Phase II study of the combination of pegylated liposomal doxorubicin and topotecan in platinum-resistant ovarian cancer

Int J Gynecol Cancer. 2006 Jan-Feb;16(1):65-70. doi: 10.1111/j.1525-1438.2006.00298.x.

Abstract

The combination of liposomal doxorubicin and topotecan was evaluated in a phase II study in patients with platinum-resistant ovarian cancer. Twenty-seven patients received liposomal doxorubicin (30 mg/m(2)) infused at day 1, followed by topotecan (1 mg/m(2)) infusion daily for 5 days. Cycles were repeated every 21 days. This combination regimen showed an overall response rate of 28%. Median time to progression was 30 weeks, with a median overall survival of 40 weeks. Grade 3/4 neutropenia was shown in 70% of patients and grade 3/4 thrombopenia in 41% of patients. Neutropenic fever was reported in 11% of patients. After reviewing the first 12 patients, the internal review board decided to administer topotecan at a dose of 0.75 mg/m(2) and liposomal doxorubicin at 40 mg/m(2) for the remainder of the study. However, this adjustment did not lead to reduction in bone marrow toxicity nor to an improvement in dose intensity. Palmar-plantar erythrodysesthesia and mucositis were more reported in the second cohort but usually mild. The combination of liposomal doxorubicin and topotecan demonstrates favorable response data in platinum-resistant ovarian cancer. However, substantial bone marrow toxicity limits further clinical use.

Publication types

  • Clinical Trial, Phase II
  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Antibiotics, Antineoplastic / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Cisplatin / administration & dosage*
  • Dose-Response Relationship, Drug
  • Doxorubicin / administration & dosage
  • Drug Administration Schedule
  • Drug Resistance, Neoplasm*
  • Female
  • Humans
  • Liposomes
  • Maximum Tolerated Dose
  • Middle Aged
  • Neoplasm Staging
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / mortality*
  • Ovarian Neoplasms / pathology
  • Prognosis
  • Risk Assessment
  • Survival Rate
  • Topotecan / administration & dosage
  • Treatment Outcome

Substances

  • Antibiotics, Antineoplastic
  • Liposomes
  • Topotecan
  • Doxorubicin
  • Cisplatin