| BackgroundCurrently, the platinum-based2-drug regimens were used as standard chemotherapy regimen for advanced non-small cell lung cancer (NSCLC). However, the overall effectiveness of standard. chemotheray might have reached its peak, with reported median survival time (MST) between6.9-11.3months. At the same time, many severe adverse effects were caused, including nausea and vomiting, immunosuppression and myelosuppression, liver and kidney damage, anemia, neutropenia, thrombocytopenia, hair loss, etc.Recently, molecular targeted drugs, especially EGFR tyrosine kinase inhibitors (EGFR-TKIs), were raised as another approach on the treatment of advanced NSCLC. Gefitinib, one of the EGFR-TKIs, was approved to be used as primary treatment for NSCLC with EGFR mutation. Since the patients with EGFR mutation could benefit much more from EGFR-TKIs than those without EGFR mutation, standard chemotherapy was still suggested to be used for those with unknown or negative status of EGFR mutation. In fact, the advantageous population of gefitinib was limited by the low EGFR mutation rate. In the mainland China, many patients especially the elderly usually refused to receive chemotherapy. The regimens of Chinese medicine and molecular targeted drugs became an important option for such kind of patients.Clinical studies in previous stages showed that the regimen of combining "FuZheng KangAi" decoction with gefitinib might achieve slightly better results than the standard platinum-based chemotherapies for advanced NSCLC, including improved response rates and prolonged survival time."FuZheng KangAi" decoction might also enhance the efficacy of gefitinib, and reduce the adverse effects as well. ObjectiveTo evaluate whether there is noninferiority for the regimen of combining "FuZheng KangAi" decoction with gefitinib, comparing with standard chemotherapy, as a first-line treatment for advanced NSCLC with unknown or negative status of EGFR mutation; so as to provide advanced NSCLC patients with an integrated medicine regimen with higher efficacy and lower toxicity, combining Chinese medicine with molecular targeted drugs. MethodsA prospective, randomized control trial was carried out.66cases of stage IIIB/IV NSCLC with unknown or negative status of EGFR mutation were continuously recruited and randomly divided into experimental group and control group,33cases in each group."FuZheng KangAi" decoction250ml, bid, po, and gefitinib250mg, qd, po,30days for a cycle, were given to the experimental group until the occurrence of disease progression, intolerable adverse effects or death. While platinum-based standard chemotherapy (GP/NP/TP/DP/AP regimen) was given to the control group, repeated every21days for6cycles, or until the occurrence of disease progression, intolerable adverse effects or death. Carboplatin or nedaplatin could be applied instead of cisplatin if cisplatin was not tolerated.Assessments for tumour condition, including chest CT and blood tests, were performed2weeks before the treatment, and after the6th week,3rd&6th month, and every6months afterward. Progression-free survival (PFS) and disease control rate (DCR) were observed and analyzed as the primary endpoints of this clinical trial, while objective response rate (ORR), overall survival (OS), the median survival time (MST), quality of life (QOL) score and toxicity were also observed as the secondary endpoints. ResultsAs of the termination of this trial, there were totally62evaluable cases,31cases for each group. In the experimental group,0cases were evaluated as complete response (CR),4cases as partial response (PR),14cases as stable disease (SD), and13cases as disease progression (PD); ORR was12.90%, DCR was58.06%. In the control group,0cases were evaluated as complete response (CR),6cases as partial response (PR),11cases as stable disease (SD), and14cases as disease progression (PD); ORR was19.35%, DCR was54.84%. The differences between the groups in terms of ORR and DCR were not statistically significant (P>0.05).For the experimental group, the median PFS was5.10months; for the control group, the median PFS was4.17months. The difference between two groups in terms of PFS was not statistically significant (P>0.05).For the experimental group, the MST was9.90months; for the control group, the MST was8.90months. The difference between two groups in terms of OS was not statistically significant (P>0.05).The pre-and post-treatment scores in EORTC QLQ-C30+LC13and FACT-L questionnaires implied that each of the two groups has its own advantages and disadvantages in different dimensions of QOL. A trend of improvement for the experimental group, but deterioration for the control group, was found by contrasting the differences between pre-and post-treatment scores in each group.The incidence of adverse effects in the experimental group was43.75%, mainly grade Ⅰ/Ⅱ diarrhea (21.88%) and acne-like rash (34.38%). The incidence of adverse effects in the control group was81.82%, mainly nausea and vomiting (36.36%), hair loss (27.27%), neutropenia (24.24%), infections (21.21%), liver function abnormalities (18.18%), etc. No cases of severe adverse effects such as interstitial lung disease, dysfunction of heart, liver and kidney, and treatment related death were found in both groups. No withdrawal cases due to adverse effects were reported in this trial. ConelusionIt was found that there were noninferiority and potential advantages for the regimen of "FuZheng KangAi" decoction in combination with gefitinib, comparing with standard chemotherapy, as a first-line treatment for advanced NSCLC with unknown or negative status of EGFR mutation. The regimen of "FuZheng KangAi" decoction with gefitinib brought a similar disease control rate, prolonged survival, and improved quality of life, with mild and tolerable adverse effects. |
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