IP方案与CAO方案二线治疗复发小细胞肺癌的疗效及毒副作用比较研究
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摘要
目的:分析IP(伊立替康联合奈达铂)及CAO(环磷酰胺、表柔比星、长春瑞滨)方案在二线治疗中的疗效及安全性,旨在为临床选择二线治疗方案提供潜在可能。方法:回顾性分析二线治疗使用IP或CAO方案化疗的小细胞肺癌患者56例,评估两种方案的疗效及安全性。结果:入组的56例患者中46例患者可评价近期疗效,IP组客观缓解率为24.1%,CAO组为23.5%(P=1.000),IP组疾病控制率为58.6%,CAO组为29.4%(P=0.056);IP组中位PFS(无进展生存期)为3.0个月,CAO组中位PFS为2.6个月,两组中位OS(总生存期)分别为6.8个月和7.1个月,均无统计学差异。对生存时间进行Cox分析显示接受二线治疗前PS评分(P=0.032)、二线治疗前接受胸部放疗(P=0.034)是接受二线治疗总生存时间的独立预后因素。对两组的安全性分析显示IP组的腹泻发生率高于CAO组(P=0.034)。结论:在复发小细胞肺癌二线治疗中,IP方案与CAO方案效果相当,IP方案腹泻发生率较高。
Objective: To evaluate the efficacy and safety of IP(irinotecan plus nedaplatin) and CAO(cyclophosphamide combined with epirubicin and vinorelbine) in the second-line treatment of small cell lung cancer. Methods: This study retrospectively analyzed 56 patients who were diagnosed with small cell lung cancer. All patients were treated with IP or CAO as second-line regimes. The efficacy and the safety of the two groups were evaluated. Results: Of the 56 patients, 46 patients were eligible to evaluate the short-term efficacy. In the IP group and CAO group, the ORR were 24.1% and 23.5%, and the DCR were 58.6% and 29.4%, respectively. There was no statistically significant difference(P =1.000;P =0.056). The median PFS were 3.0 months in the IP group and 2.6 months in the CAO group. The median OS was 6.8 months and 7.1 months, respectively. No significant difference was observed between the two groups. Multivariate Cox analysis showed that the thoracic radiotherapy(P =0.034) and ECOG PS(P =0.032) were independent prognostic factors. In the assessment of toxicity, the diarrhea incidence was higher in IP group(P =0.034). Conclusion: In the second-line treatment of recurrent small cell lung cancer, IP regimen does not show superiority to CAO regimen, but the incidence of diarrhea of IP regimen is higher.
Objective: To evaluate the efficacy and safety of IP(irinotecan plus nedaplatin) and CAO(cyclophosphamide combined with epirubicin and vinorelbine) in the second-line treatment of small cell lung cancer. Methods: This study retrospectively analyzed 56 patients who were diagnosed with small cell lung cancer. All patients were treated with IP or CAO as second-line regimes. The efficacy and the safety of the two groups were evaluated. Results: Of the 56 patients, 46 patients were eligible to evaluate the short-term efficacy. In the IP group and CAO group, the ORR were 24.1% and 23.5%, and the DCR were 58.6% and 29.4%, respectively. There was no statistically significant difference(P =1.000;P =0.056). The median PFS were 3.0 months in the IP group and 2.6 months in the CAO group. The median OS was 6.8 months and 7.1 months, respectively. No significant difference was observed between the two groups. Multivariate Cox analysis showed that the thoracic radiotherapy(P =0.034) and ECOG PS(P =0.032) were independent prognostic factors. In the assessment of toxicity, the diarrhea incidence was higher in IP group(P =0.034). Conclusion: In the second-line treatment of recurrent small cell lung cancer, IP regimen does not show superiority to CAO regimen, but the incidence of diarrhea of IP regimen is higher.
引文
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[24]Pijls-Johannesma M C,De Ruysscher D,Lambin P,et al.Early versus late chest radiotherapy for limited stage small cell lung cancer[J].Cochrane Database Syst Rev,2005,4(1):Cd004700
[25]De Ruysscher D,Pijls-Johannesma M,Bentzen S M,et al.Time between the first day of chemotherapy and the last day of chest radiation is the most important predictor of survival in limited-disease small-cell lung cancer[J].J Clin Oncol,2006,24(7):1057
[26]Zhou M,Wang Z,Yao Y,et al.Neuron-specific enolase and response to initial therapy are important prognostic factors in patients with small cell lung cancer[J].Clin Translat Oncol,2017,19(7):865
[2]Rodriguez E,Lilenbaum R C.Small cell lung cancer:past,present,and future[J].Curr Oncol Rep,2010,12(5):327
[3]Noda K,Nishiwaki Y,Kawahara M,et al.Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small-cell lung cancer[J].N Engl J Med,2002,346(2):85
[4]Jiang J W,Liang X H,Zhou X L,et al.A Meta-Analysis of randomized controlled trials comparing irinotecan/Platinum with etoposide/Platinum in patients with previously untreated Extensive-Stage small cell lung cancer[J].J Thorac Oncol,2010,5(6):867
[5]Lima J P,Dos Santos L V,Sasse E C,et al.Camptothecins compared with etoposide in combination with Platinum analog in extensive stage small cell lung cancer:systematic review with meta-analysis[J].J Thorac Oncol,2010,5(12):1986
[6]Asai N,Ohkuni Y,Kaneko N,et al.Relapsed small cell lung cancer:treatment options and latest developments[J].Ther Adv Med Oncol,2014,6(2):69
[7]Kanzawa F,Koizumi F,Koh Y,et al.In vitro synergistic interactions between the cisplatin analogue nedaplatin and the DNA topoisomerase I inhibitor irinotecan and the mechanism of this interaction[J].Clin Cancer Res,2001,7(1):202
[8]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].Eur J Cancer Care(Engl),2017,26(6,SI):115
[9]Ohe M,Oshita F,Kenmotsu Y,et al.Nedaplatin and irinotecan for patients with recurrent small cell lung cancer[J].J Exp Ther Oncol,2012,10(1):65
[10]Sevinc A,Kalender M E,Altinbas M,et al.Irinotecan as a secondline monotherapy for small cell lung cancer[J].Asian Pac J Cancer Prev,2011,12(4):1055
[11]Zhang M Q,Lin X,Li Y,et al.Irinotecan as a second-line chemotherapy for small cell lung cancer:a systemic analysis[J].Asian Pac J Cancer Prev,2015,16(5):1993
[12]Hagmann R,Hess V,Zippelius A,et al.Second-Line therapy of Small-Cell lung cancer:topotecan compared to a combination treatment with adriamycin,cyclophosphamide and vincristine(ACO)-a single center experience[J].J Cancer,2015,6(11):1148
[13]Shepherd F A,Evans W K,Maccormick R,et al.Cyclophosphamide,doxorubicin,and vincristine in etoposide-and cisplatin-resistant small cell lung cancer[J].Cancer Treat Rep,1987,71(10):941
[14]Sculier J P,Klastersky J,Libert P,et al.Cyclophosphamide,doxorubicin and vincristine with amphotericin B in sonicated liposomes as salvage therapy for small cell lung cancer[J].Eur J Cancer,1990,26(8):919
[15]Von Pawel J,Schiller J H,Shepherd F A,et al.Topotecan versus cyclophosphamide,doxorubicin,and vincristine for the treatment of recurrent small-cell lung cancer[J].J Clin Oncol,1999,17(2):658
[16]Oronsky B,Caroen S,Zeman K,et al.A partial response to reintroduced chemotherapy in a resistant small cell lung cancer patient after priming with RRx-001[J].Clin Med Insights Oncol,2016,10:105
[17]Morise M,Niho S,Umemura S,et al.Low-dose irinotecan as a second-line chemotherapy for recurrent small cell lung cancer[J].Jpn J Clin Oncol,2014,44(9):846
[18]Goto K,Ohe Y,Shibata T,et al.Combined chemotherapy with cisplatin,etoposide,and irinotecan versus topotecan alone as secondline treatment for patients with sensitive relapsed small-cell lung cancer(JCOG0605):a multicentre,open-label,randomised phase 3trial[J].Lancet Oncol,2016,17(8):1147
[19]Sundstrom S,Bremnes R M,Kaasa S,et al.Second-line chemotherapy in recurrent small cell lung cancer.Results from a crossover schedule after primary treatment with cisplatin and etoposide(EPregimen)or cyclophosphamide,epirubicin,and vincristin(CEV-regimen)[J].Lung Cancer,2005,48(2):251
[20]Minami S,Ogata Y,Ihara S,et al.Retrospective analysis of outcomes and prognostic factors of chemotherapy for small-cell lung cancer[J].Lung Cancer(Auckland,NZ),2016,7:35
[21]Fried D B,Morris D E,Poole C,et al.Systematic review evaluating the timing of thoracic radiation therapy in combined modality therapy for limited-stage small-cell lung cancer[J].J Clin Oncol,2004,22(23):4837
[22]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(London,England),2015,385(9962):36
[23]Auperin A,Arriagada R,Pignon J P,et al.Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission.Prophylactic Cranial Irradiation Overview Collaborative Group[J].N Engl J Med,1999,341(7):476
[24]Pijls-Johannesma M C,De Ruysscher D,Lambin P,et al.Early versus late chest radiotherapy for limited stage small cell lung cancer[J].Cochrane Database Syst Rev,2005,4(1):Cd004700
[25]De Ruysscher D,Pijls-Johannesma M,Bentzen S M,et al.Time between the first day of chemotherapy and the last day of chest radiation is the most important predictor of survival in limited-disease small-cell lung cancer[J].J Clin Oncol,2006,24(7):1057
[26]Zhou M,Wang Z,Yao Y,et al.Neuron-specific enolase and response to initial therapy are important prognostic factors in patients with small cell lung cancer[J].Clin Translat Oncol,2017,19(7):865