Woodward Emma J, Twelves Chris
St James's Institute of Oncology, Leeds, UK.
Curr Clin Pharmacol. 2010 Aug;5(3):226-31. doi: 10.2174/157488410791498725.
The taxanes are widely used in the cytotoxic treatment of many solid tumours. Their optimal scheduling, however, remains unconfirmed. Here we review the development of both paclitaxel and docetaxel to identify evidence influencing the choice of schedule. Early work with paclitaxel identified that it exhibits non-linear pharmacokinetics which has important clinical implications. Paclitaxel has been administered with a wide range of infusion times, especially 3-weekly and recently weekly schedules. Clinical activity of a weekly schedule appears at least non-inferior, and, in certain circumstances superior, to the 3-weekly schedule, with improved tolerability. Similarly, docetaxel has been investigated for 3-weekly versus weekly schedule, reporting equivalent efficacy and improved side effect profile for weekly dosing with regards myelosuppression. Both paclitaxel and docetaxel are often used with the monoclonal antibodies trastuzumab and bevacizumab. It would appear that in this setting, activity may be again improved by administering the taxane weekly, especially in combination with trastuzumab. A further recent development is the use of nab-paclitaxel, nanoparticle albumin-bound paclitaxel; this Cremaphor EC-free preparation allows shorter infusion times without premedication. Benefits of a weekly schedule with this newer drug are also emerging from the limited randomised data. Whether the possibly greater efficacy of weekly paclitaxel in particular reflects a biological effect of more frequent exposure of cancer cells to the cytotoxic is less clear as this schedule also allows a higher dose intensity to be delivered. Nevertheless, that after more than 20 years, weekly administration has emerged as the optimal schedule, especially for paclitaxel. In practice, the choice of schedule is a balance between the better tolerability (and possibly efficacy) of weekly treatment balanced against the inconvenience for both the patient and clinic of more frequent visits for chemotherapy.
紫杉烷类药物广泛应用于多种实体瘤的细胞毒性治疗。然而，其最佳给药方案仍未确定。在此，我们回顾紫杉醇和多西他赛的研发历程，以确定影响给药方案选择的证据。早期对紫杉醇的研究发现，它呈现非线性药代动力学，这具有重要的临床意义。紫杉醇的给药时间范围很广，尤其是每3周一次和最近的每周一次给药方案。每周给药方案的临床活性至少不劣于每3周一次的方案，并且在某些情况下更优，耐受性也有所改善。同样，多西他赛也对每3周一次与每周一次的给药方案进行了研究，结果显示每周给药在骨髓抑制方面疗效相当且副作用有所改善。紫杉醇和多西他赛常与单克隆抗体曲妥珠单抗和贝伐单抗联合使用。在这种情况下，每周给药紫杉烷类药物似乎可再次提高活性，尤其是与曲妥珠单抗联合使用时。最近的另一项进展是使用纳米白蛋白结合型紫杉醇（nab - 紫杉醇）；这种不含聚氧乙烯蓖麻油（Cremaphor EC）的制剂允许更短的输注时间且无需预处理。有限的随机数据也显示了这种新型药物每周给药方案的益处。每周使用紫杉醇可能具有更高疗效，这究竟是更频繁地使癌细胞暴露于细胞毒性药物的生物学效应，还是因为该方案允许更高的剂量强度，目前尚不清楚。尽管如此，经过20多年的发展，每周给药已成为最佳方案，尤其是对于紫杉醇而言。在实际应用中，给药方案的选择需要在每周治疗更好的耐受性（以及可能的疗效）与患者和诊所因更频繁就诊进行化疗带来的不便之间进行权衡。
