Abstract
BackgroundPlatinum 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.MethodsWe 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.ResultsWe 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.ConclusionsWe 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.
Highlights
Platinum agents have shown demonstrable activity in the treatment of patients with platinum resistant, recurrent ovarian cancer when delivered in a “dose-dense” fashion
We demonstrate that the addition of low dose paclitaxel allows delivery of weekly dose dense carboplatin AUC 3 by maintaining platelet counts without compromising dose dense carboplatin mediated tumour response
Seven consecutive patients with platinum resistant epithelial ovarian cancer, with grade ≥ 2 neuropathic symptoms at the time of commencement of dose dense therapy or who developed neuropathy whilst receiving weekly combination carboplatin AUC 3 and paclitaxel 70 mg/m2, were treated with carboplatin (AUC 3) and paclitaxel (20 mg/m2) administered day 1, 8, 15 q4weekly
Summary
Platinum agents have shown demonstrable activity in the treatment of patients with platinum resistant, recurrent ovarian cancer when delivered in a “dose-dense” fashion. Despite 70-80% overall response to initial therapy, the majority of patients will experience disease relapse and will require further chemotherapy [2,3]. Several therapeutic options are available and the decision as to which therapy to commence is dependent on the time from last platinum chemotherapy to decision to be overcome resulting in significant improvements in response [7]. The concept of dose manipulation, in particular the delivery of dose dense chemotherapy is not novel and has been extensively studied in a number of tumour types in particular breast cancer where significant improvements in both disease free survival and overall survival have been reported [10]. Use of adjuvant dose dense weekly paclitaxel in combination with conventional platinum has demonstrated significant improvement in progression free survival and overall survival in ovarian cancer [11]
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