Smith Ian E
Breast Unit, Royal Marsden Hospital, London, UK.
Semin Oncol. 2006 Jun;33(3 Suppl 9):S19-23. doi: 10.1053/j.seminoncol.2006.03.020.
Gemcitabine, an antimetabolite that is incorporated as a triphosphate into DNA, is active as a single agent in first- and subsequent-line treatment of breast cancer, with an overall objective response rate of 26%. It is relatively well tolerated, and its dose-limiting toxicity has usually been neutropenia. Gemcitabine has proven active in combination with paclitaxel and, on this basis, a phase III trial showed a significantly higher response rate than paclitaxel alone (39.3% v 25.6%). The combination also showed a significantly longer median time to progression (5.2 v 2.9 months) and significantly improved median overall survival time (18.5 v 15.8 months). Apart from neutropenia, there was no significant increase in toxicity for the combination. Gemcitabine has also been shown to be active in combination with docetaxel, and a phase III trial has shown that gemcitabine plus docetaxel is as effective as capecitabine plus docetaxel, but with significantly less nonhematologic toxicity. Two-week schedules of gemcitabine plus paclitaxel or docetaxel are currently being investigated, as are combinations with paclitaxel plus trastuzumab, and paclitaxel plus anthracyclines. These results have prompted ongoing trials of gemcitabine in early breast cancer as neoadjuvant and adjuvant therapy.
吉西他滨是一种抗代谢药物，作为三磷酸形式掺入DNA中，作为单药在乳腺癌的一线及后续治疗中具有活性，总体客观缓解率为26%。它耐受性相对较好，其剂量限制性毒性通常为中性粒细胞减少。吉西他滨已被证明与紫杉醇联合使用具有活性，在此基础上，一项III期试验显示联合用药的缓解率显著高于单独使用紫杉醇（39.3%对25.6%）。联合用药还显示出显著更长的中位疾病进展时间（5.2个月对2.9个月）和显著改善的中位总生存时间（18.5个月对15.8个月）。除中性粒细胞减少外，联合用药的毒性没有显著增加。吉西他滨与多西他赛联合使用也显示出活性，一项III期试验表明吉西他滨加多西他赛与卡培他滨加多西他赛疗效相当，但非血液学毒性显著更低。目前正在研究吉西他滨与紫杉醇或多西他赛的两周给药方案，以及与紫杉醇加曲妥珠单抗和紫杉醇加蒽环类药物的联合用药方案。这些结果促使正在进行吉西他滨在早期乳腺癌中作为新辅助和辅助治疗的试验。
