title: 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.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Experimental Medicine, Imperial College, London, UK. r.sharma@imperial.ac.uk
authors: Rohini
authors: R
authors: Sharma
authors: Janet
authors: J
authors: Graham
authors: Sarah
authors: S
authors: Blagden
authors: Hani
authors: H
authors: Gabra
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000188:drug therapy* / Q000601:surgery; D000231:Adenocarcinoma, Papillary / Q000097:blood / Q000188:drug therapy / Q000601:surgery; D000368:Aged; D000369:Aged, 80 and over; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019540:Area Under Curve; D001792:Blood Platelets / Q000187:drug effects*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D018284:Cystadenocarcinoma, Serous / Q000097:blood / Q000188:drug therapy / Q000601:surgery; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006106:Granulosa Cell Tumor / Q000097:blood / Q000188:drug therapy / Q000601:surgery; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000601:surgery; D010052:Ovariectomy; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced; D016879:Salvage Therapy; D013629:Tamoxifen / Q000008:administration & dosage; D013921:Thrombocytopenia / Q000139:chemically induced / Q000517:prevention & control*; D016896:Treatment Outcome
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D013629:Tamoxifen; D005047:Etoposide; D016190:Carboplatin; D017239:Paclitaxel; D002945:Cisplatin