A phase II study of irinotecan and pegylated liposomal doxorubicin in platinum-resistant recurrent ovarian cancer (Tohoku Gynecologic Cancer Unit 104 study)

Cancer Chemother Pharmacol. 2017 Aug;80(2):355-361. doi: 10.1007/s00280-017-3363-0. Epub 2017 Jun 27.

Abstract

Purpose: We report a phase II clinical study of the combination of irinotecan (CPT-11) and pegylated liposomal doxorubicin (PLD) in platinum- and taxane-resistant recurrent ovarian cancer, based on the recommended doses determined in a phase I trial.

Methods: PLD was administered intravenously at a dose of 30 mg/m2 on day 3. CPT-11 was administered intravenously at a dose of 80 mg/m2 on days 1 and 15, according to the recommendations of the phase I study. A single course of chemotherapy lasted 28 days, and patients underwent at least 2 courses until disease progression. The primary endpoint was antitumor efficacy, and the secondary endpoints were adverse events, progression-free survival (PFS), and overall survival (OS).

Results: The response rate was 32.3% and the disease control rate was 64.5%. Grade 3 and 4 neutropenia, anemia, and a decrease in platelet count were observed in 17 (54.9%), 3 (9.7%), and 1 patient (3.2%), respectively. In terms of grade 3 or higher non-hematologic toxicities, grade 3 nausea occurred in 1 patient (3.2%), vomiting in 3 patients (9.7%), and grade 3 diarrhea and fatigue in 1 patient (3.2%). The median PFS and OS rates were 2 months and not reached, respectively. Of the 11 patients with a treatment-free interval (TFI) of ≥3 months, the response rate was 63.3%, and the median PFS was 7 months.

Conclusions: The treatment outcomes for the 31 patients enrolled in this study were unsatisfactory. However, sub-analysis suggested that patients with a TFI of ≥3 months had a good response rate and PFS. This suggests that CPT-11/PLD combination therapy may be a chemotherapy option for platinum-resistant recurrent ovarian cancer.

Keywords: CPT-11; Chemotherapy; PLD; Recurrent ovarian cancer.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Camptothecin / administration & dosage
  • Camptothecin / analogs & derivatives
  • Disease Progression
  • Disease-Free Survival
  • Doxorubicin / administration & dosage
  • Doxorubicin / analogs & derivatives
  • Drug Resistance, Neoplasm*
  • Female
  • Humans
  • Irinotecan
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / pathology
  • Platinum Compounds / administration & dosage
  • Polyethylene Glycols / administration & dosage
  • Survival Rate
  • Taxoids / administration & dosage
  • Treatment Outcome

Substances

  • Platinum Compounds
  • Taxoids
  • liposomal doxorubicin
  • Polyethylene Glycols
  • Irinotecan
  • Doxorubicin
  • Camptothecin