title: Evolving concepts in the management of drug resistant ovarian cancer: dose dense chemotherapy and the reversal of clinical platinum resistance.
abstract: Despite the initially high response rate to standard front-line debulking surgery followed by platinum-based chemotherapy, the relapse rate in ovarian cancer is high and many patients will recur within 6 months of completing platinum based treatment. These patients may still require further chemotherapy despite being considered "platinum resistant". In this setting, response rates to conventionally scheduled second line platinum and non-platinum agents is low, ranging between 5% and 15%. There is an emerging body of evidence that in this scenario, chemotherapeutic activity can be enhanced using unconventionally scheduled "dose-dense" platinum and non-platinum based regimens with improved response rates of up to 65%. Randomised studies to evaluate the impact of this approach on survival in recurrent, platinum resistant disease are urgently required to confirm the promising phase II findings if there is to be a change in the standard of care of patients with platinum resistant disease. In this review we discuss the evolving strategies to overcome resistance in patients with platinum resistant ovarian cancer with a particular focus on alterations in dose schedule as a means of reversing platinum resistance.
authors.affiliation: Division of Experimental Medicine, Imperial College London, Hammersmith Campus, Du Cane Road, W12 0HS London, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Pinato
authors.forename: Janet
authors.initials: J
authors.lastname: Graham
authors.forename: Hani
authors.initials: H
authors.lastname: Gabra
authors.forename: Rohini
authors.initials: R
authors.lastname: Sharma
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000627:therapeutic use*; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage
chemical_list: D009944:Organoplatinum Compounds; D016190:Carboplatin; D017239:Paclitaxel