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

BMC Cancer. 2011 Jul 11:11:289. doi: 10.1186/1471-2407-11-289.

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.

Publication types

  • Case Reports
  • Clinical Trial

MeSH terms

  • Adenocarcinoma / blood
  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / surgery
  • Adenocarcinoma, Papillary / blood
  • Adenocarcinoma, Papillary / drug therapy
  • Adenocarcinoma, Papillary / surgery
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Phytogenic / administration & dosage
  • Antineoplastic Agents, Phytogenic / adverse effects
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Area Under Curve
  • Blood Platelets / drug effects*
  • Carboplatin / administration & dosage
  • Carboplatin / adverse effects
  • Carboplatin / pharmacology*
  • Cisplatin / administration & dosage
  • Combined Modality Therapy
  • Cystadenocarcinoma, Serous / blood
  • Cystadenocarcinoma, Serous / drug therapy
  • Cystadenocarcinoma, Serous / surgery
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Resistance, Neoplasm
  • Etoposide / administration & dosage
  • Female
  • Granulosa Cell Tumor / blood
  • Granulosa Cell Tumor / drug therapy
  • Granulosa Cell Tumor / surgery
  • Humans
  • Middle Aged
  • Ovarian Neoplasms / blood
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / surgery
  • Ovariectomy
  • Paclitaxel / administration & dosage
  • Paclitaxel / adverse effects
  • Paclitaxel / pharmacology*
  • Peripheral Nervous System Diseases / chemically induced
  • Salvage Therapy*
  • Tamoxifen / administration & dosage
  • Thrombocytopenia / chemically induced
  • Thrombocytopenia / prevention & control*
  • Treatment Outcome

Substances

  • Antineoplastic Agents, Phytogenic
  • Tamoxifen
  • Etoposide
  • Carboplatin
  • Paclitaxel
  • Cisplatin