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Efficacy Study of Chinese Medicine on Modulating Immune Alterations in Advanced Stage, Non-small Cell Lung Cancer Patients Receiving 1st Line Doublet Chemotherapy and 2nd Line Target Therapy

Phase 2/Phase 3
18 Years
75 Years
Open (Enrolling)
Carcinoma, Non-Small-Cell Lung

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Trial Information

Efficacy Study of Chinese Medicine on Modulating Immune Alterations in Advanced Stage, Non-small Cell Lung Cancer Patients Receiving 1st Line Doublet Chemotherapy and 2nd Line Target Therapy

Lung cancer is the leading cause of mortality and morbidity in the world. In Taiwan, lung
cancer is the second cause of cancer death in men and the first in women. Although the
five-year survival rate in the early stage, operable non-small cell lung cancer patients was
ranged from 60% in stage IA patients to 15% in stage IIIA patients, over 85% of patients
were of advanced and inoperable stage at diagnosis. Their medium survival was around six to
nine months. New generations of chemotherapy or newly developed target therapy can
significantly prolong the medium survival in statistics but the range is only one to three
months, which is of limited significance in clinical practice, suggesting a limitation of
current modalities of treatment. Chinese herbal medicines have a long history and show
effectiveness in benefiting the maintenance of health and the recovery from diseases. Among
them, Astragalus-based Chinese herbs have shown to increase effectiveness of platinum-based
chemotherapy when combined with chemotherapy in advanced stage non-small cell lung cancer.
Despite the fact that many Chinese herbal medicines have shown a pro-apoptotic effect on
tumor cells in vitro, none of them have been demonstrated a tumorocidal effect in clinical
practice, when used alone. Moreover, Astragalus has revealed an anti-apoptotic effect on
cells, suggesting a non-tumorocidal function of Astragalus formula in benefiting cancer

Studies have shown that external or internal stimuli can induce cell transformation. As a
result, dys-regulation in cell growth, DNA repair, cell proliferation and apotosis may
occur. Normal committed tissue cells can transform into undifferentiated, multi-potential
malignant cells. Normally, the competent immune system can recognize the transformed
abnormal cells, undergo immune editing, activate cytotoxic cells to eradicate the abnormal
cells and, finally, prevent malignant cell transformation. But through unknown mechanisms,
the malignant cells may escape from immune surveillance, release chemokines, growth factors
and other mediators to drive the change of inflammatory cells. Consequently, the anti-tumor
function of immune cells is suppressed, leading to an environment in favor of development
and metastasis of malignant cells. From the experiment of animal model and some observations
on malignancy, researchers have suggested that malignant cells can release mediators, which
can activate pre-myeloid suppressors and promote myeloid-derived suppressor cells
development. The myeloid-derived suppressor cells can further trigger cytotoxic T cell
apoptosis, and may shift the macrophages toward M2 subtype, inhibit the Th1 cell, and
initiate other immune suppressive mechanism. The functions of NK cells and regulatory T
cells are altered, resulting in a disturbance of anti-tumor immune function. All these can
further create an environment with a benefit for malignant cell growth and advancement.
Astragalus-based formula may confer its surval advantage in cancer patients through
modulating the immune system and reversing the immunosuppressive microenvironment.

The lung cancer study in the Department of Thoracic Medicine has demonstrated that the
myeloid-derived suppressor cells, cytotoxic T cells, Treg cells and monocytes play a
critically important role in mediating immune alterations in patients with advanced stage,
non-small cell lung cancer. In this three-year proposal, we aim to study the role of one
Astragalus-based formula : Qingshu Yiqi Tang in reversing the immune alterations in patients
with advanced stage, non-small cell lung cancer who receive 1st line doublet chemotherapy of
cisplatin plus doxetaxel(or Pemetrexed for adenocarcinoma)and 2nd line target therapy of
erlotinib. We will target on the modulating effect of Qingshu-Yiqi-Tang on the expression
and function of myeloid-derived suppressor cells, Th1, Th2, cytotoxic T cells, NK cells, and
the subtypes of monocytes (M1-like vs M2-like). Flow cytometry will be used to study the
cell subtypes. The related cytokines and growth factors in serum or supernatant of culture,
including IL4, IL-6, IL13, VEGF, TGFb, GM-CSF, will be analyzed using ELISA and FACS
microbeads array. The expression of iNOS and arginase I will be verified using WB, IP and
RT-PCR. The molecular mechanism related to the cell function will be studied using ex vivo
cell co-culture model. All the patients will be followed up for three years at maximum. We
hope that, via this three-year proposal, we can explore the possible mechanism of the
Astragalus-based formula : Qingshu-Yiqi-Tang(清暑益氣湯) in modulating and reversing
immunosuppression in advanced stage, non-small cell lung cancer patients. Through this
study, we would found a basis for further comprehensive research on the mechanism of other
Chinese herbal medicines for benefiting lung cancer therapy.

Inclusion Criteria:

1. Patients with pathological diagnosis of primary non-small-cell lung cancer Stage

2. Age ≧ 18 years

3. Written, informed consent

4. ECOG: 0-1

Exclusion Criteria:

1. Subjects with inflammatory, infectious or immune disorder, such as TB, AIDS, active
pneumonia, DM, SLE, rheumatoid disease.

2. Subjects with systemic organ disease, such as CHF, ESRD, hepatitis, liver cirrhosis.

3. Subjects with malignancy other than NSCLC.

4. Subjects receiving anti-inflammatory or immunosuppressor medications, such as steroid
(oral, except for chemotherapy premedication, or inhaled), NSAIDs.

5. Patients with no willing to sign the informed consent

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Supportive Care

Outcome Measure:

overall survival

Outcome Time Frame:

3 years

Safety Issue:


Principal Investigator

Tse-Hung Huang, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Chang Gung Memorial Hospital


Taiwan: Institutional Review Board

Study ID:




Start Date:

May 2009

Completion Date:

February 2014

Related Keywords:

  • Carcinoma, Non-Small-Cell Lung
  • chinese medicine
  • non-small cell lung cancer
  • immunosuppression
  • Carcinoma
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms