Skip to main content
Top
Published in: Cancer Chemotherapy and Pharmacology 6/2014

01-06-2014 | Original Article

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

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

Published in: Cancer Chemotherapy and Pharmacology | Issue 6/2014

Login to get access

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.
Literature
1.
go back to reference Daniels CE, Jett JR (2005) Does interstitial lung disease predispose to lung cancer? Curr Opin Pulm Med 11:431–437PubMedCrossRef Daniels CE, Jett JR (2005) Does interstitial lung disease predispose to lung cancer? Curr Opin Pulm Med 11:431–437PubMedCrossRef
6.
go back to reference 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 PubMedCrossRef 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 PubMedCrossRef
7.
go back to reference 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 30:4357–4361PubMed 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 30:4357–4361PubMed
8.
go back to reference 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 32:5475–5480PubMed 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 32:5475–5480PubMed
9.
go back to reference 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 PubMedCrossRef 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 PubMedCrossRef
10.
go back to reference 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 PubMedCrossRef 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 PubMedCrossRef
12.
go back to reference 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 PubMedCrossRef 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 PubMedCrossRef
13.
go back to reference 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 PubMedCrossRef 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 PubMedCrossRef
14.
go back to reference 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 PubMedCrossRef 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 PubMedCrossRef
15.
go back to reference 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 PubMedCrossRef 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 PubMedCrossRef
16.
go back to reference 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 PubMedCrossRef 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 PubMedCrossRef
17.
go back to reference 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 PubMedCrossRef 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 PubMedCrossRef
18.
go back to reference 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 PubMedCrossRef 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 PubMedCrossRef
19.
go back to reference Boiselle PM, Morrin MM, Huberman MS (2000) Gemcitabine pulmonary toxicity: CT features. J Comput Assist Tomogr 24:977–980PubMedCrossRef Boiselle PM, Morrin MM, Huberman MS (2000) Gemcitabine pulmonary toxicity: CT features. J Comput Assist Tomogr 24:977–980PubMedCrossRef
20.
go back to reference 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 PubMedCrossRef 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 PubMedCrossRef
21.
go back to reference 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 PubMedCrossRef 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 PubMedCrossRef
24.
go back to reference 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 PubMedCrossRef 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 PubMedCrossRef
Metadata
Title
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
Authors
Moon Ki Choi
Jung Yong Hong
Wonjin Chang
Moonjin Kim
Sungmin Kim
Hyun Ae Jung
Su Jin Lee
Silvia Park
Man Pyo Chung
Jong-Mu Sun
Keunchil Park
Myung-Ju Ahn
Jin Seok Ahn
Publication date
01-06-2014
Publisher
Springer Berlin Heidelberg
Published in
Cancer Chemotherapy and Pharmacology / Issue 6/2014
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-014-2458-0

Other articles of this Issue 6/2014

Cancer Chemotherapy and Pharmacology 6/2014 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine