Oman M, Lundqvist S, Gustavsson B, Hafström L O, Naredi P
Department of surgical and perioperative science; Surgery, Umeå University Hospital, 90185, Umeå, SE, Sweden.
Cancer Chemother Pharmacol. 2005 Dec;56(6):603-9. doi: 10.1007/s00280-005-1012-5. Epub 2005 Jul 27.
Systemic palliative treatment with chemotherapy against advanced pancreas cancer has low effectiveness despite considerable toxicity.
To investigate the safety, toxicity and tumour response of intraperitoneal 5-Fluorouracil (5-FU) with intravenous Leucovorin and to monitor 5-FU pharmacokinetics in plasma during intraperitoneal instillation with and without vasopressin in patients with non-resectable pancreas cancer.
PATIENTS/METHODS: Between 1994 and 2003, 68 patients with non-resectable pancreas cancer TNM stage III and IV, were enrolled to receive intraperitoneal5-FU instillation 750-1500 mg/m2 and intravenous Leucovorin 100 mg/m2 for two days every third week. Tumour response, performance status and toxicity were recorded. Seventeen patients were also treated with intravenous vasopressin 0.1 IU/minute for 180 minutes, during intraperitoneal 5-FU instillation. Area under the curve (AUC) and peak concentration (Cmax) of 5-FU in plasma were analysed.
The treatment was well tolerated with minor toxicity. One complete response (54.1+ months) and 2 partial responses were observed. Time to progression was 4.4 months (0.8-54.1+), and median survival was 8.0 months (0.8-54.1+). There was a significant reduction of 5-FU Cmax in plasma the second day of treatment if vasopressin was used (3.4+/-2.5 and 6.1+/-5.4 mumol/l, respectively, p<0.05). 5-FU AUC in plasma was not significantly affected by vasopressin either day of treatment.
Intraperitoneal 5-FU is a safe treatment with low toxicity to patients with non-resectable pancreas cancer. Tumour response was 4.4% and median survival time 8.0 months. Addition of vasopressin did not significantly decrease plasma 5-FU AUC but reduced Cmax on day 2 of treatment.
针对晚期胰腺癌的全身姑息性化疗效果不佳，且毒性较大。
研究腹腔内注射5-氟尿嘧啶（5-FU）联合静脉注射亚叶酸钙的安全性、毒性及肿瘤反应，并监测不可切除胰腺癌患者在腹腔内注射5-FU时，无论有无血管加压素情况下血浆中5-FU的药代动力学。
患者/方法：1994年至2003年间，68例TNM分期为III期和IV期的不可切除胰腺癌患者入组，每三周接受为期两天的腹腔内注射5-FU 750 - 1500 mg/m²及静脉注射亚叶酸钙100 mg/m²治疗。记录肿瘤反应、身体状况及毒性。17例患者在腹腔内注射5-FU期间还接受了静脉注射血管加压素0.1 IU/分钟，持续180分钟的治疗。分析血浆中5-FU的曲线下面积（AUC）和峰值浓度（Cmax）。
该治疗耐受性良好，毒性较小。观察到1例完全缓解（54.1 +个月）和2例部分缓解。疾病进展时间为4.4个月（0.8 - 54.1 +），中位生存期为8.0个月（0.8 - 54.1 +）。若使用血管加压素，治疗第二天血浆中5-FU的Cmax显著降低（分别为3.4±2.5和6.1±5.4 μmol/l，p < 0.05）。治疗当天血管加压素对血浆中5-FU的AUC均无显著影响。
腹腔内注射5-FU对不可切除胰腺癌患者是一种安全、低毒的治疗方法。肿瘤反应率为4.4%，中位生存时间为8.0个月。添加血管加压素并未显著降低血浆中5-FU的AUC，但降低了治疗第二天的Cmax。
