Phase I study on pegylated liposomal doxorubicin in combination with docetaxel for patients with platinum-resistant or partially platinum-sensitive epithelial ovarian cancer: The Kansai Clinical Oncology Group study

J Cancer Res Ther. 2019 Oct-Dec;15(6):1201-1206. doi: 10.4103/jcrt.JCRT_742_16.

Abstract

Context: In platinum-resistant ovarian cancer, single-agent chemotherapy is recommended for the reduction of adverse events. However, in clinical practice, some patients can tolerate drug-specific adverse events.

Aims: We assessed the safety of pegylated liposomal doxorubicin (PEG-LD) and docetaxel regimen in the first cycle of ovarian cancer.

Settings and design: We performed a phase I study to evaluate the combination therapy of PEG-LD and docetaxel.

Materials and methods: We recruited five patients with recurrent ovarian cancer within 12 months of first-line platinum-based chemotherapy. All patients had measurable disease severity. PEG-LD and docetaxel were intravenously administered on day 1 and every 21 days using three dose levels: 25 mg/m2 PEG-LD and 50 mg/m2 docetaxel; 30 mg/m2 PEG-LD and 50 mg/m2 docetaxel; and 30 mg/m2 PEG-LD and 60 mg/m2 docetaxel.

Statistical analysis used: We defined the maximum tolerated dose of the combination therapy based on the modified Fibonacci method.

Results: Five patients were enrolled in this study. The median treatment-free interval was 5.5 months. Two dose-limiting toxicities (Grade 4 neutropenia) were observed in two patients. One complete response, one partial response, one stable disease, and two progressive disease cases were observed. The overall response rate was 2/5, and the disease control rate was 3/5. The median overall survival was 7.4 months.

Conclusions: We determined that 25 mg/m2 of PEG-LD and 50 mg/m2 of docetaxel were safe and effective doses. This preliminary efficacy and safety data should be further investigated in a Phase II trial.

Keywords: Docetaxel; ovarian cancer; pegylated liposomal doxorubicin; platinum resistance; platinum sensitivity; therapeutic dose.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Ovarian Epithelial / diagnosis
  • Carcinoma, Ovarian Epithelial / drug therapy*
  • Carcinoma, Ovarian Epithelial / mortality
  • Docetaxel / administration & dosage
  • Doxorubicin / administration & dosage
  • Doxorubicin / analogs & derivatives
  • Drug Resistance, Neoplasm*
  • Female
  • Humans
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Ovarian Neoplasms / diagnosis
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / mortality
  • Platinum / pharmacology
  • Platinum / therapeutic use
  • Polyethylene Glycols / administration & dosage
  • Retreatment
  • Treatment Outcome

Substances

  • liposomal doxorubicin
  • Docetaxel
  • Polyethylene Glycols
  • Platinum
  • Doxorubicin