Sustained platelet-sparing effect of weekly low dose paclitaxel allows effective, tolerable delivery of extended dose dense weekly carboplatin in platinum resistant/refractory epithelial ovarian cancer

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.Ovarian cancer is the leading cause of death from gynaecologic malignancies in the United Kingdom, and is the fourth most common cause of cancer mortality in women [1]. 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 treat, known as the platinum-free interval (PFI) [4,5]. The PFI is a predictor of response not only to second-line treatment with platinum-based chemotherapy but also other active agents [6]. Stemming from the original paper by Markmann and colleagues in 1991, patients who relapse within 6 months are termed platinum resistant, those who never respond platinum refractory and those who relapse after more than one year platinum sensitive [4]. The term partially sensitive has come into use more recently to describe the patients with a PFI of 6 to 12 months. The probability of response to platinum rechallenge increases with the PFI, from > 60% in patients relapsing > 12 months since last platinum therapy to below 10% in patients relapsing within 6 months [4]. There is increasing evidence, however, that by administering platinum in a 'dose-dense' manner, resistance can be overcome resu