依托泊苷及伊立替康联合铂类化疗对广泛期小细胞肺癌的疗效及安全性分析
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摘要
目的对比广泛期小细胞肺癌(small cell lung cancer,SCLC)采用依托泊苷联合铂类化疗(etoposide plus platinum,EP)与伊立替康联合铂类化疗(irinotecan plus platinum,IP)两种方案的疗效及安全性。方法回顾性分析2013-2017年陆军军医大学第三附属医院收治的144例SCLC患者,其中一线接受EP方案化疗65例(EP组),一线接受IP方案化疗79例(IP组)。对比EP组和IP组疗效及安全性,分析放疗及淋巴细胞亚群对生存的影响。结果 EP组和IP组客观缓解率(objective response rate,ORR)分别为67.7%(44/65)、57.0%(45/79),差异无统计学意义(P=0.243);EP组和IP组中位无进展生存期(median progression-free survival,m PFS)、中位生存时间(median overall survival,m OS)无明显差异(5.05 vs 4.30个月,P=0.650;13.95 vs 14.10个月,P=0.120)。无论EP组还是IP组,联合胸部放疗均可以显著延长m PFS及m OS。淋巴细胞亚群T4、T8总数降低患者m PFS、m OS明显低于淋巴细胞亚群T4、T8总数正常者。3/4级以上毒副反应方面:IP组腹泻发生率为46.8%,显著高于EP组(7.7%,P=0.020);EP组中性粒细胞减少发生率为52.3%,显著高于IP组(22.8%,P=0.001);EP组贫血发生率为73.8%,显著高于IP组(40.5%,P=0.013)。结论对于SCLC患者,EP方案与IP方案疗效无明显差异,联合胸部放疗可显著改善患者预后,淋巴细胞亚群中T4、T8总数正常患者较低下患者预后好,EP组中性粒细胞减少及贫血发生率高,IP组腹泻发生率高。
Objective To compare the efficacy and safety of etoposide plus platinum(EP) and irinotecan plus platinum(IP) regimens for treatment of extensive-stage small cell lung cancer(SCLC).Methods This retrospective study was conducted among 144 patients with extensive-stage SCLC receiving chemotherapy with EP regimen(65 cases) or IP regimen(79 cases) in our hospital during the period from2013 to 2017.Twenty-two patients in EP group and 30 in IP group also received adjuvant radiotherapy.We compared the objective response rate(ORR) and safety of these 2 regimens,and analyzed the effects of radiotherapy and lymphocyte subset distribution on the survival outcomes of the patients.Results No significant difference was found between EP and IP groups in the ORR [67.7%(44/65) vs 57.0%(45/79),P=0.243],disease control rate [DCR,93.8%(61/65) vs 92.4%(73/79),P=0.328],median progression-free survival time [m PFS,5.05 vs 4.30 months,P=0.650],or medial overall survival time(m OS;13.95 vs 14.10 months,P=0.120).In both groups,the combination of chest radiotherapy significantly improved the m PFS and m OS of the patients as compared with chemotherapy alone.The patients with lowered counts of T4 and T8 lymphocyte subpopulations had significantly shorter m PFS and m OS than those with normal T4 and T8 cell counts.Compared with IP regimen,EP regimen was associated with a significantly lower incidence of diarrhea(7.7% vs 46.8%,P=0.020) but higher incidences of neutropenia(52.3% vs 22.8%,P=0.001) and anemia(73.8% vs 40.5%,P=0.013).Conclusion The therapeutic efficacy of EP and IP regimens is comparable for treatment of extensive-stage SCLC,and adjuvant radiotherapy can significantly improve the clinical outcomes of the patients.The patients with reduced counts of T4 and T8 lymphocyte subsets have poorer outcomes than those with normal counts.EP regimen is associated with high incidences of neutropenia and anemia,and IP regimen with a high incidence of diarrhea in the patients.
Objective To compare the efficacy and safety of etoposide plus platinum(EP) and irinotecan plus platinum(IP) regimens for treatment of extensive-stage small cell lung cancer(SCLC).Methods This retrospective study was conducted among 144 patients with extensive-stage SCLC receiving chemotherapy with EP regimen(65 cases) or IP regimen(79 cases) in our hospital during the period from2013 to 2017.Twenty-two patients in EP group and 30 in IP group also received adjuvant radiotherapy.We compared the objective response rate(ORR) and safety of these 2 regimens,and analyzed the effects of radiotherapy and lymphocyte subset distribution on the survival outcomes of the patients.Results No significant difference was found between EP and IP groups in the ORR [67.7%(44/65) vs 57.0%(45/79),P=0.243],disease control rate [DCR,93.8%(61/65) vs 92.4%(73/79),P=0.328],median progression-free survival time [m PFS,5.05 vs 4.30 months,P=0.650],or medial overall survival time(m OS;13.95 vs 14.10 months,P=0.120).In both groups,the combination of chest radiotherapy significantly improved the m PFS and m OS of the patients as compared with chemotherapy alone.The patients with lowered counts of T4 and T8 lymphocyte subpopulations had significantly shorter m PFS and m OS than those with normal T4 and T8 cell counts.Compared with IP regimen,EP regimen was associated with a significantly lower incidence of diarrhea(7.7% vs 46.8%,P=0.020) but higher incidences of neutropenia(52.3% vs 22.8%,P=0.001) and anemia(73.8% vs 40.5%,P=0.013).Conclusion The therapeutic efficacy of EP and IP regimens is comparable for treatment of extensive-stage SCLC,and adjuvant radiotherapy can significantly improve the clinical outcomes of the patients.The patients with reduced counts of T4 and T8 lymphocyte subsets have poorer outcomes than those with normal counts.EP regimen is associated with high incidences of neutropenia and anemia,and IP regimen with a high incidence of diarrhea in the patients.
引文
[1]VAN MEERBEECK J P,FENNELL D A,DE RUYSSCHERD K.Small-cell lung cancer[J].Lancet,2011,378(9804):1741-1755.DOI:10.1016/S0140-6736(11)60165-7.
[2]周小昀,李龙芸.小细胞肺癌的治疗进展与现状[J].癌症进展,2007,5(5):475-488.ZHOU X Y,LI L Y.Management of small cell lung caner[J].Oncol Prog,2007,5(5):475-488.
[3]HADDADIN S,PERRY M C.History of small-cell lung cancer[J].Clin Lung Cancer,2011,12(2):87-93.DOI:10.1016/j.cllc.2011.03.002.
[4]FRH M,DE RUYSSCHER D,POPAT S,et al.Small-cell lung cancer(SCLC):ESMO Clinical Practice Guidelines for Diagnosis,Treatment and Follow-up[J].Ann Oncol,2013,24(Suppl 6):vi99-105.DOI:10.1093/annonc/mdt178.
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[7]KIM D W,KIM H G,KIM J H,et al.Randomized phaseⅢtrial of irinotecan plus cisplatin versus etoposide plus cisplatin in chemotherapy-na6ve korean patients with extensive-disease small cell lung cancer[J].Cancer Res Treat,2018.DOI:10.4143/crt.2018.019.
[8]HANNA N,BUNN PA J R,LANGER C,et al.Randomized phaseⅢtrial comparing irinotecan/cisplatin with etoposide/cisplatin in patients with previously untreated extensive-stage disease small-cell lung cancer[J].J Clin Oncol,2006,24(13):2038-2043.DOI:10.1200/JCO.2005.04.8595.
[9]SHI Y,HU Y,HU X,et al.Cisplatin combined with irinotecan or etoposide for untreated extensive-stage small cell lung cancer:a multicenter randomized controlled clinical trial[J].Thoracic Cancer,2015,6(6):785-791.DOI:10.1111/1759-7714.12303.
[10]FISHER M D,D'ORAZIO A.Irinotecan and cisplatin versus eto-oside and cisplatin in small-cell lung cancer:JCOG9511[J].Clin Lung Cancer,2000,2(1):23-24.
[11]曾筱怡.IP和EP两种方案治疗广泛期小细胞癌疗效观察及安全性分析[J].当代医学,2016,22(10):151-152.DOI:10.3969 j,jssn.1099-4393.2016.10.23.ZENG X Y.Observation on the efficacy and safety of IP and EP in the treatment of extensive small cell cancer[J].Contemp Med,2016,22(10):151-152.DOI:10.3969 j,jssn.1099-4393.2016.10.23.
[12]LI-MING X,ZHAO L J,SIMONE C B 2ND,et al.Receipt of thoracic radiation therapy and radiotherapy dose are correlated with outcomes in a retrospective study of three hundred and six patients with extensive stage small-cell lung cancer[J].Radiother Oncol,2017,125(2):331-337.DOI:10.1016/j.radonc.2017.10.005.
[13]PATRICE G I,LESTER-COLL N H,YU J B,et al.Costeffectiveness of thoracic radiation therapy for extensive-stage small cell lung cancer using evidence from the chest radiotherapy extensive-stage small cell lung cancer trial(CREST)[J].Int J Radiat Oncol Biol Phys,2018,100(1):97-106.DOI:10.1016/j.ijrobp.2017.08.041.
[14]SLOTMAN B J,VAN TINTEREN H,PRAAG J O,et al.Use of thoracic radiotherapy for extensive stage small-cell lung cancer:a phase 3 randomised controlled trial[J].Lancet,2015,385(9962):36-42.DOI:10.1016/s0140-6736(14)61085-0.
[15]董丽华.外周血T细胞亚群在小细胞肺癌治疗中的应用价值[D].西宁:青海大学,2017.DONG L H.Value of peripheral blood T cell subsets in the treatment of small cell lung cancer[D].Xining:Qinghai U-niversity,2017.
[16]钱晓琴,林建潮,王社梁.T细胞亚群检测在恶性肿瘤患者辅助诊断中的价值研究[J].浙江实用医学,2016,21(3):170-171.QIAN X Q,LIN J C,WANG S L.Value of T cell subgroup detection in assisted diagnosis of malignant tumors[J].Zhejiang Prac Med,2016,21(3):170-171.
[2]周小昀,李龙芸.小细胞肺癌的治疗进展与现状[J].癌症进展,2007,5(5):475-488.ZHOU X Y,LI L Y.Management of small cell lung caner[J].Oncol Prog,2007,5(5):475-488.
[3]HADDADIN S,PERRY M C.History of small-cell lung cancer[J].Clin Lung Cancer,2011,12(2):87-93.DOI:10.1016/j.cllc.2011.03.002.
[4]FRH M,DE RUYSSCHER D,POPAT S,et al.Small-cell lung cancer(SCLC):ESMO Clinical Practice Guidelines for Diagnosis,Treatment and Follow-up[J].Ann Oncol,2013,24(Suppl 6):vi99-105.DOI:10.1093/annonc/mdt178.
[5]SANT M,ALLEMANI C,SANTAQUILANI M,et al.EURO-CARE-4.Survival of cancer patients diagnosed in 1995-1999.results and commentary[J].Eur J Cancer,2009,45(6):931-991.DOI:10.1016/j.ejca.2008.11.018.
[6]HAN D,WANG G,SUN L,et al.Comparison of irinotecan/platinum versus etoposide/platinum chemotherapy for extensive-stage small cell lung cancer:A meta-analysis[J].European J Cancer Care,2017,26(6):e12723.DOI:10.1111/ecc.12723.
[7]KIM D W,KIM H G,KIM J H,et al.Randomized phaseⅢtrial of irinotecan plus cisplatin versus etoposide plus cisplatin in chemotherapy-na6ve korean patients with extensive-disease small cell lung cancer[J].Cancer Res Treat,2018.DOI:10.4143/crt.2018.019.
[8]HANNA N,BUNN PA J R,LANGER C,et al.Randomized phaseⅢtrial comparing irinotecan/cisplatin with etoposide/cisplatin in patients with previously untreated extensive-stage disease small-cell lung cancer[J].J Clin Oncol,2006,24(13):2038-2043.DOI:10.1200/JCO.2005.04.8595.
[9]SHI Y,HU Y,HU X,et al.Cisplatin combined with irinotecan or etoposide for untreated extensive-stage small cell lung cancer:a multicenter randomized controlled clinical trial[J].Thoracic Cancer,2015,6(6):785-791.DOI:10.1111/1759-7714.12303.
[10]FISHER M D,D'ORAZIO A.Irinotecan and cisplatin versus eto-oside and cisplatin in small-cell lung cancer:JCOG9511[J].Clin Lung Cancer,2000,2(1):23-24.
[11]曾筱怡.IP和EP两种方案治疗广泛期小细胞癌疗效观察及安全性分析[J].当代医学,2016,22(10):151-152.DOI:10.3969 j,jssn.1099-4393.2016.10.23.ZENG X Y.Observation on the efficacy and safety of IP and EP in the treatment of extensive small cell cancer[J].Contemp Med,2016,22(10):151-152.DOI:10.3969 j,jssn.1099-4393.2016.10.23.
[12]LI-MING X,ZHAO L J,SIMONE C B 2ND,et al.Receipt of thoracic radiation therapy and radiotherapy dose are correlated with outcomes in a retrospective study of three hundred and six patients with extensive stage small-cell lung cancer[J].Radiother Oncol,2017,125(2):331-337.DOI:10.1016/j.radonc.2017.10.005.
[13]PATRICE G I,LESTER-COLL N H,YU J B,et al.Costeffectiveness of thoracic radiation therapy for extensive-stage small cell lung cancer using evidence from the chest radiotherapy extensive-stage small cell lung cancer trial(CREST)[J].Int J Radiat Oncol Biol Phys,2018,100(1):97-106.DOI:10.1016/j.ijrobp.2017.08.041.
[14]SLOTMAN B J,VAN TINTEREN H,PRAAG J O,et al.Use of thoracic radiotherapy for extensive stage small-cell lung cancer:a phase 3 randomised controlled trial[J].Lancet,2015,385(9962):36-42.DOI:10.1016/s0140-6736(14)61085-0.
[15]董丽华.外周血T细胞亚群在小细胞肺癌治疗中的应用价值[D].西宁:青海大学,2017.DONG L H.Value of peripheral blood T cell subsets in the treatment of small cell lung cancer[D].Xining:Qinghai U-niversity,2017.
[16]钱晓琴,林建潮,王社梁.T细胞亚群检测在恶性肿瘤患者辅助诊断中的价值研究[J].浙江实用医学,2016,21(3):170-171.QIAN X Q,LIN J C,WANG S L.Value of T cell subgroup detection in assisted diagnosis of malignant tumors[J].Zhejiang Prac Med,2016,21(3):170-171.