Sumpter K, Harper-Wynne C, Cunningham D, Rao S, Tebbutt N, Norman A R, Ward C, Iveson T, Nicolson M, Hickish T, Hill M, Oates J
Department of Medicine, Royal Marsden Hospital NHS Trust, Down's Road, Sutton, Surrey SM2 5PT, UK.
Br J Cancer. 2005 Jun 6;92(11):1976-83. doi: 10.1038/sj.bjc.6602572.
The purpose of the study was to establish the optimal dose of capecitabine (X) to be used within a multicentre, randomised study evaluating the potential roles of oxaliplatin (O) and X in chemonaive patients (pts) with advanced oesophagogastric cancer. Two by two design was used, and pts were randomised to one of four regimens and stratified for extent of disease, performance status (PS) and centre. The treatment regimens are epirubicin, cisplatin, 5-fluorouracil (ECF), EOF, ECX or EOX. Doses: E 50 mg m(-2), C 60 mg m(-2) and O 130 mg m(-2) i.v. 3 weekly; F 200 mg m(-2) day(-1) i.v. and X 500 mg m(-2) b.i.d.(-1) (escalated to 625 mg m(-2) b.i.d.(-1) after results of first interim analysis) p.o., continuously. First interim analysis was performed when 80 pts had been randomised. Dose-limiting fluoropyrimidine toxicities were stomatitis, palmar plantar erythema (PPE) and diarrhoea; 5.1% of X-treated pts experienced grade 3/4 toxicity. Protocol planned dose escalation of X to 625 mg m(-2) b.i.d.(-1) was instituted and a second interim analysis has been performed; results are presented in this paper. A total of 204 pts were randomised at the time of the protocol planned 2nd interim analysis. Grade 3/4 fluoropyrimidine-related toxicity was seen in 13.7% pts receiving F, 8.4% pts receiving X 500 mg m(-2) b.i.d.(-1) and 14.7% pts receiving X 625 mg m(-2) b.i.d.(-1). Combined complete and partial response rates were ECF 31% (95% CI 18.7-46.3), EOF 39% (95% CI 25.9-53.1), ECX 35% (95% CI 21.4-50.3), EOX 48% (95% CI 33.3-62.8). Grade 3/4 fluoropyrimidine toxicity affected 14.7% of pts treated with X 625 mg m(-2) b.i.d.(-1), which is similar to that observed with F, confirming this to be the optimal dose. The replacement of C by O and F by X does not appear to impair efficacy. The trial continues to total accrual of 1000 pts.
本研究的目的是确定卡培他滨（X）的最佳剂量，该剂量将用于一项多中心随机研究，评估奥沙利铂（O）和X在初治晚期食管胃癌患者中的潜在作用。采用二乘二设计，患者被随机分配至四种治疗方案之一，并根据疾病范围、体能状态（PS）和中心进行分层。治疗方案为表柔比星、顺铂、5-氟尿嘧啶（ECF）、EOF、ECX或EOX。剂量：表柔比星50mg/m²、顺铂60mg/m²和奥沙利铂130mg/m²静脉注射，每3周一次；氟尿嘧啶200mg/m²第1天静脉注射，卡培他滨500mg/m²每日两次口服（在首次中期分析结果后增至625mg/m²每日两次），持续给药。当80例患者被随机分组后进行首次中期分析。氟嘧啶类药物的剂量限制性毒性为口腔炎、手足红斑（PPE）和腹泻；接受卡培他滨治疗的患者中有5.1%出现3/4级毒性。按照方案计划将卡培他滨剂量增至625mg/m²每日两次，并进行了第二次中期分析；本文给出了结果。在方案计划的第二次中期分析时，共有204例患者被随机分组。接受氟尿嘧啶治疗的患者中有13.7%、接受500mg/m²每日两次卡培他滨治疗的患者中有8.4%、接受625mg/m²每日两次卡培他滨治疗的患者中有14.7%出现3/4级氟嘧啶类药物相关毒性。完全缓解和部分缓解的联合率分别为：ECF 31%（95%CI 18.7-46.3）、EOF 39%（95%CI 25.9-53.1）、ECX 35%（95%CI 21.4-50.3）、EOX 48%（95%CI 33.3-62.8）。接受625mg/m²每日两次卡培他滨治疗的患者中有14.7%出现3/4级氟嘧啶类药物毒性，这与接受氟尿嘧啶治疗患者中观察到的毒性相似，证实这是最佳剂量。用奥沙利铂替代顺铂以及用卡培他滨替代氟尿嘧啶似乎并未损害疗效。该试验继续进行，直至总共入组1000例患者。
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