletal complications. Clin Lung Cancer. 16:431–446. 2015. View Article : Google Scholar : PubMed/NCBI
9	Scagliotti GV, Hirsh V, Siena S, Henry DH, Woll PJ, Manegold C, Solal-Celigny P, Rodriguez G, Krzakowski M, Mehta ND, et al: Overall survival improvement in patients with lung cancer and bone metastases treated with denosumab versus zoledronic acid: Subgroup analysis from a randomized phase 3 study. J Thorac Oncol. 7:1823–1829. 2012. View Article : Google Scholar : PubMed/NCBI
10	Katakami N, Kunikane H, Takeda K, Takayama K, Sawa T, Saito H, Harada M, Yokota S, Ando K, Saito Y, et al: Prospective study on the incidence of bone metastasis (BM) and skeletal-related events (SREs) in patients (pts) with stage IIIB and IV lung cancer-CSP-HOR 13. J Thorac Oncol. 9:231–238. 2014. View Article : Google Scholar : PubMed/NCBI
11	Kang EJ, Lee SY, Kim HJ, Min KH, Hur GY, Shim JJ, Kang KH, Oh SC, Seo JH, Lee SY and Kim JS: Prognostic factors and skeletal-related events in patients with small cell lung cancer with bone metastases at the time of diagnosis. Oncology. 90:103–111. 2016. View Article : Google Scholar : PubMed/NCBI
12	Cetin K, Christiansen CF, Jacobsen JB, Nørgaard M and Sørensen HT: Bone metastasis, skeletal-related events, and mortality in lung cancer patients: A Danish population-based cohort study. Lung Cancer. 86:247–254. 2014. View Article : Google Scholar : PubMed/NCBI
13	Ren Y, Dai C, Zheng H, Zhou F, She Y, Jiang G, Fei K, Yang P, Xie D and Chen C: Prognostic effect of liver metastasis in lung cancer patients with distant metastasis. Oncotarget. 7:53245–53253. 2016. View Article : Google Scholar : PubMed/NCBI
14	Ogino H, Hanibuchi M, Kakiuchi S, Saijo A, Tezuka T, Toyoda Y, Tobiume M, Otsuka K, Sakaguchi S, Goto H, et al: Analysis of the prognostic factors of extensive disease small-cell lung cancer patients in Tokushima University Hospital. J Med Invest. 63:286–293. 2016. View Article : Google Scholar : PubMed/NCBI
15	Goldhirsch A, Joss R, Cavalli F and Brunner KW: Etoposide as single agent and in combination chemotherapy of bronchogenic carcinoma. Cancer Treat Rev. 9:85–90. 1982. View Article : Google Scholar : PubMed/NCBI
16	Evans WK, Osoba D, Feld R, Shepherd FA, Bazos MJ and DeBoer G: Etoposide (VP-16) and cisplatin: An effective treatment for relapse in small-cell lung cancer. J Clin Oncol. 3:65–71. 1985. View Article : Google Scholar : PubMed/NCBI
17	Matsumoto S, Kimura S, Segawa H, Kuroda J, Yuasa T, Sato K, Nogawa M, Tanaka F, Maekawa T and Wada H: Efficacy of the third-generation bisphosphonate, zoledronic acid alone and combined with anti-cancer agents against small cell lung cancer cell lines. Lung Cancer. 47:31–39. 2005. View Article : Google Scholar : PubMed/NCBI
18	Kenessey I, Kói K, Horváth O, Cserepes M, Molnár D, Izsák V, Dobos J, Hegedűs B, Tóvári J and Tímár J: KRAS-mutation status dependent effect of zoledronic acid in human non-small cell cancer preclinical models. Oncotarget. 7:79503–79514. 2016. View Article : Google Scholar : PubMed/NCBI
19	Neville-Webbe HL, Evans CA, Coleman RE and Holen I: Mechanisms of the synergistic interaction between the bisphosphonate zoledronic acid and the chemotherapy agent paclitaxel in breast cancer cells in vitro. Tumour Biol. 27:92–103. 2006. View Article : Google Scholar : PubMed/NCBI
20	Ozturk OH, Bozcuk H, Burgucu D, Ekinci D, Ozdogan M, Akca S and Yildiz M: Cisplatin cytotoxicity is enhanced with zoledronic acid in A549 lung cancer cell line: Preliminary results of an in vitro study. Cell Biol Int. 31:1069–1071. 2007. View Article : Google Scholar : PubMed/NCBI
21	Budman DR and Calabro A: Zoledronic acid (Zometa) enhances the cytotoxic effect of gemcitabine and fluvastatin: In vitro isobologram studies with conventional and nonconventional cytotoxic agents. Oncology. 70:147–153. 2006. View Article : Google Scholar : PubMed/NCBI
22	Fournier PG, Chirgwin JM and Guise TA: New insights into the role of T cells in the vicious cycle of bone metastases. Curr Opin Rheumatol. 18:396–404. 2006. View Article : Google Scholar : PubMed/NCBI
23	Peng X, Guo W, Ren T, Lou Z, Lu X, Zhang S, Lu Q and Sun Y: Differential expression of the RANKL/RANK/OPG system is associated with bone metastasis in human non-small cell lung cancer. PLoS One. 8:e583612013. View Article : Google Scholar : PubMed/NCBI