Doherty Mark K, McNamara Mairéad G, Aneja Priya, McInerney Emma, Moignard Stephanie, Horgan Anne M, Jiang Haiyan, Panzarella Tony, Jang Raymond, Dhani Neesha, Hedley David, Knox Jennifer J
Department of Medical Oncology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
Department of Medical Oncology, The Christie NHS Foundation Trust and Division of Molecular & Clinical Cancer Sciences, University of Manchester, Manchester, UK.
J Gastrointest Oncol. 2017 Apr;8(2):352-360. doi: 10.21037/jgo.2017.03.06.
Patients with advanced biliary tract cancer (BTC) are often treated with palliative chemotherapy (PC). Standard PC since 2010 is a cisplatin/gemcitabine doublet, with median overall survival (OS) of 11.7 months from the ABC-02 trial. Prior to this, our institutional standard was gemcitabine and fluoropyrimidine. The ABC-02 study used 8 cycles of PC as standard with treatment stopped even in the absence of disease progression, but some patients may benefit from continuing PC longer than 8 cycles.
Patients treated with at least 2 cycles of PC for advanced BTC in Princess Margaret Cancer Centre between 1987 and 2015 were included, and divided into 2 groups for analysis-long-term responders (LTR) who received 9 or more cycles, and controls (2-8 cycles). Data was collected on demographics, clinicopathological features, PC regimen, toxicities, and survival. The primary outcome measure was OS, with secondary analyses including progression-free survival (PFS) and toxicity rates between groups.
A total of 382 patients were identified, 123 who met the criteria for LTR and 259 who were included as controls. The baseline demographic and clinical characteristics were similar, although more patients in the control group had gallbladder cancer or extrahepatic cholangiocarcinoma than LTR (P=0.024), and more patients in the LTR group were treated with combination chemotherapy regimens (93% 82% in controls, P=0.003). The LTR patients had significantly longer PFS (median 13.3 4.1 months, P<0.001) and longer OS than controls (median 22.1 9.2 months, P<0.001). In LTR patients, 15% had a break from chemotherapy of 3 months or more and restarted the same regimen. The LTR patients reported higher rates of nausea, cutaneous and hematologic toxicity, but also more frequently went on to receive second-line chemotherapy (47% 33%, P=0.007). In multivariable analysis of OS, LTR, good performance status and intrahepatic site of cancer were associated with better survival.
From this institutional dataset, a significant proportion of patients continued chemotherapy past 8 cycles, and appeared to derive benefit from longer duration of treatment. Toxicity rates were higher in this group, but manageable as evidenced by second-line treatment rates. Discontinuation of chemotherapy for reasons other than toxicity or progression may result in loss of disease control and impact survival in this population; these data suggest the use of continued chemotherapy to disease progression in patients with advanced BTC is a favorable option.
晚期胆管癌（BTC）患者常接受姑息化疗（PC）。自2010年以来，标准的PC方案是顺铂/吉西他滨双联疗法，根据ABC - 02试验，中位总生存期（OS）为11.7个月。在此之前，我们机构的标准方案是吉西他滨和氟嘧啶。ABC - 02研究将8周期的PC作为标准方案，即使在没有疾病进展的情况下也会停止治疗，但一些患者可能从超过8周期的持续PC治疗中获益。
纳入1987年至2015年在玛格丽特公主癌症中心接受至少2周期PC治疗的晚期BTC患者，并分为两组进行分析——接受9个或更多周期治疗的长期缓解者（LTR）和对照组（2 - 8周期）。收集了患者的人口统计学、临床病理特征、PC方案、毒性反应和生存情况等数据。主要结局指标是OS，次要分析包括无进展生存期（PFS）和两组之间的毒性发生率。
共确定了382例患者，其中123例符合LTR标准，259例作为对照组。两组患者的基线人口统计学和临床特征相似，尽管对照组中胆囊癌或肝外胆管癌患者比LTR组更多（P = 0.024），且LTR组中接受联合化疗方案治疗的患者更多（93%对对照组的82%，P = 0.003）。LTR患者的PFS明显更长（中位13.3对4.1个月，P < 0.001），OS也比对照组更长（中位22.1对9.2个月，P < 0.001）。在LTR患者中，15%的患者化疗中断3个月或更长时间后重新开始相同方案。LTR患者报告的恶心、皮肤和血液学毒性发生率更高，但接受二线化疗的频率也更高（47%对33%，P = 0.007）。在OS的多变量分析中，LTR、良好的身体状况和肝内癌灶与更好的生存相关。
从这个机构数据集来看，相当比例的患者化疗超过8周期，且似乎从更长疗程的治疗中获益。该组的毒性发生率更高，但二线治疗率表明毒性是可控的。因毒性或疾病进展以外的原因停止化疗可能导致疾病控制丧失并影响该人群的生存；这些数据表明，对于晚期BTC患者，持续化疗至疾病进展是一个有利的选择。
