Adjuvant Chemotherapy with Chinese Herbal Medicine Formulas Versus Placebo in Patients with Lung Adenocarcinoma after Radical Surgery: a Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial

Qin Wang, Lijing Jiao, Shengfei Wang, Peiqi Chen, Ling Bi, Di Zhou, Jialin Yao, Jiaqi Li, Liyu Wang, Zhiwei Chen, Yingjie Jia, Ziwen Zhang, Weisheng Shen, Weirong Zhu, Jianfang Xu, Yong Gao, Ling Xu, Yabin Gong, Qin Wang, Lijing Jiao, Shengfei Wang, Peiqi Chen, Ling Bi, Di Zhou, Jialin Yao, Jiaqi Li, Liyu Wang, Zhiwei Chen, Yingjie Jia, Ziwen Zhang, Weisheng Shen, Weirong Zhu, Jianfang Xu, Yong Gao, Ling Xu, Yabin Gong

Abstract

Background: The toxicity and side effects caused by adjuvant chemotherapy (ACT) after radical surgery for lung adenocarcinoma (LAC) lead to early termination frequently. This study was conducted to provide an objective basis for the effect of Chinese herbal medicine formulas (CHMFs) combined with chemotherapy in reducing toxicity and enhancing efficacy of ACT.

Method: From February 17th, 2012 to March 20th, 2015, 233 patients from 7 hospitals diagnosed with LAC in IB~IIIA stage were randomly assigned into ACT + CHMF group (116 patients) and ACT + placebo group (117 patients). CHMF was taken orally until the end of chemotherapy. Chemotherapy-related toxic, side effects were investigated as the primary outcome. Disease-free survival (DFS) and overall survival (OS) were used as the secondary outcome.

Results: At one week following chemotherapy, the incidence of dry mouth, diarrhea and thrombocytopenia significantly decreased in CHMF group (P = 0.017, P = 0.033, P = 0.019, respectively). At two weeks following chemotherapy, fatigue and diarrhea were more obvious in the placebo group (P = 0.028, P = 0.025, respectively). In addition, patients in the CHMF group showed an increase in median DFS from 37.1 to 51.5 months compared with placebo group although there was no statistical significance (P = 0.16). In the stage IB subgroup, the CHMF group had a significantly better DFS (HR (95% CI) = 0.53 (0.28-0.99), P = 0.046). There was no significant difference in OS between the groups (P = 0.72).

Conclusion: For patients with LAC, ACT combined with CHMF after radical surgery can prolong the DFS time especially in the early stage, and reduces the chemotherapy-related toxic and side effects.

Trial registration: NCT01441752. Registered 14 July, 2011.

Keywords: Adjuvant chemotherapy; Adverse events; Chinese herbal medicine formulas; Disease-free survival; Lung adenocarcinoma.

Conflict of interest statement

Competing InterestsThe authors declared that they have no competing interests.

© The Author(s) 2020.

Figures

Fig. 1
Fig. 1
Study profile. Data cutoff was April 16, 2018. CHMF, Chinese herbal medicine formula
Fig. 2
Fig. 2
Figures present adverse events which significantly decreased at one week (a) and two weeks (b) following chemotherapy in the CHMF group (solid line) compared with the placebo group (dotted line). * stands for P<0.05
Fig. 3
Fig. 3
Progression-free survival (A-1) and overall survival (B-1) of all patients and patients with stage Ib-IIIa (A/B2–4). Kaplan-Meier estimates of progression-free survival and overall survival as assessed by investigators in populations received adjuvant treatment between CHMF (Red) and placebo (Black) arms. P values were calculated using a two-sided log-rank test. HR, Hazard ratio; CI, confidence interval; CHMF, Chinese herbal medicine formula

References

    1. Siegel RL. Cancer statistics. CA Cancer J Clin. 2018;68:7–30. doi: 10.3322/caac.21442.
    1. Goldstraw P, Chansky K, Crowley J, et al. The IASLC lung cancer staging project: proposals for revision of the TNM stage groupings in the forthcoming (eighth) edition of the TNM classification for lung cancer. J Thorac Oncol. 2016;11(1):39–51. doi: 10.1016/j.jtho.2015.09.009.
    1. Pignon JP, Tribodet H, Scagliotti GV, et al. Lung adjuvant cisplatin evaluation: a pooled analysis by the LACE collaborative group. J Clin Oncol. 2008;26:3552. doi: 10.1200/JCO.2007.13.9030.
    1. Douillard JY, Rosell R, De Lena M, et al. Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB-IIIA non-small-cell lung cancer (adjuvant Navelbine international Trialist association [ANITA]): a randomized controlled trial. Lancet Oncol. 2006;7:719–727. doi: 10.1016/S1470-2045(06)70804-X.
    1. Pisters KM, Evans WK, Azzoli CG, et al. Cancer Care Ontario and American Society of Clinical Oncology adjuvant chemotherapy and adjuvant radiation therapy for stages I-IIIA resectable non-small-cell lung cancer guideline. J Clin Oncol. 2007;25:5506. doi: 10.1200/JCO.2007.14.1226.
    1. National Comprehensive Cancer Network (NCCN). NCCN Clinical practice guidelines in oncology. lung Cancer (Version 3.2011)[DB/OL]. .
    1. Winton T, Livingston R, Johnson D, et al. Vinorelbine plus cisplatin vs observation in resected non-small-cell lung cancer. N Engl J Med. 2005;352:2589–2597. doi: 10.1056/NEJMoa043623.
    1. Wang J, Chen YL, Ping C. Clinical observations on treating 40 cases of locally advanced non-small-cell lung cancer with the Zilongjin tablet. Chin J Trad Chin Med. 2016;8:15–17.
    1. Liang J, Zhang L. Survival effect of Rongyan capsule, a maintenance treatment for advanced non-small-cell lung cancer. Sichuan Zhong Yi. 2013;1:100–101.
    1. Zhao X, Dai X, Wang S. Traditional Chinese medicine integrated with chemotherapy for stage II-IIIA patients with non-small-cell lung cancer after radical surgery: a retrospective clinical analysis with small sample size. Evid Based Complement Alternat Med. 2018;10:1155.
    1. Jiao L, Dong C, Liu J, et al. Effects of Chinese medicine as adjunct medication for adjuvant chemotherapy treatments of non-small cell lung cancer patients. Sci Rep. 2017;7:46524. doi: 10.1038/srep46524.
    1. Wang Q, Jiao L, Wang S, et al. Maintenance chemotherapy with Chinese herb medicine formulas vs. with placebo in patients with advanced non-small cell lung cancer after first-line chemotherapy: a multicenter, randomized, double-blind trial. Front Pharmacol. 2018;9:1233. doi: 10.3389/fphar.2018.01233.
    1. Nakaya S. Question about clinical trial of traditional Chinese medicine. Prog Japanese Med. 2003;24(2):91–93.
    1. Wang R, Luo D, He Z, et al. Objective evaluation of Huoxiang Zhengqi particles placebo. Chin J Exp Tradit Med Formulae. 2014;20(12):91–95.
    1. Scagliotti GV, Pastorino U, Johan F, et al. Randomized phase III study of surgery alone or surgery plus preoperative cisplatin and gemcitabine in stages IB to IIIA non–small-cell lung cancer. J Clin Oncol. 2012;30(2):172–178. doi: 10.1200/JCO.2010.33.7089.
    1. Strauss GM, Herndon JE, Maddaus MA, et al. Adjuvant paclitaxel plus carboplatin compared with observation in stage IB non-small-cell lung cancer: CALGB 9633 with the cancer and leukemia group B, radiation therapy oncology group, and north central cancer treatment group study groups. J Clin Oncol. 2008;26:5043–5051. doi: 10.1200/JCO.2008.16.4855.
    1. Tsao MS, Marguet S, Le Teuff G, et al. Subtype classification of lung adenocarcinoma predicts benefit from adjuvant chemotherapy in patients undergoing complete resection. J Clin Oncol. 2015;58:8335.
    1. Ma M, She Y, Ren Y, et al. Micropapillary or solid pattern predicts recurrence free survival benefit from adjuvant chemotherapy in patients with stage IB lung adenocarcinoma. J Thorac Dis. 2018;10(9):5384–5393. doi: 10.21037/jtd.2018.08.64.
    1. Qian F, Yang W, Wang R, et al. Prognostic significance and adjuvant chemotherapy survival benefits of a solid or micropapillary pattern in patients with resected stage IB lung adenocarcinoma. J Thorac Cardiovasc Surg. 2017;S0022-5223(17):32433–32439.
    1. Fu YL, Tu HB, Dong ZY, et al. Correlation of TCM syndrome types, TNM staging and tumor antigen in lung cancer. World Sci Technol Modern Trad Chin Med. 2015;17(6):1210–1214.

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