Chemotherapy in conjunction with traditional Chinese medicine for survival of elderly patients with advanced non-small-cell lung cancer: Protocol for a randomized double-blind controlled trial

doi:10.1016/S2095-4964(14)60028-5

Abstract

Background

Traditional Chinese medicine (TCM) is considered an important complementary therapy with beneficial effects for cancer patients. Elderly patients with non-small-cell lung cancer (NSCLC) are a complex patient group with increasing co-morbidity and shrinking physiological reserve, and may derive substantial benefit from the supportive aspects of TCM. Researchers from Shanghai Longhua Hospital found that qi and yin deficiency is a common syndrome in patients with stage III or IV lung cancer. This project was designed to study the combination of single-agent chemotherapy with TCM methods of benefiting qi and yin in elderly patients with advanced NSCLC.

Methods and design

This is a double-blind controlled, multi-center, and prospective study with randomly selected participants from elderly NSCLC patients in China. Seventy-six patients who meet the inclusion criteria will be allocated into two groups, which will receive treatments of 3-week single-agent chemotherapy with TCM or placebo for four cycles. Progression-free survival (PFS) is the primary end point, and the secondary end points are overall survival, objective response rate, time-to-progression, and quality of life (EORTC QLQ-LC43, and TCM syndrome score). Meanwhile, other end points such as toxicity, side effects and safety of the treatments will be assessed.

Discussion

Results from this study may provide evidence on the effectiveness, and parameters for the usage of single-agent chemotherapy combined with or without TCM on PFS of elderly patients with NSCLC.

Trial Registration

ClinicalTrials.gov. (Identifier: NCT01780181).

Key words: Non-small-cell lung carcinomas, Chemotherapy, Traditional medicine, Chinese, progression-free survival, Randomized controlled trials, Study protocol

Zhi-yi Zhou, Ling Xu, He-gen Li, Jian-hui Tian, Li-jing Jiao, Sheng-fu You, Zhi-fen Han, Yi Jiang, Hui-ru Guo, Hui Liu. Chemotherapy in conjunction with traditional Chinese medicine for survival of elderly patients with advanced non-small-cell lung cancer: Protocol for a randomized double-blind controlled trial. Journal of Integrative Medicine, 2014, 12(3): 175-181.

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URL: http://www.jcimjournal.com/EN/10.1016/S2095-4964(14)60028-5

http://www.jcimjournal.com/EN/Y2014/V12/I3/175

[1]	U.S.National Cancer Institute. Previous version: SEER cancer statistics review, 1975-2010. (2013-06-14)[ 2013-09-06]. .
[2]	Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ . Cancer statistics, 2007[J]. CA Cancer J Clin, 2007,57(1):43-66 doi: 10.3322/canjclin.57.1.43
[3]	Wingo PA, Cardinez CJ, Landis SH, Greenlee RT, Ries LA, Anderson RN, Thun MJ . Long-term trends in cancer mortality in the United States, 1930-1998[J]. Cancer, 2003,97(12 Suppl):3133-3275 doi: 10.1002/(ISSN)1097-0142
[4]	Ruano-Ravina A, Pérez-Becerra R, Fraga M, Kelsey KT, Barros-Dios JM . Analysis of the relationship between p53 immunohistochemical expression and risk factors for lung cancer, with special emphasis on residential radon exposure[J]. Ann Oncol, 2008,19(1):109-114
[5]	Edwards BK, Howe HL, Ries LA, Thun MJ, Rosenberg HM, Yancik R, Wingo PA, Jemal A, Feigal EG . Annual report to the nation on the status of cancer, 1973-1999, featuring implications of age and aging on U.S. cancer burden[J]. Cancer, 2002,94(10):2766-2792 doi: 10.1002/(ISSN)1097-0142
[6]	Owonikoko TK, Ragin CC, Belani CP, Oton AB, Gooding WE, Taioli E, Ramalingam SS . Lung cancer in elderly patients: an analysis of the surveillance, epidemiology, and end results database[J]. J Clin Oncol, 2007,25(35):5570-5577 doi: 10.1200/JCO.2007.12.5435
[7]	Srenson S1, Glimelius B, Nygren P; SBU-group. A systematic overview of chemotherapy effects in non-small cell lung cancer[J]. Acta Oncol, 2001,40(2-3):327-339 doi: 10.1080/02841860120014
[8]	Davidoff AJ, Tang M, Seal B, Edelman MJ . Chemotherapy and survival benefit in elderly patients with non-small-cell lung cancer[J]. J Clin Oncol, 2010,28(13):2191-2197 doi: 10.1200/JCO.2009.25.4052
[9]	Gridelli C, Perrone F, Gallo C, Cigolari S, Rossi A, Piantedosi F, Barbera S, Ferraù F, Piazza E, Rosetti F, Clerici M, Bertetto O, Robbiati SF, Frontini L, Sacco C, Castiglione F, Favaretto A, Novello S, Migliorino MR, Gasparini G, Galetta D, Iaffaioli RV, Gebbia V; MILES Investigators.Chemotherapy for elderly patients with advanced non-small-cell lung cancer: the Multicenter Italian Lung Cancer in the Elderly Study(MILES) phase III randomized trial[J]. J Natl Cancer Inst, 2003,95(5):362-372 doi: 10.1093/jnci/95.5.362
[10]	The Elderly Lung Cancer Vinorelbine Italian Study Group. Effects of vinorelbine on quality of life and survival of elderly patients with advanced non-small-cell lung cancer[J]. J Natl Cancer Inst, 1999,91(1):66-72 doi: 10.1093/jnci/91.1.66
[11]	Ricci S, Antonuzzo A, Galli L, Tibaldi C, Bertuccelli M, Lopes Pegna A, Petruzzelli S, Algeri R, Bonifazi V, Fioretto ML, Orlandini C, Conte PF . Gemcitabine monotherapy in elderly patients with advanced non-small cell lung cancer: a multicenter phase II study[J]. Lung Cancer, 2000,27(2):75-80 doi: 10.1016/S0169-5002(99)00098-7
[12]	Bianco V, Rozzi A, Tonini G, Santini D, Magnolfi E, Vincenzi B , D’Angelillo R, Marchei P.Gemcitabine as single agent chemotherapy in elderly patients with stages III-IV non-small cell lung cancer(NSCLC): a phase II study[J]. Anticancer Res, 2002,22(5):3053-3056
[13]	Pallis AG , Gridelli C, van Meerbeeck JP, Greillier L, Wedding U, Lacombe D, Welch J, Belani CP, Aapro M.EORTC Elderly Task Force and Lung Cancer Group and International Society for Geriatric Oncology(SIOG) experts’ opinion for the treatment of non-small-cell lung cancer in an elderly population[J]. Ann Oncol, 2010,21(4):692-706 doi: 10.1093/annonc/mdp360
[14]	Kudoh S, Takeda K, Nakagawa K, Takada M, Katakami N, Matsui K, Shinkai T, Sawa T, Goto I, Semba H, Seto T, Ando M, Satoh T, Yoshimura N, Negoro S, Fukuoka M . Phase III study of docetaxel compared with vinorelbine in elderly patients with advanced non-small-cell lung cancer: results of the West Japan Thoracic Oncology Group Trial(WJTOG 9904)[J]. J Clin Oncol, 2006,24(22):3657-3663 doi: 10.1200/JCO.2006.06.1044
[15]	Pfister DG, Johnson DH, Azzoli CG, Sause W, Smith TJ, Baker S Jr, Olak J, Stover D, Strawn JR, Turrisi AT, Somerfield MR . American Society of Clinical Oncology treatment of unresectable non-small-cell lung cancer guideline: update 2003[J]. J Clin Oncol, 2004,22(2):330-353 doi: 10.1200/JCO.2004.09.053
[16]	Gridelli C, Aapro M, Ardizzoni A, Balducci L, De Marinis F, Kelly K, Le Chevalier T, Manegold C, Perrone F, Rosell R, Shepherd F, De Petris L, Di Maio M, Langer C . Treatment of advanced non-small-cell lung cancer in the elderly: results of an international expert panel[J]. J Clin Oncol, 2005,23(13):3125-3137 doi: 10.1200/JCO.2005.00.224
[17]	National Collaborating Centre for Acute Care. Lung cancer: the diagnosis and treatment of lung cancer. London: National Institute for Clinical Excellence. 2005.
[18]	Zheng XY. The guiding principles of clinical research of new Chinese medicine (trial). Beijing: Chinese Medical Science and Technology Press. 2002. Chinese.
[19]	Shanghai Municipal Public Health Bureau. Shanghai diagnosis and treatment routine of TCM syndrome. 2nd ed. Shanghai: Shanghai University of Traditional Chinese Medicine Press. 2003. Chinese.
[20]	Wan C, Zhang C, Tu X, Feng C, Tang W, Luo J, Meng Q . Validation of the simplified Chinese version of the quality of life instrument EORTC QLQ-LC43 for patients with lung cancer[J]. Cancer Invest, 2008,26(5):504-510 doi: 10.1080/07357900701781788
[21]	National Cancer Institute. Common terminology criteria for adverse events v3.0 (CTCAE). (2006-08-09)[ 2013-09-06]. .
[22]	Liu JX, Mao L, Yang PL, Qiu JL, Xu LF, Zhao YR, Yu XZ, Xiang RY . Clinical observation on 200 cases of lung cancer patients based on traditional Chinese medicine syndrome differentiation[J]. Zhong Liu Fang Zhi Yan Jiu, 1978,2:48-57
[23]	Liu JX . Treatment of 310 primary lung cancer patients based on traditional Chinese medicine syndrome differentiation[J]. Shanghai Zhong Yi Yao Za Zhi, 1985,10:3-6
[24]	Liu JX, Xu ZY, Shi ZM, Guo YH, Fan ZZ, Li MH, Huang JM, Zhu YW, Zhao LH, Shi CM, Gao H, Chen SX . Strengthening body resistance method in the treatment of 122 patients with advanced non-small cell lung cancer: a prospective study[J]. Zhongguo Yi Yao Xue Bao, 1987,2(1):11-16
[25]	Liu JX . Clinical and experimental research on strengthening body resistance method in the treatment of advanced primary lung adenocarcinoma[J]. Zhong Liu Fang Zhi Yan Jiu, 1990,17(2):129
[26]	Xu ZY, Liu JX, Han MQ, Zhu YW, Zhao LH, Shi ZM, Gao H, Chen SX . Yin-Yang balancing therapy of traditional Chinese medicine for cancer: an effect analysis of 112 cases of advanced cancer patients with more than one year survival[J]. Shanghai Zhong Yi Yao Za Zhi, 1992,3:10-12
[27]	Liu JX, Shi ZM, Xu ZY, Han MQ, Zhu YW, Gao H, Chen SX, Zhao LH, Li HG, Zhu HR, Liu LS . Studies on late primary adenocarcinoma of lung treated by methods of nourishing yin to replenish fluid and warming yang to benefit qi[J]. Zhong Yi Za Zhi, 1995,36(3):155-158
[28]	Liu JX, Pan MQ, Li YH, Ye DX, Guo YH, Li YJ . Clinical study of Jin Fu Kang oral liquid for treating non-small cell lung cancer[J]. Zhong Liu, 2001,21(6):488-491
[29]	Liu JX, Shi ZM, Li HG, Xu ZY, Zhu YW, Zhao LH, Gao H, Liu LS, Zhu HR, Zhang H . Study of Yifei Kangliu decoction for 271 non-small cell lung cancer patients[J]. Yi Xue Yan Jiu Tong Xun, 2003,32(3):23-24
[30]	Guo H, Liu JX, Xu L, Madebo T, Baak JP . Traditional Chinese medicine herbal treatment may have a relevant impact on the prognosis of patients with stage IV adenocarcinoma of the lung treated with platinum-based chemotherapy or combined targeted therapy and chemotherapy[J]. Integr Cancer Ther, 2011,10(2):127-137 doi: 10.1177/1534735410387599
[31]	You J, Shan MJ, Zhao H . Clinical study of integrative treatment for ninety-one elderly patients with advanced non-small cell lung cancer[J]. Zhongguo Zhong Xi Yi Jie He Za Zhi, 2012,32(6):774-778
[32]	Liu LS, Jiang Y, Shen LP, Han ZF, Fan YL, Li HG . Survival analysis of elderly patients with advanced non-small cell lung cancer received traditional Chinese medicine intervention[J]. Shanghai Zhong Yi Yao Da Xue Xue Bao, 2011,25(6):774-778
[33]	Moher D, Hopewell S, Schulz KF, Montori V , G?tzsche PC, Devereaux PJ, Elbourne D, Egger M, Altman DG; Consolidated Standards of Reporting Trials Group.CONSORT 2010 Explanation and Elaboration: Updated guidelines for reporting parallel group randomised trials[J]. J Clin Epidemiol, 2010,63(8):e1-37 doi: 10.1016/j.jclinepi.2010.03.004

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