Bennouna Jaafar, Saunders Mark, Douillard Jean-Yves
Centre R Gauducheau, St Herblain, France.
Oncology. 2009;76(5):301-10. doi: 10.1159/000209334. Epub 2009 Mar 20.
5-Fluorouracil (5-FU) has been the most widely used chemotherapeutic agent for metastatic colorectal cancer (mCRC) and 5-FU combination therapy improves efficacy compared with monotherapy. The oral fluoropyrimidine UFT (tegafur-uracil) with leucovorin (LV) improves tolerability and has replaced 5-FU in many regimens. The efficacy and tolerability of UFT with LV in the first-line treatment of mCRC has been demonstrated in a number of phase II studies. In two phase III studies, UFT with LV has been shown to have comparable efficacy and improved tolerability versus intravenous bolus 5-FU, with very few cases of hand-foot syndrome (HFS). Indirect comparisons of UFT and capecitabine suggest that they are comparable in terms of survival. In first-line treatment, UFT in combination with oxaliplatin (TEGAFOX) or irinotecan (TEGAFIRI) is effective and well tolerated, with similar efficacy and tolerability to the corresponding 5-FU- and capecitabine-based combinations, but with a lower incidence of HFS. Alternating cycles of TEGAFOX and TEGAFIRI are effective and well tolerated, and the combination of TEGAFIRI and the targeted monoclonal antibody cetuximab has shown promising activity, similar to that of FOLFIRI plus cetuximab. UFT can be considered a rational replacement for intravenous 5-FU in the first- and second-line treatment of patients with mCRC.
5-氟尿嘧啶(5-FU)一直是转移性结直肠癌(mCRC)中使用最广泛的化疗药物,与单药治疗相比,5-FU联合治疗可提高疗效。口服氟嘧啶优福定(替加氟-尿嘧啶)联合亚叶酸钙(LV)可提高耐受性,在许多治疗方案中已取代了5-FU。多项II期研究证实了优福定联合LV在mCRC一线治疗中的疗效和耐受性。在两项III期研究中,优福定联合LV已显示出与静脉推注5-FU具有相当的疗效且耐受性更好,手足综合征(HFS)病例极少。优福定和卡培他滨的间接比较表明,它们在生存率方面相当。在一线治疗中,优福定联合奥沙利铂(TEGAFOX)或伊立替康(TEGAFIRI)有效且耐受性良好,与相应的基于5-FU和卡培他滨的联合治疗具有相似疗效和耐受性,但HFS发生率较低。TEGAFOX和TEGAFIRI交替周期有效且耐受性良好,TEGAFIRI与靶向单克隆抗体西妥昔单抗联合已显示出有前景的活性,类似于FOLFIRI加西妥昔单抗。在mCRC患者的一线和二线治疗中,优福定可被视为静脉注射5-FU的合理替代药物。