Department of Experimental Medicine, Imperial College, London, UK.
BMC Cancer. 2011 Jul 11;11:289. doi: 10.1186/1471-2407-11-289.
Platinum agents have shown demonstrable activity in the treatment of patients with platinum resistant, recurrent ovarian cancer when delivered in a "dose-dense" fashion. However, the development of thrombocytopenia limits the weekly administration of carboplatin to no greater than AUC 2. Paclitaxel has a well-described platelet sparing effect however its use to explicitly provide thromboprotection in the context of dose dense carboplatin has not been explored.
We treated seven patients with platinum resistant ovarian cancer who had previously received paclitaxel or who had developed significant peripheral neuropathy precluding the use of further full dose weekly paclitaxel.
We were able to deliver carboplatin AUC 3 and paclitaxel 20 mg/m2 with no thrombocytopenia or worsening of neuropathic side-effects, and with good activity.
We conclude that this regimen may be feasible and active, and could be formally developed as a "platinum-focussed dose-dense scaffold" into which targeted therapies that reverse platinum resistance can be incorporated, and merits further evaluation.
铂类药物在治疗铂类耐药、复发性卵巢癌患者时,以“剂量密集”的方式给药,已显示出明显的疗效。然而,血小板减少症的发展限制了卡铂的每周给药剂量不超过 AUC 2。紫杉醇具有明确的血小板保护作用,但其在剂量密集型卡铂中的应用以明确提供血栓保护作用尚未得到探索。
我们治疗了 7 例铂类耐药的卵巢癌患者,这些患者先前接受过紫杉醇治疗,或已出现严重的周围神经病变,从而排除了进一步使用全剂量每周紫杉醇的可能性。
我们能够给予卡铂 AUC 3 和紫杉醇 20mg/m2,没有血小板减少症或神经毒性副作用的恶化,并且具有良好的疗效。
我们得出结论,该方案可能是可行和有效的,可以作为一种“以铂类为重点的剂量密集支架”进行正式开发,其中可以加入逆转铂类耐药的靶向治疗药物,值得进一步评估。