Hochster Howard S, Hart Lowell L, Ramanathan Ramesh K, Childs Barrett H, Hainsworth John D, Cohn Allen L, Wong Lucas, Fehrenbacher Louis, Abubakr Yousif, Saif M Wasif, Schwartzberg Lee, Hedrick Eric
New York University Cancer Institute, 160 East 34th St, New York, NY 10016, USA.
J Clin Oncol. 2008 Jul 20;26(21):3523-9. doi: 10.1200/JCO.2007.15.4138.
To evaluate the safety and efficacy of three oxaliplatin and fluoropyrimidine regimens, with or without bevacizumab, as first-line treatment for metastatic colorectal cancer (CRC).
Patients with histologically documented metastatic or recurrent CRC and no prior treatment for advanced disease were randomly assigned to mFOLFOX6 (bolus and infusion fluorouracil [FU] and leucovorin [LV] with oxaliplatin), bFOL (bolus FU and low-dose LV with oxaliplatin), or CapeOx (capecitabine with oxaliplatin), respectively (Three Regimens of Eloxatin Evaluation [TREE-1]). The study was later modified such that subsequent patients were randomized to the same regimens plus bevacizumab (TREE-2).
A total of 150 and 223 patients were randomly assigned in the TREE-1 and TREE-2 cohorts, respectively. Incidence of grade 3/4 treatment-related adverse events during the first 12 weeks of treatment were 59%, 36%, and 67% for mFOLFOX6, bFOL, and CapeOx, respectively, (TREE-1) and 59%, 51%, and 56% for the corresponding treatments plus bevacizumab (TREE-2; primary end point). CapeOx toxicity in TREE-1 included grade 3/4 diarrhea (31%) and dehydration (27%); capecitabine dose reduction to 1,700 mg/m(2)/d in TREE-2 resulted in improved tolerance. Overall response rates were 41%, 20%, and 27% (TREE-1) and 52%, 39%, and 46% (TREE-2); median overall survival (OS) was 19.2, 17.9, and 17.2 months (TREE-1) and 26.1, 20.4, and 24.6 months (TREE-2). For all treated patients, median OS was 18.2 months (95% CI, 14.5 to 21.6; TREE-1) and 23.7 months (95% CI, 21.3 to 26.8; TREE-2).
The addition of bevacizumab to oxaliplatin and fluoropyrimidine regimens is well tolerated as first-line treatment of mCRC and does not markedly change overall toxicity. CapeOx tolerability and efficacy is improved with reduced-dose capecitabine. First-line oxaliplatin and fluoropyrimidine-based therapy plus bevacizumab resulted in a median OS of approximately 2 years.
评估三种含奥沙利铂和氟嘧啶方案（加或不加贝伐单抗）作为转移性结直肠癌（CRC）一线治疗的安全性和疗效。
组织学确诊为转移性或复发性CRC且未接受过晚期疾病治疗的患者被随机分配至mFOLFOX6（推注和输注氟尿嘧啶[FU]及亚叶酸钙[LV]联合奥沙利铂）、bFOL（推注FU和低剂量LV联合奥沙利铂）或 CapeOx（卡培他滨联合奥沙利铂）组（奥沙利铂评估的三种方案[TREE-1]）。该研究后来进行了修改，后续患者被随机分配至相同方案加贝伐单抗组（TREE-2）。
TREE-1和TREE-2队列分别随机分配了150例和223例患者。治疗前12周内3/4级治疗相关不良事件的发生率，mFOLFOX6、bFOL和CapeOx在TREE-1中分别为59%、36%和67%，相应治疗加贝伐单抗在TREE-2中分别为59%、51%和56%（主要终点）。TREE-1中CapeOx的毒性包括3/4级腹泻（31%）和脱水（27%）；TREE-2中卡培他滨剂量减至1700mg/m²/d后耐受性改善。总体缓解率在TREE-1中分别为41%、20%和27%，在TREE-2中分别为：52%、39%和46%；中位总生存期（OS）在TREE-1中分别为19.2个月、17.9个月和17.2个月，在TREE-2中分别为26.1个月、20.4个月和24.个月。所有接受治疗的患者，中位OS在TREE-1中为18.2个月（95%CI，14.5至21.6），在TREE-2中为23.7个月（95%CI，21.3至26.8）。
奥沙利铂和氟嘧啶方案加用贝伐单抗作为mCRC一线治疗耐受性良好，且未显著改变总体毒性。降低卡培他滨剂量可改善CapeOx的耐受性和疗效。一线奥沙利铂和氟嘧啶类药物联合贝伐单抗治疗的中位OS约为2年。
