培美曲塞联合长春瑞滨治疗一线化疗失败的复发转移性宫颈癌的疗效研究

doi:10.12114/j.issn.1007-9572.2019.00.393

摘要/Abstract

摘要： 背景　复发转移性宫颈癌一线化疗后，疾病进展（PD）或控制不佳时尚无标准化疗方案，单药培美曲塞和单药长春瑞滨化疗的研究已有报道，但两药联合化疗的临床疗效研究鲜见报道。目的　分析培美曲塞联合长春瑞滨治疗一线化疗失败的复发转移性宫颈癌的近期疗效及不良反应。方法　回顾性分析2014年1月—2017年12月贵州省人民医院收治的29例一线化疗失败的复发转移性宫颈癌患者的临床资料。患者使用培美曲塞联合长春瑞滨进行治疗，21 d为1个周期，行4~6个周期治疗，评价近期疗效及毒副作用发生情况。结果　29例宫颈癌患者均至少完成4个周期的化疗，无完全缓解（CR）患者，部分缓解（PR）6例（20.7%）、疾病稳定（SD）9例（31.0%）、PD 14例（48.3%），有效率为20.7%（6/29），疾病控制率为51.7%（15/29）。中位无疾病进展生存（PFS）时间为6.5个月（2.6~13.7个月），中位总生存（OS）时间为10.2个月（2.6~30.1个月）。宫颈鳞癌、腺癌患者行培美曲塞联合长春瑞滨的疗效比较〔PR分别为5、1例，SD分别为8、1例，PD分别为11、3例〕，盆腔内、外有转移病灶患者行培美曲塞联合长春瑞滨的疗效比较〔PR分别为6、0例，SD分别为7、2例，PD分别为11、3例〕，差异均无统计学意义（u=0.438、0.908，P=0.661、0.364）。29例患者均有不同程度的毒副作用，较重的（3~4级）毒副作用多为白细胞计数减少、中性粒细胞计数减少、血小板计数减少，其次是恶心呕吐、贫血、天冬氨酸氨基转移酶升高；经对应治疗，均能按周期完成化疗。结论　培美曲塞联合长春瑞滨方案治疗复发转移性宫颈癌患者近期疗效较好，其毒副作用患者可耐受，远期疗效有待进一步研究。

关键词: 培美曲塞；长春瑞滨；放化疗, 辅助；宫颈肿瘤；治疗结果；毒副作用

Abstract: Background　 There are no standardized regimens for recurrent and metastatic cervical cancer patients with disease progression or poor controlled conditions after first-line chemotherapy.Although use of pemetrexed or vinorelbine chemotherapy for such patients has been reported，the clinical efficacy of combination of these two drugs is rarely reported.Objective　To analyze the short-term efficacy and side effects of pemetrexed combined with vinorelbine in the treatment of recurrent and metastatic cervical cancer after failure of first-line chemotherapy.Methods　A retrospective analysis was conducted on 29 cases of recurrent and metastatic cervical cancer after failure of first-line chemotherapy recruited from Guizhou Provincial People's Hospital from January 2014 to December 2017.All of them were treated with pemetrexed plus vinorelbine for 4-6 cycles of treatment（a cycle duration was defined as 21days）．Short-term efficacy and toxic side effects were evaluated.Results　All the cases completed at least 4 cycles of chemotherapy.The rates of complete remission（CR），partial remission（PR），stable disease（SD），progressive disease（PD） were 0，20.7%（6/29），31.0%（9/29），48.3%（14/29），20.7%（6/29），respectively，indicating that a disease control rate of 51.7%（15/29） was achieved.The median progression-free survival（PFS） was 6.5 months（range：2.6-13.7） and the median total survival（OS） was 10.2 months（range：2.6-30.1）．Cervical squamous cell carcinoma and cervical adenocarcinoma patients showed similar overall response rates：PR〔0.8%（5/24） vs 20%（1/5）〕，SD〔33.3%（8/24） vs 20%（1/5）〕 and PD〔45.8%（11/24） vs 60%（3/5）〕（u=0.438，P=0.661）．Moreover，those with cervical cancer spreading to or growing into the walls of the pelvis and those with cervical cancer growing out of the pelvis also showed similar overall response rates：PR〔25.0%（6/24） vs 0〕，SD〔29.1%（7/24） vs 40%（2/5）〕and PD〔45.8%（11/24） vs 60%（3/5）〕（u=0.908，P=0.364）．All the cases demonstrated different degrees of toxic side effects，the most serious（grade 3-4） were leukopenia，neutropenia and thrombocytopenia，followed by nausea and vomiting，anemia，and elevated aspartate aminotransferase，but after corresponding treatment，all of them completed the chemotherapy.Conclusion　Pemetrexed combined with vinorelbine has a good short-term efficacy in the treatment of recurrent and metastatic cervical cancer，with tolerable toxic side effects.But its.long-term efficacy needs to be further studied.

Key words: Pemetrexed；Vinorelbine；Chemoradiotherapy, adjuvant；Uterine cervical neoplasms；Treatment outcome；Tolerable toxic side effects

鲁亮,刘爱华,张汉群,等. 培美曲塞联合长春瑞滨治疗一线化疗失败的复发转移性宫颈癌的疗效研究[J]. 中国全科医学, 2019, 22(30): 3679-3682. DOI: 10.12114/j.issn.1007-9572.2019.00.393.
LU Liang,LIU Aihua,ZHANG Hanqun, et al. Efficacy of Pemetrexed with Vinorelbine in Recurrent and Metastatic Cervical Cancer after Failure of First-line Chemotherapy　[J]. Chinese General Practice, 2019, 22(30): 3679-3682. DOI: 10.12114/j.issn.1007-9572.2019.00.393.

参考文献

［1］PARK C K，OH I J，KIM K S，et al．Randomized phase Ⅲ study of docetaxel plus cisplatin versus pemetrexed plus cisplatin as first-line treatment of nonsquamous non-small-cell lung cancer：a TRAIL trial［J］．Clin Lung Cancer，2017，18（4）：e289-296．DOI：10.1016/j.cllc.2017.01.002.
［2］LESTER J F，CASBARD A C，AL-TAEI S，et al．A single centre phaseⅡtrial to assess the immunological activity of TroVax? plus pemetrexed/cisplatin in patients with malignant pleural mesothelioma - the SKOPOS trial［J］．Oncoimmunology，2018，7（12）：e1457597．DOI：10.1080/2162402X.2018.1457597.
［3］GOEDHALS L，VAN WIYK A L，SMITH B L，et al．Pemetrexed（Alimta，LY231514） demonstrates clinical activity in chemonaive patients with cervical cancer in a phase Ⅱ single-agent trial［J］．Int J Gynecol Cancer，2006，16（3）：1172-1178．DOI：10.1111/j.1525-1438.2006.00451.x.
［4］EICHENAUER D A，ALEMAN B M P，ANDRé M，et al．Hodgkin lymphoma：ESMO Clinical Practice Guidelines for diagnosis，treatment and follow-up［J］．Ann Oncol，2018，29（Suppl 4）：iv19-29．DOI：10.1093/annonc/mdy080.
［5］YANG Z J，CHEN D D，ZHANG J Q，et al．The efficacy and safety of neoadjuvant chemotherapy in the treatment of locally advanced cervical cancer：a randomized multicenter study［J］．Gynecol Oncol，2016，141（2）：231-239．DOI：10.1016/j.ygyno.2015.06.027.
［6］TSUCHIDA Y，THERASSE P.Response evaluation criteria in solid tumors（RECIST）：new guidelines［J］．Med Pediatr Oncol，2001，37（1）：1-3．DOI：10.1002/mpo.1154.
［7］ZHANG S，LIANG F，TANNOCK I.Use and misuse of common terminology criteria for adverse events in cancer clinical trials［J］．BMC Cancer，2016，16（4）：392．DOI：10.1186/s12885-016-2408-9.
［8］TEWARI K S，SILL M W，PENSON R T，et al．Bevacizumab for advanced cervical cancer：final overall survival and adverse event analysis of a randomised，controlled，open-label，phase 3 trial（Gynecologic Oncology Group 240）［J］．Lancet，2017，390（10103）：1654-1663．DOI：10.1016/S0140-6736（17）31607-0.
［9］MOORE D H，BLESSING J A，MCQUELLON R P，et al．Phase III study of cisplatin with or without paclitaxel in stage ⅣB，recurrent，or persistent squamous cell carcinoma of the cervix：a gynecologic oncology group study［J］．JCO，2004，22（15）：3113-3119．DOI：10.1200/jco.2004.04.170.
［10］LONG H J III，BUNDY B N，GRENDYS E C Jr，et al．Randomized phase III trial of cisplatin with or without topotecan in carcinoma of the uterine cervix：a gynecologic oncology group study［J］．JCO，2005，23（21）：4626-4633．DOI：10.1200/jco.2005.10.021.
［11］BOARDMAN C H，BRADY W E，DIZON D S，et al．A phase Ⅰ evaluation of extended field radiation therapy with concomitant cisplatin chemotherapy followed by paclitaxel and carboplatin chemotherapy in women with cervical carcinoma metastatic to the para-aortic lymph nodes：an NRG Oncology/Gynecologic oncology group study［J］．Gynecol Oncol，2018，151（2）：202-207．DOI：10.1016/j.ygyno.2018.08.006.
［12］ROSEN V M，GUERRA I，MCCORMACK M，et al．Systematic review and network meta-analysis of bevacizumab plus first-line topotecan-paclitaxel or cisplatin-paclitaxel versus non-bevacizumab-containing therapies in persistent，recurrent，or metastatic cervical cancer［J］．Int J Gynecol Cancer，2017，27（6）：1237-1246．DOI：10.1097/igc.0000000000001000.
［13］TEWARI K S，SILL M W，LONG H J 3rd，et al．Improved survival with bevacizumab in advanced cervical cancer［J］．N Engl J Med，2014，370（8）：734-743．DOI：10.1056/NEJMoa1309748.
［14］KITAGAWA R，KATSUMATA N，SHIBATA T，et al．Paclitaxel plus carboplatin versus paclitaxel plus cisplatin in metastatic or recurrent cervical cancer：the open-label randomized phase Ⅲ trial JCOG0505［J］．J Clin Oncol，2015，33（19）：2129-2135．DOI：10.1200/JCO.2014.58.4391.
［15］MILLER D S，BLESSING J A，BODURKA D C，et al．Evaluation of pemetrexed（Alimta，LY231514） as second line chemotherapy in persistent or recurrent carcinoma of the cervix：a phase Ⅱ study of the Gynecologic Oncology Group［J］．Gynecol Oncol，2008，110（1）：65-70．DOI：10.1016/j.ygyno.2008.03.009.
［16］GOEDHALS L，VAN WIYK A L，SMITH B L，et al．Pemetrexed（Alimta，LY231514） demonstrates clinical activity in chemonaive patients with cervical cancer in a phase Ⅱ single-agent trial［J］．Int J Gynecol Cancer，2006，16（3）：1172-1178．DOI：10.1111/j.1525-1438.2006.00451.x.
［17］MUGGIA F M，BLESSING J A，METHOD M，et al．Evaluation of vinorelbine in persistent or recurrent squamous cell carcinoma of the cervix：a Gynecologic Oncology Group study［J］．Gynecol Oncol，2004，92（2）：639-643．DOI：10.1016/j.ygyno.2003.10.045.
［18］MORRIS M，BRADER K R，LEVENBACK C，et al．Phase Ⅱ study of vinorelbine in advanced and recurrent squamous cell carcinoma of the cervix［J］．J Clin Oncol，1998，16（3）：1094-1098．DOI：10.1200/JCO.1998.16.3.1094.