Pegylated liposomal doxorubicin and carboplatin in advanced gynecologic tumors: a prospective phase I/II study of the Arbeitsgemeinschaft Gynaekologische Onkologie Studiengruppe Ovarialkarzinom (AGO-OVAR)

Ann Oncol. 2006 Jan;17(1):93-6. doi: 10.1093/annonc/mdj032. Epub 2005 Nov 9.

Abstract

Background: Single-agent platinum and single-agent pegylated liposomal doxorubicin (PLD) are both effective in the treatment of gynecologic malignancies. Based on evidence that combination platinum-containing regimens offer superior efficacy versus single-agent regimens, we conducted this study to determine the maximum tolerated dose (MTD) of PLD in combination with carboplatin.

Patients and methods: In this phase I/II dose-finding study, six courses of PLD (20, 30, 40 or 50 mg/m2) and carboplatin (AUC 6) were administered every 28 days to women with advanced gynecologic malignancies. Three to six patients were treated at each dose level; an additional 12 patients were treated at the MTD.

Results: PLD 40 mg/m2 was identified as the MTD when administered with carboplatin. Five of 18 patients experienced a dose-limiting toxicity at the MTD; two patients had grade 3/4 neutropenia, and one each had grade 3 emesis and grade 3 thrombocytopenia and thrombosis. No patient developed cardiotoxicity. In 11 patients evaluable for response, there were two complete responses, two partial responses and four patients with stable disease.

Conclusions: The MTD for PLD when administered in combination with carboplatin is 40 mg/m2. This regimen is well tolerated and offers promising activity in women with advanced gynecologic malignancies.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Area Under Curve
  • Carboplatin / administration & dosage
  • Dose-Response Relationship, Drug
  • Doxorubicin / administration & dosage
  • Doxorubicin / analogs & derivatives
  • Endometrial Neoplasms / drug therapy*
  • Endometrial Neoplasms / mortality
  • Female
  • Humans
  • Maximum Tolerated Dose
  • Middle Aged
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / mortality
  • Polyethylene Glycols / administration & dosage
  • Prospective Studies
  • Sarcoma / drug therapy*
  • Sarcoma / mortality
  • Survival Rate
  • Uterine Cervical Neoplasms / drug therapy*
  • Uterine Cervical Neoplasms / mortality

Substances

  • liposomal doxorubicin
  • Polyethylene Glycols
  • Doxorubicin
  • Carboplatin