Pedersen A G
Eli Lilly Research Center Limited, Windlesham, UK.
Semin Oncol. 1997 Apr;24(2 Suppl 7):S7-64-S7-68.
Gemcitabine is a novel nucleoside analogue with a unique mechanism of action. In light of its good single-agent activity in several solid tumors, generally mild toxicity profile, and potential for synergy, combination phase I studies with other active chemotherapeutic agents have been conducted. In two studies the combination of gemcitabine and carboplatin was used to treat patients with non-small cell lung cancer. Gemcitabine was administered weekly x 3 every 4 weeks, and carboplatin was given on day 1. Although dose-limiting myelotoxicity was observed, encouraging activity was noted. In other studies patients with recurrent or persistent ovarian cancer or with refractory solid tumors were treated with weekly gemcitabine and paclitaxel on a 28-day schedule or with both drugs given every 2 weeks. Dose escalation was possible and toxicities were manageable. The effect of sequence of drug administration on the toxicity profile was also examined. Further trials to establish the efficacy of these promising approaches as well as combinations of all three drugs are needed.
吉西他滨是一种具有独特作用机制的新型核苷类似物。鉴于其在多种实体瘤中具有良好的单药活性、总体毒性较轻以及具有协同作用的潜力，已开展了其与其他活性化疗药物联合应用的I期研究。在两项研究中，吉西他滨与卡铂联合用于治疗非小细胞肺癌患者。吉西他滨每4周每周给药1次，共3次，卡铂在第1天给药。虽然观察到了剂量限制性骨髓毒性，但也注意到了令人鼓舞的活性。在其他研究中，复发性或持续性卵巢癌患者或难治性实体瘤患者接受了按28天疗程的每周吉西他滨和紫杉醇治疗，或两种药物每2周给药一次。可以进行剂量递增且毒性可控。还研究了给药顺序对毒性特征的影响。需要进一步开展试验以确定这些有前景的方法以及三种药物联合应用的疗效。
