Background
Methods/design
Study design
Study participants and recruitment
Diagnostic criteria
Syndrome differentiation criteria
Qi deficiency syndrome
-
Major symptoms: cough, a large amount of sputum, loss of appetite, fatigue and weakness, and a pale and bulgy tongue
-
Secondary symptoms: spontaneous perspiration, loose stool, and a thin superficial and smooth pulse
Yin deficiency syndrome
-
Major symptoms: cough, a small amount of sputum, dry mouth, and red tongue
-
Secondary symptoms: night sweats, insomnia, low heat, and a thready and rapid pulse
Qi and Yin deficiency syndrome
-
Major symptoms: cough, a small amount of sputum, fatigue and weakness, and dry mouth without polydipsia
-
Secondary symptoms: spontaneous perspiration, night sweats, a reddish tongue or tongue with teeth imprints, and a thready and weak pulse
Inclusion criteria
Exclusion criteria
Sample size calculation
Randomization
Blinding
Intervention
- IGA: chemotherapy + CHM + LZJ exercises
- IGB: chemotherapy + CHM + rehabilitation education
- CG: chemotherapy + placebo + rehabilitation education
Chemotherapy
- Cisplatin 75–80 mg/m2 on day 1 or carboplatin AUC 5 on day 1; vinorelbine 25–30 mg/m2 on days 1 and 8
- Cisplatin 75–80 mg/m2 on day 1 or carboplatin AUC 5 on day 1; gemcitabine 1250 mg/m2 on days 1 and 8
- Cisplatin 75–80 mg/m2 on day 1 or carboplatin AUC 5 on day 1; docetaxel 75 mg/m2 on day 1
- Cisplatin 75–80 mg/m2 on day 1 or carboplatin AUC 5 on day 1; pemetrexed 500 mg/m2 on day 1 for nonsquamous carcinoma
- Cisplatin 75–80 mg/m2 on day 1 or carboplatin AUC 5 on day 1; paclitaxel 135–175 mg/m2 on day 1
Chinese herbal medicine and placebo
Chinese herbal medicine (CHM)
Syndrome differentiation | Chinese medicine (unit: package) | |||
---|---|---|---|---|
Supplementing Qi granules | Nourishing Yin granules | Supplementing Qi and nourishing Yin granules | Detoxifying and resolving masses granules | |
Qi deficiency | + | – | – | + |
Yin deficiency | – | + | – | + |
Qi and Yin deficiency | – | – | + | + |
Placebo
Liu Zi Jue exercises and rehabilitation education
Liu Zi Jue (LZJ)exercises
Rehabilitation education
Outcome measurement
Primary outcome
-
Quality of life: assessed with the EORTC QOL-LC43. The scoring method will be used to determine the results based on the score changes. Before and after the intervention, the international quality scoring system will be used to calculate the scores of general QoL and various fields.
Secondary outcomes
-
Two-year disease-free survival rate: this rate refers to the percentage of patients without recurrence and metastasis within 2 years after surgery.
-
Disease-free survival (DFS): DFS refers to the interval time from the date of randomization to either the date of the first documented progression or the date of death from any cause, whichever comes first.
-
TCM symptom changes: TCM symptom scores will be recorded and calculated based on the grading scale of lung cancer symptoms required in The Guiding Principles of Clinical Research of New Chinese Medicine treating Primary Bronchial Lung Cancer (2002) issued by National Medical Products Administration. The changes before and after each treatment will be applied for the assessment of efficacy.
-
Physical condition: the physical condition of the patient will be assessed following the ECOG PS standard before and after treatment.
-
Tumor markers: tumor markers, which include CEA, CA-125, and CYFRA21-1, will be measured before and after treatment.
-
Safety and adverse events: according to the Common Terminology Criteria for Adverse Events (CTCAE) V4.0 issued by the National Cancer Institute (NCI) (https://ctep.cancer.gov), all of the patients will be assessed before and after treatment. The evaluation includes hematological and nonhematological adverse events. Complete blood count, hepatic and renal functions, urine and stool routine tests, and electrocardiograms will be measured to assess hematological toxicity. Other adverse events, including toxicity and side effects, of each group will also be recorded and reported during treatment. If there is a serious adverse event (SAE), the treatment will be stopped immediately, and appropriate treatment will be provided. The types and frequencies of adverse events in each group will be reported.