Morizane Chigusa, Okusaka Takuji, Furuse Junji, Ishii Hiroshi, Ueno Hideki, Ikeda Masafumi, Nakachi Kohei, Najima Mina, Ogura Takashi, Suzuki Eiichiro
Division of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
Cancer Chemother Pharmacol. 2009 Jan;63(2):313-9. doi: 10.1007/s00280-008-0741-7. Epub 2008 Apr 9.
Gemcitabine monotherapy or gemcitabine-containing combination chemotherapy is the standard first-line therapy for advanced pancreatic cancer. After disease progression, there is no standard regimen available. In a previous phase II trial, S-1 has been reported to show considerable efficacy, achieving a response rate of 37.5% in chemo-naïve patients with pancreatic cancer. This study evaluated the efficacy and toxicity of S-1 in patients with gemcitabine-refractory metastatic pancreatic cancer.
Eligibility criteria were histologically proven pancreatic adenocarcinoma with confirmation of progressive disease while receiving gemcitabine-based first-line chemotherapy, 20-74 years of age, Karnofsky performance status of 80-100 points, with measurable metastatic lesions, adequate hematological, renal and liver functions, and written informed consent. S-1 was administered orally at 40 mg/m(2) twice daily for 28 days with a rest period of 14 days as one course. Administration was repeated until the appearance of disease progression or unacceptable toxicity. The primary endpoint of this study was an objective response, and secondary endpoints included toxicity, progression-free survival (PFS) and overall survival, as well as clinical benefit response in symptomatic patients.
Forty patients from two institutions were enrolled between September 2004 and November 2005. The most common adverse reactions were fatigue and anorexia, although most of those adverse reactions were tolerable and reversible. One patient developed grade 3 pneumonitis without neutropenia and recovered with appropriate antibiotic treatment. Although no complete response was seen, partial response was obtained in six patients (15, 95% confidence interval, 3.9-26%). Stable disease was noted in 17 patients (43%), and progressive disease in 15 patients (38%). Out of 19 evaluable patients, a clinical benefit response was observed in four patients (21%). The median PFS was 2.0 months, and the median survival time was 4.5 months with a 1-year survival rate of 14.1%.
S-1 as monotherapy had marginal anti-tumor activity with tolerable toxicity in patients with gemcitabine refractory metastatic pancreatic cancer.
吉西他滨单药治疗或含吉西他滨的联合化疗是晚期胰腺癌的标准一线治疗方案。疾病进展后，尚无标准治疗方案可用。在先前的一项II期试验中，据报道S-1显示出相当的疗效，在未经化疗的胰腺癌患者中实现了37.5%的缓解率。本研究评估了S-1在吉西他滨难治性转移性胰腺癌患者中的疗效和毒性。
入选标准为经组织学证实为胰腺腺癌，在接受以吉西他滨为基础的一线化疗时疾病进展得到确认，年龄在20 - 74岁之间，卡诺夫斯基体能状态为80 - 100分，有可测量的转移病灶，血液学、肾脏和肝脏功能良好，并签署书面知情同意书。S-1以40 mg/m²口服，每日两次，共28天，休息14天为一个疗程。重复给药直至疾病进展或出现不可接受的毒性。本研究的主要终点是客观缓解，次要终点包括毒性、无进展生存期（PFS）和总生存期，以及有症状患者的临床获益反应。
2004年9月至2005年11月期间，来自两个机构的40例患者入组。最常见的不良反应是疲劳和厌食，不过大多数不良反应是可耐受且可逆的。1例患者发生3级肺炎，无中性粒细胞减少，经适当抗生素治疗后康复。虽然未观察到完全缓解，但6例患者（15%，95%置信区间，3.9 - 26%）获得部分缓解。17例患者（43%）病情稳定，15例患者（38%）病情进展。在19例可评估患者中，4例患者（21%）观察到临床获益反应。中位PFS为2.0个月，中位生存时间为4.5个月，1年生存率为14.1%。
S-1单药治疗对吉西他滨难治性转移性胰腺癌患者具有一定的抗肿瘤活性，且毒性可耐受。
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