Michael M, Price T, Ngan S Y, Ganju V, Strickland A H, Muller A, Khamly K, Milner A D, Dilulio J, Matera A, Zalcberg J R, Leong T
Division of Haematology and Medical Oncology, Peter MacCallum Cancer Centre, Locked Bag 1, A'Beckett Street, Melbourne, Victoria 8006, Australia.
Br J Cancer. 2009 Jan 13;100(1):37-43. doi: 10.1038/sj.bjc.6604827. Epub 2008 Dec 16.
Standard chemoradiotherapy with infusional 5FU for locally advanced pancreatic cancer (LAPC) has limited efficacy in this disease. The combination of Capecitabine (Cap) and Gemcitabine (Gem) are synergistic and are potent radiosensitisers. The aim of this phase I trial was thus to determine the highest administered dose of the Cap plus Gem combination with radical radiotherapy (RT) for LAPC. Patients had LAPC, adequate organ function, ECOG PS 0-1. During RT, Gem was escalated from 20-50 mg m(-2) day(-1) (twice per week), and Cap 800-2000 mg m(-2) day(-1) (b.i.d, days 1-5 of each week). Radiotherapy 50.4 Gy/28 fractions/5.5 weeks, using 3D-conformal techniques. Three patients were entered to each dose level (DL). Dose-limiting toxicity(s) (DLTs) were based on treatment-related toxicities. Twenty patients were accrued. Dose level (DL) 1: Cap/Gem; 800/20 mg m(-2) day(-1) (3 patients), DL2: 1000/20 (12 patients), DL3: 1300/30 (5 patients). Dose-limiting toxicities were observed in DL3; grade 3 dehydration (1 patient) and grade 3 diarrhoea and dehydration (1 patient). Dose level 2 was the recommend phase 2 dose. Disease control rate was 75%: PR=15%, SD=60%. Median overall survival was 11.2 months. The addition of Cap and Gem to radical RT was feasible and active and achieved at relatively low doses.
对于局部晚期胰腺癌（LAPC），采用5-氟尿嘧啶持续输注的标准放化疗对该疾病的疗效有限。卡培他滨（Cap）和吉西他滨（Gem）联合使用具有协同作用，且是强效放射增敏剂。因此，这项I期试验的目的是确定Cap加Gem联合根治性放疗（RT）用于LAPC的最高给药剂量。患者患有LAPC，器官功能良好，东部肿瘤协作组（ECOG）体能状态评分为0 - 1。在放疗期间，Gem的剂量从20 - 50 mg m(-2) 天(-1)（每周两次）逐步增加，Cap为800 - 2000 mg m(-2) 天(-1)（每日两次，每周第1 - 5天）。采用三维适形技术进行放疗，剂量为50.4 Gy/28次/5.5周。每个剂量水平（DL）纳入3名患者。剂量限制毒性（DLT）基于与治疗相关的毒性。共纳入20例患者。剂量水平（DL）1：Cap/Gem；800/20 mg m(-2) 天(-1)（3例患者），DL2：1000/20（12例患者），DL3：1300/30（5例患者）。在DL3观察到剂量限制毒性；3级脱水（1例患者）以及3级腹泻和脱水（1例患者）。剂量水平2为推荐的II期剂量。疾病控制率为75%：部分缓解（PR）=15%，疾病稳定（SD）=60%。中位总生存期为11.2个月。在根治性放疗中加入Cap和Gem是可行且有效的，并且在相对较低剂量下即可实现。
