ASCO 2013：S-1联合吉西他滨可用于胰腺癌术后化疗

　　日本学者的一项研究显示，S-1和吉西他滨（GS）作为胰腺癌患者术后辅助化疗药物，显示出和GEM相似的有效性。根据该结果，S-1联合GS辅助化疗对于胰腺癌（PC）患者术后有效。 

　　目前，虽然对于PC手术后患者使用GEM辅助化疗已经作为标准方案，但预后依然欠佳。最近的研究显示S-1的非劣效性，GS对于GEM的优势在于延长不能进行手术切除的胰腺癌患者的无进展生存期。该研究纳入经历过根治性手术带有侵入性导管且之前没有接受放化疗的PC患者。通过R0/1、分期和研究机构分层后，患者被随机分为三个组，在术后8周内分别接受GEM (第1、8和15天静脉滴注GEM 1g/ m^2,，每周4次，持续12周)、S-1 (第1-14天根据体表面积每天口服80/100/120mg，每周3次，持续16周)和GS(第1-14天根据体表面积每天口服S-1 60/80/100mg，第8和15天静脉滴注GEM 1g/ m^2, ，每周三次，持续16周) 治疗。研究主要终点是2年无病生存率(DFS) ，次要终点是总体生存率(OS)和安全性。

　　结果显示，在2007年1月到2010年10月期间，96例患者被随机分配到三个治疗组(每组32 人)，各组患者(GEM/S-1/GS)临床特征相似，年龄相仿，(分别为66、67和66岁), 肿瘤位置(头部分别为66%、69%和75%)、肿瘤状态(T3+4分别为88%、78%和91%)、淋巴结状态(阳性分别为75%、69%和75%)。直到2012年11月，74例(77%) 患者保持无病生存。GEM组、S-1组和GS组的两年DFS分别为24.2%、28.1%和34.4%，各组之间无显著差异。三组患者的平均OS分别为21个月、26个月和27.9个月。三组患者的3/4级毒性反应是 血液学改变分别为63%、10%和74% ，非血液学改变分别为17%、10%和23%。在研究中没有发现治疗相关的死亡。

A randomized phase II trial of adjuvant chemotherapy with S-1 versus S-1 and gemcitabine (GS) versus gemcitabine alone (GEM) in patients with resected pancreatic cancer (CAP-002 study)
Background
Although the adjuvant therapy using GEM is now the standard therapy for patients with resected pancreatic cancer (PC), the prognosis still remains poor. Resent study demonstrated the non-inferiority of S-1 and superiority of GS to GEM with respect to progression free survival in patients with unresectable pancreatic cancer.
Methods
Patients with invasive ductal PC who underwent radical surgery were enrolled. After stratification for R0/1, stage and institution, patients were randomized to receive GEM (GEM 1g/ m2, iv, d1, 8, and 15, q4w X12), S-1 (80/100/120mg/day based on BSA, po, d1-14, q3w X 16) or GS (S-1 60/80/100mg/day based on BSA po, d1-14 plus GEM 1g/ m2, iv, d8, 15, q3w X 16) within 8weeks after operation. Eligibility included histological residual tumor (R) 0 or 1, and no previous chemo- or/and radiation therapy. Primary endpoint was 2y disease free survival (DFS) rate and secondary endpoints included overall survival (OS), and safety.
Results
Between January 2007 and October 2010, 96 patients were randomized into the three arms of the trial (32 pts to each group). Patients’ characteristics were well balanced (GEM/S-1/GS) with regard to age (66/67/66y), tumor location (head 66/69/75%), tumor status (T3+4 88/78/91%), and nodal status (positive 75/69/75%). Until November 2012, 74 events (77%) have occurred for DFS. Two year DFS rate was 24.2%, 28.1% and 34.4% in GEM, S-1 and GS, respectively and there was no significant difference between groups. The median OS was 21m in GEM, 26m in S-1 and 27.9m in GS (Log rank test: N.S.). Grade 3/4 toxicities in GEM/S-1/GS were hematological 63/10/74% and non-hematological 17/10/23%, respectively. No treatment related death was observed during the study.
Conclusions
S-1 and GS provided similar efficacy to GEM as the adjuvant chemotherapy for resected PC. According to the results, S-1 and GS is the adequate combination for phase III trial to examine the efficacy of adjuvant chemotherapy for PC. Clinical trial information: UMIN000002000.