Tsavaris Nicolas, Kosmas Christos, Skopelitis Helias, Gouveris Panagiotis, Kopterides Petros, Loukeris Dioynissis, Sigala Frantzeska, Zorbala-Sypsa Alexandra, Felekouras Evangelos, Papalambros Efstathios
Department of Pathophysiology, Oncology Unit, "Metaxa" Memorial Cancer Hospital, 18537 Piraeus, Greece.
Invest New Drugs. 2005 Aug;23(4):369-75. doi: 10.1007/s10637-005-1446-y.
The present study was conducted to evaluate the efficacy and safety of the combination of Oxaliplatin, Leucovorin and 5-FU as second line therapy, following relapse to Gemcitabine, in patients with advanced adenocarcinoma of the pancreas.
Patients with advanced pancreatic cancer previously treated with Gemcitabine were included in the study. All patients had histologically or cytologically confirmed adenocarcinoma of the pancreas that was unresectable, locally advanced or metastatic. Treatment consisted of Oxaliplatin 50 mg/m(2) (2-hour iv infusion), followed by Leucovorin 50 mg/m(2) (i.v. bolus) and 500 mg/m(2) 5-FU (1-hour iv infusion), administered weekly, until unacceptable toxicity or disease progression. Objective tumour response and toxicity were evaluated according to World Health Organisation (WHO) criteria.
A total of 30 patients, 20 men and 10 women, median age 63 years (range 52-71 years) and Karnofsky Performance Status (PS) of > or =50 entered the study. The majority of patients (96%) had locally advanced disease. A total of 380 doses of chemotherapy were delivered, a median of 12 doses per patient. Partial responses were observed in 7 patients (PR 23.3%), stable disease in 9 (SD 30.0%), while 14 patients progressed (PD 46.7%). Improved PS was observed in 18 (42.8%) patients. Patients that had responded to first-line Gemcitabine treatment were found more likely to respond or stabilize their disease with second-line treatment. The median duration of response was 22 weeks, and median overall survival was 25 weeks, Grade 3/4 toxicity expressed per chemotherapy dose included leukopenia 16%, anemia 3.2%, thrombocytopenia 3.2%, diarrhea 14.2%, fatigue 16.1% and neurotoxicity 4.2%. Eight patients (27%) suffered a febrile neutropenic event managed successfully with oral antibiotic home therapy, while 17 patients required G-CSF support. There were no treatment related deaths.
The combination of Oxaliplatin, Leucovorin and 5-FU was tolerated with manageable toxicity, offering encouraging activity as second-line treatment of patients with advanced or metastatic pancreatic adenocarcinoma, previously treated with Gemcitabine. Additional studies are warranted with this regimen in Gemcitabine relapsed pancreatic cancer patients.
本研究旨在评估奥沙利铂、亚叶酸钙和5-氟尿嘧啶联合用药作为二线治疗方案，在吉西他滨治疗后复发的晚期胰腺癌患者中的疗效和安全性。
研究纳入了先前接受过吉西他滨治疗的晚期胰腺癌患者。所有患者均经组织学或细胞学确诊为胰腺癌，且无法切除、局部晚期或已发生转移。治疗方案为奥沙利铂50mg/m²（静脉滴注2小时），随后是亚叶酸钙50mg/m²（静脉推注）和5-氟尿嘧啶500mg/m²（静脉滴注1小时），每周给药一次，直至出现不可接受的毒性或疾病进展。根据世界卫生组织（WHO）标准评估客观肿瘤反应和毒性。
共有30例患者进入研究，其中男性20例，女性10例，中位年龄63岁（范围52 - 71岁），卡诺夫斯基体能状态（PS）≥50。大多数患者（96%）为局部晚期疾病。共进行了380次化疗给药，每位患者中位给药12次。7例患者出现部分缓解（PR 23.3%），9例病情稳定（SD 30.0%），14例患者病情进展（PD 46.7%）。18例（42.8%）患者的PS有所改善。发现对一线吉西他滨治疗有反应的患者更有可能对二线治疗产生反应或病情稳定。中位缓解持续时间为22周，中位总生存期为25周。每化疗剂量的3/4级毒性包括白细胞减少16%、贫血3.2%、血小板减少3.2%、腹泻14.2%、疲劳16.1%和神经毒性4.2%。8例患者（27%）发生发热性中性粒细胞减少事件，通过口服抗生素居家治疗成功处理，17例患者需要G-CSF支持。无治疗相关死亡。
奥沙利铂、亚叶酸钙和5-氟尿嘧啶联合用药耐受性良好，毒性可控，作为先前接受过吉西他滨治疗的晚期或转移性胰腺腺癌患者的二线治疗方案，显示出令人鼓舞的活性。有必要对该方案在吉西他滨复发胰腺癌患者中进行进一步研究。
