Patient recruitment
This was a multicenter, randomized, open-labelled phase IV trial conducted in 20 hospitals. Recruitment began in October 2014 and ended in May 2016. Written informed consent was obtained from all patients before participation in the trial. A total of 296 patients were randomly divided into the experimental group (n = 148) and the control group (n = 148), using sealed envelopes. Patients in both groups received standard treatment with radiotherapy plus platinum-based chemotherapy.
Eligibility criteria
Patients were eligible for inclusion in the study if they met all of the following inclusion criteria and had none of the listed exclusion criteria.
Inclusion criteria:
(1) before the start of the study, the patients fully understood the research and signed the informed consent form;
(2) age 18–75 years;
(3) pathologically proven lung cancer diagnosis;
(4) according to RECIST (version 1.1), at least one objectively measurable tumor lesion (iconography: computed tomography [CT], magnetic resonance imaging [MRI]) with a diameter > 10 mm (and malignant lymph nodes on CT scans had a diameter > 15 mm);
(5) lung function FEV1 more than at least 1 L and more than 50% A normal value;
(6) basically normal organ function: absolute neutrophil count (ANC) > 1.5 × 109/L, platelet (PLT) count > 100 × 109/L, hemoglobin (Hb) > 9.0 g/dl, total bilirubin (TBIL) level either normal or < 1.5 × the upper limit of normal (ULN), aspartate transaminase (AST [SGOT]) and alanine transaminase (ALT [SGPT]) levels < 2.5 × ULN ( if with liver metastases, < 5 × ULN), and serum creatinine (SCr) < 1.5 × ULN;
(7) expected survival time > 6 months.
Exclusion criteria:
(1) any prior radiotherapy to the lung or mediastinum;
(2) treatment using CKI within 2 weeks before chemoradiotherapy ;
(3) pregnancy or lactation;
(4) severe, uncontrolled organ dysfunction or infection, such as decompensated heart, lung, or kidney failure, which can lead to intolerance of chemotherapy;
(5) participation, current or within the previous 30 days, in other clinical trials;
(6) hypersensitivity to any component of the trial regimen;
(7) history of serious psychological or psychiatric disorders, drug addiction, or alcohol dependence;
(8) and condition making sufficient compliance with this clinical trial unlikely.
Study aims
The primary aim of this study was to observe the incidence and severity of thoracic toxicity during chemoradiotherapy with and without CKI treatment. The secondary aims of this study were to compare clinical symptoms, QoL and adverse drug reactions (ADRs) between the experimental and control groups.
Intervention
Patients in the experimental group received mainline treatments of 250 ml CKI (20 ml diluted in 0.9% normal saline, Shanxi Zhendong Pharmaceutical Co., Ltd., Shanxi, China) daily for 20 continuous days in combination with radiotherapy and chemotherapy. Patients in the control group received only radiotherapy and chemotherapy according to standard guidelines. The follow-up period extended to 4 months after the completion of radiotherapy.
QoL assessment
The European Organization for the Research and Treatment of Cancer Quality of Life (EORTC QLQ-C30)[18], which includes 30 items, was used to evaluate the impact of drugs on patients. According to patients’ answers, the items were scored from 1–4 or 1–7 points. The EORTC QLQ-C30 items are divided into 15 domains, including 5 functional domains, 3 symptomatic domains, 1 life-quality domain, and 6 single items (each one acts as a domain). The raw score (RS) for every domain is the average score of all items in the domain, according to the following formula: RS=(Q1 + Q2+„„+Qn)/n. To compare the scores in every field with each other, we used the range method of linear transformation to transform the RSs into a standard score (SS), which ranged from 0–100. The following formulae for two areas were used (R stands for the score range): functional domain, SS=[1-(RS-1)/R] × 100; and symptomatic and life-quality domains, SS=[(RS-1)/R] × 100.
Safety assessment
Version 4.0 of the Common Terminology Criteria for Adverse Events (CTCAE) [19] issued by the National Cancer Institute (NCI) was used for safety assessment. Liver and kidney function, routine blood analysis, urine, and stool testing, and electrocardiography were completed to assess drug toxicity and adverse reactions in the two groups.
Ethics
This trial was reviewed and approved by the XXXHospital affiliated XXX (approval number: XXX). The trial has been registered in the Chinese Clinical Trial Registry (registration number: XXX).
Statistical analysis
We used SPSS version 20.0 (SPSS, Inc., Chicago, IL, USA) for the statistical analyses. All continuous data are presented as the mean ± standard deviation. Data for the groups were compared using independent sample t-tests. Differences in patient characteristics between the two groups were examined using the t test. Values of p < 0.05 were considered significant.