Objective:

2

To investigate whether the combination of chemotherapy with staged Chinese herbal medicine (CHM) therapy could enhance health-related quality of life (QoL) in non-small-cell lung cancer (NSCLC) patients and prolong the time before deterioration of lung cancer symptoms

in comparison to chemotherapy alone.

Methods:

2

A prospective

double-blind

randomized

controlled trial was conducted from December 14

2017 to August 28

2020. A total of 180 patients with stage ⅠB–ⅢA NSCLC from 5 hospitals in Shanghai were randomly divided into chemotherapy combined with CHM (chemo+CHM) group (120 cases) or chemotherapy combined with placebo (chemo+placebo) group (60 cases) using stratified blocking randomization. The European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life-Core 30 Scale (QLQ-C30) was used to evaluate the patient-reported outcomes (PROs) during postoperative adjuvant chemotherapy in patients with early-stage NSCLC. Adverse events (AEs) were assessed in the safety analysis.

Results:

2

Out of the total 180 patients

173 patients (116 in the chemo+CHM group and 57 in the chemo+placebo group) were included in the PRO analyses. The initial mean QLQ-C30 Global Health Status (GHS)/QoL scores at baseline were 57.16±1.64 and 57.67±2.25 for the two respective groups (

P

>

0.05). Compared with baseline

the chemo+CHM group had an improvement in QLQ-C30 GHS/QoL score at week 18 [least squares mean (LSM) change 17.83

95% confidence interval (CI) 14.29 to 21.38

]

. Conversely

the chemo+placebo group had a decrease in the score (LSM change –13.67

95% CI –22.70 to –4.63). A significant between-group difference in the LSM GHS/QoL score was observed

amounting to 31.63 points (95% CI 25.61 to 37.64

P

<

0.001). The similar trends were observed in physical functioning

fatigue and appetite loss. At week 18

patients in the chemo+CHM group had a higher proportion of improvement or stabilization in GHS/QoL functional and symptom scores compared to chemo+placebo group (

P

<

0.001). The median time to deterioration was longer in the chemo+CHM group for GHS/QoL score [hazard ratio (HR)=0.33

95% CI 0.23 to 0.48

P

<

0.0010

]

physical functioning (

HR

=0.43

95% CI 0.25 to 0.75

P

=0.0005)

fatigue (

HR

=0.47

95% CI 0.30 to 0.72

P

<

0.0001) and appetite loss (

HR

=0.65

95% CI 0.42 to 1.00

P

=0.0215). The incidence of AEs was lower in the chemo+CHM group than in the chemo+placebo group (9.83%

vs

. 15.79%

P

=0.52).

Conclusion:

2

The staged CHM therapy could help improve the PROs of postoperative patients with early-stage NSCLC during adjuvant chemotherapy

which is worthy of further clinical research. (Registry No. NCT03372694)