Abstract
Purpose
Concurrent chemoradiotherapy (CCRT) is one of the standard treatments for patients with advanced head and neck squamous cell carcinoma (HNSCC). However, CCRT may lead to decreased quality of life (QoL) and treatment compliance. This study aimed to determine the effects of PG2 (Astragalus polysaccharides) injection on CCRT-associated adverse events (AEs) and patients’ compliance with the CCRT course.
Methods
In this phase II double-blind randomized placebo-controlled trial, PG2 injection (sterile powder form) or placebo was administrated three times per week in parallel with CCRT to patients with HNSCC. The chemotherapy regimen included 50 mg/m2 cisplatin every 2 weeks with daily tegafur–uracil (300 mg/m2) and leucovorin (60 mg/day).
Results
The study was terminated prematurely due to the successful launch of a newly formulated PG2 injection (lyophilized form). A total of 17 patients were enrolled. The baseline demographics and therapeutic compliance were comparable between the CCRT/PG2 and CCRT/placebo groups. During CCRT, severe treatment-associated AEs were less frequent in the CCRT/PG2 group than in the CCRT/placebo group. Furthermore, less QoL fluctuations from the baseline during CCRT were noted in the CCRT/PG2 group than in the CCRT/placebo group, with a significant difference in the pain, appetite loss, and social eating behavior. The tumor response, disease-specific survival and overall survival did not differ between the two groups.
Conclusion
This preliminary study demonstrated PG2 injection exhibited an excellent safety profile, and has potential in ameliorating the deterioration in QoL and the AEs associated with active anticancer treatment among patients with advanced pharyngeal or laryngeal HNSCC under CCRT. Further research in patients with other cancer types or treatment modalities may widen PG2’s application in clinical settings.
Similar content being viewed by others
Abbreviations
- AE:
-
Adverse event
- CCRT:
-
Concurrent chemoradiotherapy
- CRF:
-
Cancer-related fatigue
- DSS:
-
Disease-specific survival
- FU:
-
Flurouracil
- HNSCC:
-
Head and neck squamous cell carcinoma
- OS:
-
Overall survival
- PLSCC:
-
Pharyngeal or laryngeal squamous cell carcinoma
- PUL:
-
Cisplatin, tegafur plus uracil, and leucovorin
- QoL:
-
Quality of life
References
Bjordal K, de Graeff A, Fayers PM, Hammerlid E, van Pottelsberghe C, Curran D et al (2000) A 12 country field study of the EORTC QLQ-C30 (version 3.0) and the head and neck cancer specific module (EORTC QLQ-H&N35) in head and neck patients. EORTC Quality of Life Group. Eur J Cancer 36(14):1796–1807
Bower JE (2014) Cancer-related fatigue–mechanisms, risk factors, and treatments. Nat Rev Clin Oncol 11(10):597–609. https://doi.org/10.1038/nrclinonc.2014.127
Chao YH, Wu KH, Lin CW, Yang SF, Chao WR, Peng CT, Wu HP (2017) PG2, a botanically derived drug extracted from Astragalus membranaceus, promotes proliferation and immunosuppression of umbilical cord-derived mesenchymal stem cells. J Ethnopharmacol 207:184–191. https://doi.org/10.1016/j.jep.2017.06.018
Chen HW, Lin IH, Chen YJ, Chang KH, Wu MH, Su WH, Lai YL (2012) A novel infusible botanically-derived drug, PG2, for cancer-related fatigue: a phase II double-blind, randomized placebo-controlled study. Clin Invest Med 35(1):E1–E11
Chen CC, Chen X, Li TC, Lin HL, Chu YT, Lee HC, Hsieh CL (2017) PG2 for patients with acute spontaneous intracerebral hemorrhage: a double-blind, randomized, placebo-controlled study. Sci Rep 7:45628. https://doi.org/10.1038/srep45628
Duan P, Wang ZM (2002) Clinical study on effect of Astragalus in efficacy enhancing and toxicity reducing of chemotherapy in patients of malignant tumor. Zhongguo Zhong Xi Yi Jie He Za Zhi 22(7):515–517
Ghi MG, Paccagnella A, Ferrari D, Foa P, Alterio D, Codeca C et al (2017) Induction TPF followed by concomitant treatment versus concomitant treatment alone in locally advanced head and neck cancer. A phase II-III trial. Ann Oncol 28(9):2206–2212. https://doi.org/10.1093/annonc/mdx299
Hsieh CH, Hsu CL, Wang CH, Liaw CC, Chen JS, Chang HK, Wang HM (2013) Cisplatin, tegafur-uracil and leucovorin plus mitomycin C: an acceptably effective and toxic regimen for patients with recurrent or metastatic nasopharyngeal carcinoma. Biomed J 36(5):229–236. https://doi.org/10.4103/2319-4170.113375
Huang PW, Lin CY, Hsieh CH, Hsu CL, Fan KH, Huang SF, Wang HM (2018) A phase II randomized trial comparing neoadjuvant chemotherapy followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in advanced squamous cell carcinoma of the pharynx or larynx. Biomed J 41(2):129–136. https://doi.org/10.1016/j.bj.2018.04.003
Huang WC, Kuo KT, Bamodu OA, Lin YK, Wang CH, Lee KY, Wang LS, Yeh CT, Tsai JT (2019) Astragalus polysaccharide (PG2) ameliorates cancer symptom clusters, as well as improves quality of life in patients with metastatic disease, through modulation of the inflammatory cascade. Cancers (Basel). https://doi.org/10.3390/cancers11081054
Hwang SS, Chang VT, Rue M, Kasimis B (2003) Multidimensional independent predictors of cancer-related fatigue. J Pain Symptom Manage 26(1):604–614
Kuo YL, Chen CH, Chuang TH, Hua WK, Lin WJ, Hsu WH, Huang CY (2015) Gene expression profiling and pathway network analysis predicts a novel antitumor function for a botanical-derived drug, PG2. Evid Based Complement Alternat Med 2015:917345. https://doi.org/10.1155/2015/917345
Li XJJY, Sun YY et al (2008) Clinical efficacy of Astragalus polysaccharide injection combined with chemotherapy for treatment of advanced non-small cell lung cancer. Chin J Clin Oncol 35:919–921
Lou X, Zhang B, Song J et al (2003) Effct of Astragalus polysaccharide in stimulating the secretion of hematopoietic growth factors from activated human PBMC. Tradit Chin Drug Res Clinical Pharmacol 14:310–315
Mendoza TR, Wang XS, Cleeland CS, Morrissey M, Johnson BA, Wendt JK, Huber SL (1999) The rapid assessment of fatigue severity in cancer patients: use of the brief fatigue inventory. Cancer 85(5):1186–1196
Mock V, Atkinson A, Barsevick A, Cella D, Cimprich B, Cleeland C, National Comprehensive Cancer N (2000) NCCN practice guidelines for cancer-related fatigue. Oncology (Williston Park) 14(11A):151–161
Molassiotis A, Potrata B, Cheng KK (2009) A systematic review of the effectiveness of Chinese herbal medication in symptom management and improvement of quality of life in adult cancer patients. Complement Ther Med 17(2):92–120. https://doi.org/10.1016/j.ctim.2008.11.002
Pignon JP, Bourhis J, Domenge C, Designe L (2000) Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: three meta-analyses of updated individual data. MACH-NC Collaborative Group. Meta-analysis of chemotherapy on head and neck cancer. Lancet 355(9208):949–955
Pignon JP, Lemaitre A, Bourhis J, Group, M.-N. C (2007) Meta-analyses of chemotherapy in head and neck cancer (MACH-NC): an update. Int J Radiat Oncol Biol Phys 69(2 Suppl):S112–S114. https://doi.org/10.1016/j.ijrobp.2007.04.088
Shao BM, Xu W, Dai H, Tu P, Li Z, Gao XM (2004) A study on the immune receptors for polysaccharides from the roots of Astragalus membranaceus, a Chinese medicinal herb. Biochem Biophys Res Commun 320(4):1103–1111. https://doi.org/10.1016/j.bbrc.2004.06.065
Silveira AP, Goncalves J, Sequeira T, Ribeiro C, Lopes C, Monteiro E, Pimentel FL (2010) Patient reported outcomes in head and neck cancer: selecting instruments for quality of life integration in clinical protocols. Head Neck Oncol 2:32. https://doi.org/10.1186/1758-3284-2-32
Uwer L, Rotonda C, Guillemin F, Miny J, Kaminsky MC, Mercier M, Conroy T (2011) Responsiveness of EORTC QLQ-C30, QLQ-CR22 and FACT-C quality of life questionnaires in patients with colorectal cancer. Health Qual Life Outcomes 9:70. https://doi.org/10.1186/1477-7525-9-70
Vermorken JB, Remenar E, van Herpen C, Gorlia T, Mesia R, Degardin M et al (2007) Cisplatin, fluorouracil, and docetaxel in unresectable head and neck cancer. N Engl J Med 357(17):1695–1704. https://doi.org/10.1056/nejmoa071028
Vogelzang NJ, Breitbart W, Cella D, Curt GA, Groopman JE, Horning SJ, Portenoy RK (1997) Patient, caregiver, and oncologist perceptions of cancer-related fatigue: results of a tripart assessment survey. The Fatigue Coalition. Semin Hematol 34(3 Suppl 2):4–12
Wang HM, Wang CS, Chen JS, Chen IH, Liao CT, Chang TC (2002) Cisplatin, tegafur, and leucovorin: a moderately effective and minimally toxic outpatient neoadjuvant chemotherapy for locally advanced squamous cell carcinoma of the head and neck. Cancer 94(11):2989–2995. https://doi.org/10.1002/cncr.10570
Wang HM, Hsueh CT, Wang CS, Chen IH, Liao CT, Tsai MH, Chang JT (2005) Phase II trial of cisplatin, tegafur plus uracil and leucovorin as neoadjuvant chemotherapy in patients with squamous cell carcinoma of the oropharynx and hypopharynx. Anticancer Drugs 16(4):447–453
Wang YF, Yang XF, Cheng B, Mei CL, Li QX, Xiao H, Liu K (2010) Protective effect of Astragalus polysaccharides on ATP binding cassette transporter A1 in THP-1 derived foam cells exposed to tumor necrosis factor-alpha. Phytother Res 24(3):393–398. https://doi.org/10.1002/ptr.2958
Wang CH, Lin CY, Chen JS, Ho CL, Rau KM, Tsai JT et al (2019) Karnofsky performance status as a predictive factor for cancer-related fatigue treatment with Astragalus polysaccharides (PG2) injection-a double blind, multi-center. Randomized phase IV study. Cancers (Basel). https://doi.org/10.3390/cancers11020128
Zheng ZP, Yang W, Li N et al (2013) Clinical observation on injection of Astragalus polysaccharides protecting marrow suppression of non-small-cell lung cancer after chemotherapy. Chin Tradit Herbal Drugs 44:208–209
Zou YH, Liu XM (2003) Effect of Astragalus injection combined with chemotherapy on quality of life in patients with advanced non-small cell lung cancer. Zhongguo Zhong Xi Yi Jie He Za Zhi 23(10):733–735
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Ethical approval
Ethical approval was granted by the Institutional Review Board of Chang Gung Memorial Hospital at Linkou, and all procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Informed consent
Informed consent was obtained from all individual participants included in the study.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Hsieh, CH., Lin, CY., Hsu, CL. et al. Incorporation of Astragalus polysaccharides injection during concurrent chemoradiotherapy in advanced pharyngeal or laryngeal squamous cell carcinoma: preliminary experience of a phase II double-blind, randomized trial. J Cancer Res Clin Oncol 146, 33–41 (2020). https://doi.org/10.1007/s00432-019-03033-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00432-019-03033-8