Analysis Of Efficacy And Safety Baesd On Varied Second-line Treatments And Prognosis Factors Of Relapsed Small Cell Lung Cancer

OBJECTIVE: To study the prognostic factors associated with the progress-free survival(PFS)of patients who received second-line chemotherapy and relapsed within 6 months;to study the difference of disease control rate(DCR),objective response rate(ORR),progression-free survival(PFS)between varied second-line chemotherapy regimens;so that we can get digital and theoretical evidences in some extent for choicing the proper chemotherapy and clinically the proper forecasting of patients with relapsed small cell lung cancer within 6 months.METHODS: The retrospective study was performed in the Shandong Province Cancer Hospital from January 2010 to June 2018,through hospitalizing cases with pathological diagnosis of small cell lung cancer.After haved received etoposide combined with platinum standard first-line treatment,all the patients were confirmed with the disease progression within 6 months.Totally,149 cases of patients with replased small cell lung cancer were collected.Divided 149 cases of patients into 2 groups based on the different second-line chemotherapy: group A(irinotecan combined with platinum regimen),group other(non-irinotecan combined with platinum regimen).If there is statistical difference between the above two groups about observation indicators,then further comparative analysis between group A(irinotecan combined with platinum regimen)with group B(topotecan monotherapy regimen),group C(paclitaxel combined with platinum regimen),group D(docetaxel combined with platinum regimen),group E(liposome paclitaxel combined with platinum regimen)would be conducted then.The progression-free survival time(PFS)of patients with second-line chemotherapy was calculated by Kaplan-Meier method,and the survival curve was plotted in the paper.Unvariate analysis and the COX regression was used to find out the independent predictive factors of PFS after sufferring second-line chemotherapy.Log-rank and Fisher non-parametric tests were used to analyze the DCR,ORR and the distribution of clinical features between varied regimens.The Mann-Whitney was used to compares the occurrence of adverse reactions.P<0.05 was considered to be statistically different.RESULTS: In this study,149 patients with replased small cell lung cancer were treated with first-line therapy(etoposide combined with platinum regimen for 2~6 cycles)and the disease progression was confirmed within 6 months.38 patients confirmed with disease progression after second-line chemotherapy were lost to follow-up,111 patients received third-line treatment or nutritional support or death with disease progression after second-line chemotherapy,respectively.The median PFS of the second-line regimen was 110 days(3.93 months),and the 95% confidence interval was 75.74~144.26 days(2.71~5.15 months).The second-line chemotherapy PFS of replased small cell lung cancer is closely relative with liver metastasis(?2=4.127,P=0.042)and second-line chemotherapy regimen(?2=51.354,P=0.000).The morbidity risk in patients with liver metastasis was 1.718-fold higher than that in patients without liver metastasis.However,both gender(?2=2.333,P=0.127),smoking(?2=2.251,P=0.134),tumor stage(?2=0.325,P=0.569),radiotherapy before second-line chemotherapy(?2 =0.024,P=0.877),KPS score before second-line chemotherapy(?2=1.439,P=0.487),first-line chemotherapy tumor response(?2=1.723,P=0.632),type of recurrence(?2=5.016,P=0.081),brain metastasis(?2=0.228,P=0.633),bone metastases(?2=0.991,P=0.320),adrenal metastasis(?2=0.018,P=0.892),the number of metastases(?2=7.681,P=0.053),malignant pleural effusion(?2=0.002,P=0.967),age(P=0.276),and first-line chemotherapy PFS(P=0.106)were not independent prognostic factors of refractory recurrent small cell lung cancer PFS in second-line chemotherapy.The PFS,ORR and DCR in the second-line chemotherapy regimen of group A were better than group other.There was a statistically significant difference in PFS between group A and group other in the second-line chemotherapy regimen.The HR was 0.235(95% CI: 0.163~0.458),P = 0.000(<0.05).The disease control rate(DCR)of group A and group other were 68.8% and 30.4%,respectively(?2=21.764,P=0.000).And the objective response rate(ORR)was 30.0% and 5.8%,respectively(?2=14.221,P=0.000).Further,the PFS and DCR of the 5 groups of second-line chemotherapy regimen were compared in pairs,and the results showed that the DCR of group A,B,C,D and group E were 68.8%,22.2%,56.3%,14.3%,and 37.5%,respectively.There was significant difference between PFS and DCR in group A,B,D and group E(P<0.05).In a word,second-line chemotherapy PFS and DCR of group A(irinotecan combined with platinum regimen)were better than B(topotecan monotherapy regimen),D(docetaxel combined platinum regimen)and group E(liposome paclitaxel combined with platinum regimen).There was no significant difference in PFS and DCR between group A(the irinotecan combined with platinum regimen)and group C(paclitaxel combined with platinum regimen)as second-line chemotherapy regimens(P=0.264>0.05).There was a statistically significant difference in DCR between group C(paclitaxel and platinum regimen)and group D(docetaxel plus platinum regimen)(P=0.003).It is noticeable that there was a statistical difference between group D(docetaxel combined with platinum regimen)and other groups.The PFS in docetaxel combined with the platinum regimen group is shorter than the other groups.As to adverse reactions,(1)myelosuppression: irinotecan combined with platinum regimen group vs.other groups,the difference was statistically significant(Z=-2.015,P=0.044<0.05).Further,the bone marrow suppressions between the 5 groups based on different second-line chemotherapy regimens were compared.There wre no statistically significant differences in the incidence of myelosuppression(Hc=6.885,P=0.142>0.05).(2)Nausea and vomiting: There were no significant differences in the incidence of vomiting adverse reactions between 5 groups of second-line chemotherapy regimens;(3)diarrhea: diarrhea in the irinotecan combined with platinum regimen was more common than other groups(Z=-3.261,P=0.01).Conclusion: Liver metastasis and second-line chemotherapy regimen are independent influencing factors of second-line chemotherapy PFS in replased small cell lung cancer.In the second-line chemotherapy regimen of Shandong Cancer Hospital,the PFS and DCR of irinotecan combined with platinum regimen,were better than other second-line regimens.Further comparisons in pairs,it showed that the PFS and DCR of the irinotecan combined with the platinum regimen group were superior to the topotecan monotherapy regimen group,docetaxel plus platinum regimen group and paclitaxel liposome combined with the platinum regimen group.There were no differences in the incidence of myelosuppression,nausea and vomiting between the 5 chemotherapy regimens groups.However,the incidence of diarrhea in the irinotecan combined with platinum regimen was significantly higher than other second-line chemotherapy regimens.