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Safety and efficacy of gemcitabine or pemetrexed in combination with a platinum in patients with non-small-cell lung cancer and prior interstitial lung disease

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Abstract

Purpose

The incidence of lung cancer in patients with interstitial lung disease (ILD) is higher than in the general population; however, the clinical benefit of chemotherapy and the appropriate regimen for non-small-cell lung cancer (NSCLC) patients with ILD remain unclear. This study was conducted to elucidate the safety and efficacy of palliative chemotherapy with gemcitabine or pemetrexed, both in combination with a platinum agent in NSCLC patients with ILD.

Patients and methods

Patients with advanced or recurrent NSCLC and ILD who received gemcitabine or pemetrexed in combination with a platinum agent as first-line chemotherapy were retrospectively analyzed. Clinical outcomes, including response rate, overall survival (OS), and progression-free survival (PFS), in addition to the acute exacerbation of ILD after chemotherapy were investigated.

Results

Between January 2007 and December 2011, 52 patients were analyzed. The median age at chemotherapy was 67. Thirty-two patients (61.5 %) had adenocarcinoma histology. With respect to the types of ILD, idiopathic interstitial pneumonia (IIP) and non-IIP were observed in 42 (80.8 %) and 10 (19.2 %) patients, respectively. The FEV1 level was less than 80 % of the predicted value in 15 of the 41 patients in whom it was measured. The overall response rate was 42.3 % (95 % CI 28.8–55.9), and the median PFS was 5.4 months (95 % CI 4.6–6.2). The median OS was 7.9 months (95 % CI 5.5–10.3), and the 1-year survival rate was 31.7 % (95 % CI 19.0–44.4). Eight patients (15.4 %) died within 3 months of first-line chemotherapy. Multivariate analysis demonstrated that a heavy smoking history (40 or more pack-year smoking history) was an independent adverse prognostic factor for OS. An acute exacerbation of ILD (AE-ILD) caused by first-line chemotherapy was noted in 5.8 % of patients.

Conclusion

Our results suggest that gemcitabine or pemetrexed in combination with platinum agents could be a feasible option for advanced NSCLC with ILD with some risk of AE-ILD or early death. To establish the efficacy of palliative chemotherapy for patients with NSCLC and ILD, further well-controlled prospective studies are needed.

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References

  1. Daniels CE, Jett JR (2005) Does interstitial lung disease predispose to lung cancer? Curr Opin Pulm Med 11:431–437

    Article  PubMed  Google Scholar 

  2. Samet JM (2000) Does idiopathic pulmonary fibrosis increase lung cancer risk? Am J Respir Crit Care Med 161:1–2. doi:10.1164/ajrccm.161.1.ed14-99

    Article  CAS  PubMed  Google Scholar 

  3. Archontogeorgis K, Steiropoulos P, Tzouvelekis A, Nena E, Bouros D (2012) Lung cancer and interstitial lung diseases: a systematic review. Pulm Med 2012:315918. doi:10.1155/2012/315918

    Article  PubMed Central  PubMed  Google Scholar 

  4. Raghu G, Nyberg F, Morgan G (2004) The epidemiology of interstitial lung disease and its association with lung cancer. Br J Cancer 91(Suppl 2):S3–S10. doi:10.1038/sj.bjc.6602061

    Article  PubMed Central  PubMed  Google Scholar 

  5. Song JW, Hong SB, Lim CM, Koh Y, Kim DS (2011) Acute exacerbation of idiopathic pulmonary fibrosis: incidence, risk factors and outcome. Eur Respir J 37:356–363. doi:10.1183/09031936.00159709

    Article  CAS  PubMed  Google Scholar 

  6. Minegishi Y, Sudoh J, Kuribayasi H, Mizutani H, Seike M, Azuma A, Yoshimura A, Kudoh S, Gemma A (2011) The safety and efficacy of weekly paclitaxel in combination with carboplatin for advanced non-small cell lung cancer with idiopathic interstitial pneumonias. Lung Cancer 71:70–74. doi:10.1016/j.lungcan.2010.04.014

    Article  PubMed  Google Scholar 

  7. Shukuya T, Ishiwata T, Hara M, Muraki K, Shibayama R, Koyama R, Takahashi K (2010) Carboplatin plus weekly paclitaxel treatment in non-small cell lung cancer patients with interstitial lung disease. Anticancer Res 30:4357–4361

    CAS  PubMed  Google Scholar 

  8. Okuda K, Hirose T, Oki Y, Murata Y, Kusumoto S, Sugiyama T, Ishida H, Shirai T, Nakashima M, Yamaoka T, Ohnishi T, Ohmori T (2012) Evaluation of the safety and efficacy of combination chemotherapy with vinorelbine and platinum agents for patients with non-small cell lung cancer with interstitial lung disease. Anticancer Res 32:5475–5480

    CAS  PubMed  Google Scholar 

  9. Watanabe N, Taniguchi H, Kondoh Y, Kimura T, Kataoka K, Nishiyama O, Kondo M, Hasegawa Y (2013) Efficacy of chemotherapy for advanced non-small cell lung cancer with idiopathic pulmonary fibrosis. Respiration 85:326–331. doi:10.1159/000342046

    Article  CAS  PubMed  Google Scholar 

  10. Chiyo M, Sekine Y, Iwata T, Tatsumi K, Yasufuku K, Iyoda A, Otsuji M, Yoshida S, Shibuya K, Iizasa T, Saitoh Y, Fujisawa T (2003) Impact of interstitial lung disease on surgical morbidity and mortality for lung cancer: analyses of short-term and long-term outcomes. J Thorac Cardiovasc Surg 126:1141–1146. doi:10.1016/S0022

    Article  PubMed  Google Scholar 

  11. Saito Y, Kawai Y, Takahashi N, Ikeya T, Murai K, Kawabata Y, Hoshi E (2011) Survival after surgery for pathologic stage IA non-small cell lung cancer associated with idiopathic pulmonary fibrosis. Ann Thorac Surg 92:1812–1817. doi:10.1016/j.athoracsur.2011.06.055

    Article  PubMed  Google Scholar 

  12. Kawasaki H, Nagai K, Yoshida J, Nishimura M, Nishiwaki Y (2002) Postoperative morbidity, mortality, and survival in lung cancer associated with idiopathic pulmonary fibrosis. J Surg Oncol 81:33–37. doi:10.1002/jso.10145

    Article  PubMed  Google Scholar 

  13. Scagliotti GV, Parikh P, von Pawel J, Biesma B, Vansteenkiste J, Manegold C, Serwatowski P, Gatzemeier U, Digumarti R, Zukin M, Lee JS, Mellemgaard A, Park K, Patil S, Rolski J, Goksel T, de Marinis F, Simms L, Sugarman KP, Gandara D (2008) Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol 26:3543–3551. doi:10.1200/JCO.2007.15.0375

    Article  CAS  PubMed  Google Scholar 

  14. Sederholm C, Hillerdal G, Lamberg K, Kolbeck K, Dufmats M, Westberg R, Gawande SR (2005) Phase III trial of gemcitabine plus carboplatin versus single-agent gemcitabine in the treatment of locally advanced or metastatic non-small-cell lung cancer: the Swedish Lung Cancer Study Group. J Clin Oncol 23:8380–8388. doi:10.1200/JCO.2005.01.2781

    Article  PubMed  Google Scholar 

  15. Gronberg BH, Bremnes RM, Flotten O, Amundsen T, Brunsvig PF, Hjelde HH, Kaasa S, von Plessen C, Stornes F, Tollali T, Wammer F, Aasebo U, Sundstrom S (2009) Phase III study by the Norwegian lung cancer study group: pemetrexed plus carboplatin compared with gemcitabine plus carboplatin as first-line chemotherapy in advanced non-small-cell lung cancer. J Clin Oncol 27:3217–3224. doi:10.1200/JCO.2008.20.9114

    Article  PubMed  Google Scholar 

  16. Kim ES, Hirsh V, Mok T, Socinski MA, Gervais R, Wu YL, Li LY, Watkins CL, Sellers MV, Lowe ES, Sun Y, Liao ML, Osterlind K, Reck M, Armour AA, Shepherd FA, Lippman SM, Douillard JY (2008) Gefitinib versus docetaxel in previously treated non-small-cell lung cancer (INTEREST): a randomised phase III trial. Lancet 372:1809–1818. doi:10.1016/S0140-6736(08)61758-4

    Article  CAS  PubMed  Google Scholar 

  17. Hanna N, Shepherd FA, Fossella FV, Pereira JR, De Marinis F, von Pawel J, Gatzemeier U, Tsao TC, Pless M, Muller T, Lim HL, Desch C, Szondy K, Gervais R, Shaharyar, Manegold C, Paul S, Paoletti P, Einhorn L, Bunn PA Jr (2004) Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy. J Clin Oncol 22:1589–1597. doi:10.1200/JCO.2004.08.163

    Article  CAS  PubMed  Google Scholar 

  18. Belknap SM, Kuzel TM, Yarnold PR, Slimack N, Lyons EA, Raisch DW, Bennett CL (2006) Clinical features and correlates of gemcitabine-associated lung injury: findings from the RADAR project. Cancer 106:2051–2057. doi:10.1002/cncr.21808

    Article  CAS  PubMed  Google Scholar 

  19. Boiselle PM, Morrin MM, Huberman MS (2000) Gemcitabine pulmonary toxicity: CT features. J Comput Assist Tomogr 24:977–980

    Article  CAS  PubMed  Google Scholar 

  20. Umemura S, Yamane H, Suwaki T, Katoh T, Yano T, Shiote Y, Takigawa N, Kiura K, Kamei H (2011) Interstitial lung disease associated with gemcitabine treatment in patients with non-small-cell lung cancer and pancreatic cancer. J Cancer Res Clin Oncol 137:1469–1475. doi:10.1007/s00432-011-1013-1

    Article  CAS  PubMed  Google Scholar 

  21. Fujimoto D, Tomii K, Otoshi T, Kawamura T, Tamai K, Takeshita J, Tanaka K, Matsumoto T, Monden K, Nagata K, Otsuka K, Nakagawa A, Hata A, Tachikawa R, Otsuka K, Hamakawa H, Katakami N, Takahashi Y, Imai Y (2013) Preexisting interstitial lung disease is inversely correlated to tumor epidermal growth factor receptor mutation in patients with lung adenocarcinoma. Lung Cancer 80:159–164. doi:10.1016/j.lungcan.2013.01.017

    Article  PubMed  Google Scholar 

  22. Isobe K, Hata Y, Sakamoto S, Takai Y, Shibuya K, Homma S (2010) Clinical characteristics of acute respiratory deterioration in pulmonary fibrosis associated with lung cancer following anti-cancer therapy. Respirology 15:88–92. doi:10.1111/j.1440-1843.2009.01666.x

    Article  PubMed  Google Scholar 

  23. Kim DS, Park JH, Park BK, Lee JS, Nicholson AG, Colby T (2006) Acute exacerbation of idiopathic pulmonary fibrosis: frequency and clinical features. Eur Respir J 27:143–150. doi:10.1183/09031936.06.00114004

    Article  CAS  PubMed  Google Scholar 

  24. Raghu G, Collard HR, Egan JJ, Martinez FJ, Behr J, Brown KK, Colby TV, Cordier JF, Flaherty KR, Lasky JA, Lynch DA, Ryu JH, Swigris JJ, Wells AU, Ancochea J, Bouros D, Carvalho C, Costabel U, Ebina M, Hansell DM, Johkoh T, Kim DS, King TE Jr, Kondoh Y, Myers J, Muller NL, Nicholson AG, Richeldi L, Selman M, Dudden RF, Griss BS, Protzko SL, Schunemann HJ, Fibrosis AEJACoIP (2011) An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med 183:788–824. doi:10.1164/rccm.2009-040GL

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, 135-710, Korea

    Moon Ki Choi, Jung Yong Hong, Wonjin Chang, Moonjin Kim, Sungmin Kim, Hyun Ae Jung, Su Jin Lee, Silvia Park, Jong-Mu Sun, Keunchil Park, Myung-Ju Ahn & Jin Seok Ahn

  2. Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

    Man Pyo Chung

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  1. Moon Ki Choi
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  2. Jung Yong Hong
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Correspondence to Jin Seok Ahn.

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Choi, M.K., Hong, J.Y., Chang, W. et al. Safety and efficacy of gemcitabine or pemetrexed in combination with a platinum in patients with non-small-cell lung cancer and prior interstitial lung disease. Cancer Chemother Pharmacol 73, 1217–1225 (2014). https://doi.org/10.1007/s00280-014-2458-0

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