吉西他滨固定剂量率或标准输注联合奥沙利铂方案治疗进展期胆管癌随机对照研究

  目的  探讨奥沙利铂分别与吉西他滨固定剂量率输注、常规输注联合方案对进展期胆管癌化疗疗效、不良反应及其对患者生存时间的影响。  方法  2010年1月至2012年12月南京医科大学附属淮安第一医院病理确诊的93例初治、无手术指征进展期胆管癌和术后复发或转移性胆管癌患者，随机分为研究组（47例）和对照组（46例）。研究组采用吉西他滨固定剂量率即10 mg/（m2·min）输注联合奥沙利铂；对照组采用吉西他滨标准输注（30 min）联合奥沙利铂方案化疗，每21 d重复，每例患者完成至少2个周期化疗，并进行随访。治疗结束后对2组疗效、不良反应进行评价。  结果  治疗前2组患者临床特征具有均衡性（P > 0.05）。客观缓解率、临床获益率研究组高于对照组，差异均有统计学意义（P < 0.05）；研究组的生存时间OS、肿瘤进展时间TTP较对照组明显延长，差异均有统计学意义（P < 0.05）。不良反应主要为血液学毒性，尤其Ⅲ~Ⅳ度白细胞、血小板减少发生率研究组明显高于对照组（P < 0.05）；而非血液学不良反应发生率2组相近（P > 0.05）。  结论  以吉西他滨固定剂量率输注联合奥沙利铂方案治疗进展期胆管癌，方法可行，具有较高的客观缓解效率，延长了OS及TTP；非血液学不良反应发生率较低，患者耐受性较好；但其血液学毒性较为显著，需引起足够重视，值得进一步研究其临床应用价值。 

Random and control study comparing gemcitabine administered in fixed dose rate with a more standard infusion combined with oxaliplatin regimens in advanced biliary tract cancer patients

  Objective  To investigate and compare the effects of oxaliplatin combined with gemcitabine administered in a fixed dose rate and that administered in a more standard infusion in advanced biliary tract cancer patients on chemotherapeutic efficacy, toxicities, and survival time.  Methods  A total of 93 cancer patients were recruited from February 1, 2010 to December 12, 2012 in the First Hospital of Huai'an City Affiliated Nanjing Medical College. Those recruited were either newly diagnosed unresectable advanced biliary tract cancer patients by percutaneous liver biopsy or relapse or metastatic biliary tract cancer patients after operation. The patients were randomly divided into two groups. The first group was the study group in which the patients received chemotherapy with gemcitabine in a fixed dose rate of 10 mg/m2 per minute combined with oxaliplatin regimens. The other group was the control group in which the patients received chemotherapy with gemcitabine in a more standardized infusion within 30 min combined with oxaliplatin regimens. Each patient received four cycles, with at least two cycles of chemotherapy with GEMOX regimens every 21 d, with follow-up until death. The chemotherapeutic efficacy was evaluated. Toxicities were documented after each cycle.  Results  The clinical characteristics of the two groups were well balanced before chemotherapy (P > 0.05). The response rate (RR) and clinical benefit response of the study group were higher than those of the control group (P < 0.05). The overall survival (OS) and time to progress (TTP) of the study group were longer than those of the control group (P < 0.05). With respect to adverse events, the major side effect was hematological toxicity. The rate of grade Ⅲ/Ⅳ leucocytopenia and thrombocytopenia in the study group was remarkably higher than that in the control group (P < 0.05). However, the rate of non-hematological toxicity was similar (P > 0.05).  Conclusion  Gemcitabine in a fixed dose rate combined with oxaliplatin regimens is a feasible and effective scheme in treating advanced biliary tract cancer patients. RR is higher and OS and TTP are longer under this scheme. Non-hematological toxicities are also well tolerated. However, hematological toxicity is distinguished. These results guide us to be prudent in utilizing this regimen. The investigation of the value of gemcitabine in a fixed dose rate combined with oxaliplatin in treating advanced biliary tract cancer patients is worth pursuing in future clinical trials.