Metro G, Cappuzzo F, Finocchiaro G, Toschi L, Crinò L
Bellaria Hospital, Department of Medical Oncology, Bologna, Italy.
Ann Oncol. 2006 May;17 Suppl 5:v37-46. doi: 10.1093/annonc/mdj948.
Gemcitabine, a pyrimidine nucleoside antimetabolite, is one of the most promising new cytotoxic agents. The drug has shown activity in a variety of solid tumors, but appears to be most active in the treatment of non-small cell lung cancer. In this disease, several Italian investigators have evaluated gemcitabine in phase II and III clinical trials. Due to preclinical synergism with cisplatin, the Italian Lung Cancer Project played an important role to assess the efficacy and activity of the gemcitabine-cisplatin combination along with the best doses and schedule to adopt, thus leading to gemcitabine approval for first line treatment of advanced non-small cell lung cancer. Several Italian studies have also investigated gemcitabine non-platinum based combinations, gemcitabine in third generation platinum-based triplets and gemcitabine as second line therapy, but all these studies led to conflicting and inconclusive results. The low toxicity profile makes the drug a valid option for unfit and elderly patients. The Multicenter Italian Lung Cancer in the Elderly Study was a phase III randomized trial conducted in elderly patients with advanced non-small cell lung cancer that showed that single agent gemcitabine is at least as effective as either single agent vinorelbine or the combination of gemcitabine and vinorelbine. In the neoadjuvant treatment of stage III disease, a number of phase II studies with third generation platinum-based doublets or triplets have been conducted by Italian investigators with encouraging results. Current clinical trials are addressing the role of gemcitabine in combination with new targeted therapies. Future studies should be designed in order to identify subgroups of patients who are more likely to benefit from gemcitabine chemotherapy.
吉西他滨是一种嘧啶核苷抗代谢物，是最有前景的新型细胞毒性药物之一。该药物已在多种实体瘤中显示出活性，但似乎在非小细胞肺癌治疗中活性最强。在这种疾病中，几位意大利研究人员在II期和III期临床试验中对吉西他滨进行了评估。由于吉西他滨与顺铂在临床前具有协同作用，意大利肺癌项目在评估吉西他滨 - 顺铂联合用药的疗效和活性以及最佳剂量和给药方案方面发挥了重要作用，从而使吉西他滨获批用于晚期非小细胞肺癌的一线治疗。几项意大利研究还调查了吉西他滨的非铂类联合用药、吉西他滨在第三代铂类三联疗法中的应用以及吉西他滨作为二线治疗，但所有这些研究都得出了相互矛盾且无定论的结果。低毒性特征使该药物成为身体不适和老年患者的有效选择。意大利老年肺癌多中心研究是一项针对晚期非小细胞肺癌老年患者进行的III期随机试验，结果表明单药吉西他滨至少与单药长春瑞滨或吉西他滨与长春瑞滨联合用药一样有效。在III期疾病的新辅助治疗中，意大利研究人员进行了多项关于第三代铂类双联或三联疗法的II期研究，结果令人鼓舞。目前的临床试验正在探讨吉西他滨与新的靶向治疗联合应用的作用。未来的研究应进行设计，以确定更可能从吉西他滨化疗中获益的患者亚组。
