| Objective: The use of chemoradiotherapy for limited-stage small cell lung cancer(SCLC) can achieve good effect, but it is very likely to have metastasis and result in poor prognosis. This study retrospectively analyzes the follow-up treatments of limited-stage SCLC patients after receiving standard chemoradiotherapy in order to explore whether maintenance therapy with etoposide alone can further effectively control tumor and extend progression free survival(PFS) and overall survival(OS) of patients, and to analyze the feasibility and safety of this therapy in clinic.Methods: A total of 148 cases, who were diagnosed of with limited-stage SCLC at The Second People’s Hospital of Hengshui and The Fourth People’s Hospital of Hengshui from March 2003 to January 2012 and obtained benefits from standard EP program and local radiotherapy(CR+PR+SD), were enrolled in this study. These patients were divided into two groups: the maintenance treatment group continued to orally took topside capsules(50mg/m2/d; d1-10; a 21-day cycle); the control group received the best supportive treatment after chemoradiotherapy. The maintenance treatment group was evaluated for curative effect every 6 weeks, while the control was evaluated for every 2 months. Curative effect evaluations as well as adverse reactions were recorded in detail until tumor progression or adverse reactions could not be tolerated. Follow-up records were made for PFS of patients.Using SPSS21.0 statistical software, this study analyzed PFS, OS and KPS score(Karnofsky Performance Score), and adverse reactions after chemotherapy. PFS and OS of patients were calculated with Kaplan-Meier method, and survival curves were prepared accordingly. A single factor analysis was conducted with Kaplan-Meier method, COX proportional hazard model multivariate analysis was performed, and Log-rank test were used to test the significance(P<0.05).Results: 1 Baseline dataAmong the 148 cases enrolled, there were 72 cases in the treatment group and 76 cases in the control group. There were no statistically differences in gender, age and KPS score between the two groups, and their distributions in the two groups were balanced basically(P > 0.05). The median treatment cycle was 5(3~8 cycles) in the maintenance group, 2 cases in which received low dose therapy, accounting for 2.8% of the total number. 2 Effect and Survival Analysis 2.1 PFS AnalysisThe median PFS in the treatment group was 13.0 months(95%CI=12.4~13.6 months), while that in the control was 10.0 months(95%CI=9.3~10.7 months). Log-rank test was employed to compared the survival curves of the two groups, and the result showed a statistically significant difference(χ2=26.361, P=0.000). PFS in the treatment group was higher than the control. Preliminary analysis indicated that maintenance treatment could extend PFS in the treatment group.There were 27 cases with less than 4 cycles of maintenance treatment(median PFS=9.0 months)(95%CI=8.3~9.7 months), and 45 cases with 4(or above) cycles of maintenance treatment(median PFS=13.0 months)(95%CI=12.3~13.7). There was a statistically significant difference in PFS between the two groups(χ2=6.724, P=0.010). 2.2 OS AnalysisThe 1, 2 and 3 year OS rates in the treatment group were 79.2%, 44.4% and 22.1%(median OS=24.0 months)(95%CI=20.3~27.7 months); The 1, 2 and 3 year OS rates in the control group were 69.7%, 31.6% and 15.8%(median OS=18.0 months)(95%CI=14.6~21.4 months). Log-rank test was carried out to compare the survival curves of the two groups, showing a statistically significant difference(χ2=9.568, P=0.002). The OS in the experiment group was higher than the control group, suggesting that maintenance treatment can extend OS of patients. 2.3 PFS Influence FactorSingle factor analysis showed that treatment mode(with or without maintenance treatment)(OR=2.149, P=0.000), KPS score(OR=0.638, P=0.020) and PCI(pro-phylactic cranial irradation)(R=1.900, P=0.003) had significant correlations with PFS. COX regression multivariate analysis showed that treatment mode(OR=2.326, P=0.000), KPS score(OR=0.600, P=0.009) and PCI(OR=2.051, P=0.001) were independent influencing factors for PFS.OS Influence FactorSingle factor analysis showed that treatment mode(with or without maintenance treatment)(OR=1.676, P=0.003), KPS score(OR=0.514, P=0.001) and PCI(pro-phylactic cranial irradation)(R=2.030,P=0.001) had significant correlations with OS. COX regression multivariate analysis showed that treatment mode(OR=1.882, P=0.001), KPS score(OR=0.475, P=0.000) and PCI(OR=1.999, P=0.001) were independent influencing factors for OS. 3 Therapeutic Safety and Tolerance 3.1 KPS Score AnalysisThe performance statuses(improvement and stabilization)in the maintenance treatment group and the control group were respectively 69.4% and 72.4%, showing no statistically significant difference(χ2=0.153, P=0.695). Compared with the control group, KPS score in patients undergoing maintenance treatment in the experiment group had no obvious change, as is the case with performance status. 3.2 Adverse ReactionsThe major adverse reactions in this study include bone marrow suppression, impairments of hepatorenal function and gastrointestinal reaction. Most of them were I~II degree reactions, while III~IV degree reaction had a low incidence rate and could be relieved and tolerated by patients after proper treatment. There were no death cases caused by severe adverse reactions.Hematological adverse reactions mainly included the decrease of leukocyte count, followed by the decrease of platelet count and hemoglobin count. The occurrence rate of leukocyte decline in the experiment group was 41.6%, and there were 25 cases with I~II degree reaction(34.7%), 5 cases with III~IV degree reaction(6.9%); the occurrence rate of leukocyte decline in the control group was 19.7%, and there were 13 cases with I~II degree reaction(17.1%) and 2 cases with Ⅲ- Ⅳdegree reaction(2.6%). And the occurrence rate of leukocyte decline in the experiment group was much higher than that of the control group(χ2=8.403, P=0.004). There were 26 cases with hemoglobin decline(36.1%) in the experiment group and 10 cases with hemoglobin decline(13.2%) in the control group, and both were I~ degree Ⅱanemia. And the occurrence rate of hemoglobin decline in the experiment group was much higher than that of the control group(χ2=10.582, P=0.001). In terms of platelet decline, there were 6 cases with I~ Ⅱdegree platelet decline(8.3%) in the experiment group and no platelet decline in the control group, showing a statistically significant difference(χ2=6.601, P=0.010).Impairments of hepatorenal function were mainly characterized by the elevated SGPT level, as well as the elevated levels of bilirubin, alkaline phosphatase, urea nitrogen, and creatinine. There were 4 cases with I~ Ⅱdegree elevated SGPT level(5.6%) and 1 case with Ⅲ- Ⅳdegree elevated SGPT level(1.4%) in the experiment group; there were 4 cases with I~ Ⅱdegree increased level of SGPT(5.3%) in the control group. The occurrence rate of elevated SGPT level in the experiment group was higher than that in the control group, showing no statistically significant difference(χ2=0.467, P=0.495). All other impairments of hepatorenal function were I~ Ⅱdegree, and these impairments in the experiment group were higher than those in the control group. However, all indexes returned to normal after proper treatment.Non-hematological adverse reactions mainly include gastrointestinal reactions such as nausea, vomiting and diarrhea, all of which were I~ Ⅱdegree. These reactions in the experiment group were higher than those in the control group. However, all indexes returned to normal after proper treatment.Conclusions:1 The oral administration of etoposide capsules in maintenance treatment for patients with limited-stage SCLC who remain in stable condition after receiving conventional treatment may extend their PFS and OS and bring more benefits to them after more than 4 cycles.2 The oral administration of etoposide capsules in maintenance treatment for patients with limited-stage SCLC causes more adverse reactions, but they are well within patients’ tolerance ranges, thus having better safety.3 According to the clinical data analysis of 148 cases, COX regression multivariate analysis demonstrates that treatment mode, PCI and KPS score(80~100 points) are influence factors for better prognoses of PFS and OS. |
PDF Full Text Request