A phase I study of pegylated liposomal doxorubicin and irinotecan in patients with solid tumors

Chemotherapy. 2009;55(6):441-5. doi: 10.1159/000264925. Epub 2009 Dec 8.

Abstract

Background: Preclinical studies have shown synergism between topoisomerase I and II inhibitors.

Methods: We conducted a phase I study evaluating the combination of pegylated liposomal doxorubicin and irinotecan in patients with previously treated solid tumors.

Results: Twelve patients were enrolled. The median age was 62 years (range 19-72). The most common grade 3/4 toxicities were neutropenia (dose-limiting toxicity), diarrhea and nausea/vomiting. The maximal tolerated dose and recommended schedule were pegylated liposomal doxorubicin 20 mg/m(2) over 60 min on day 1, followed by irinotecan 100 mg/m(2) over 90 min on days 1 and 8 of a 21-day cycle. There were no objective clinical responses, but 5 patients achieved stable disease lasting a median of 11 weeks duration (range 2-35).

Conclusions: This regimen should be further studied in patients with tumors known to have a sensitivity to both topoisomerase I and II inhibitors such as ovarian and small cell carcinoma.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Camptothecin / administration & dosage
  • Camptothecin / analogs & derivatives
  • Dose-Response Relationship, Drug
  • Doxorubicin / administration & dosage
  • Doxorubicin / analogs & derivatives
  • Drug Administration Schedule
  • Female
  • Humans
  • Irinotecan
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Polyethylene Glycols / administration & dosage
  • Topoisomerase I Inhibitors
  • Topoisomerase II Inhibitors
  • Treatment Outcome
  • Young Adult

Substances

  • Topoisomerase I Inhibitors
  • Topoisomerase II Inhibitors
  • liposomal doxorubicin
  • Polyethylene Glycols
  • Irinotecan
  • Doxorubicin
  • Camptothecin