A dose escalation and pharmacokinetic study of biweekly pegylated liposomal doxorubicin, paclitaxel and gemcitabine in patients with advanced solid tumours

Br J Cancer. 2007 Jul 2;97(1):43-9. doi: 10.1038/sj.bjc.6603832. Epub 2007 Jun 5.

Abstract

To determine the maximum tolerated doses (MTDs) and dose-limiting toxicities (DLTs) of pegylated liposomal doxorubicin (PLD), paclitaxel (PCX) and gemcitabine (GEM) combination administered biweekly in patients with advanced solid tumours. Twenty-two patients with advanced-stage solid tumours were treated with escalated doses of PLD on day 1 and PCX plus GEM on day 2 (starting doses: 10, 100 and 800 mg m(-2), respectively) every 2 weeks. DLTs and pharmacokinetic (PK) parameters of all drugs were determined during the first cycle of treatment. All but six (73%) patients had previously received at least one chemotherapy regimen. The DLT dose level was reached at PLD 12 mg m(-2), PCX 110 mg m(-2) and GEM 1000 mg m(-2) with neutropaenia being the dose-limiting event. Of the 86 chemotherapy cycles delivered, grade 3 and 4 neutropaenia occurred in 20% with no cases of febrile neutropaenia. Non-haematological toxicities were mild. The recommended MTDs are PLD 12 mg m(-2), PCX 100 mg m(-2) and GEM 1000 mg m(-2) administered every 2 weeks. The PK data revealed no obvious drug interactions. Biweekly administration of PLD, PCX and GEM is a well-tolerated chemotherapy regimen, which merits further evaluation in various types of solid tumours.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / pharmacokinetics
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / pharmacokinetics
  • Doxorubicin / administration & dosage
  • Doxorubicin / analogs & derivatives*
  • Doxorubicin / pharmacology
  • Female
  • Gemcitabine
  • Humans
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Neoplasms / drug therapy*
  • Neutropenia / chemically induced
  • Paclitaxel / administration & dosage*
  • Paclitaxel / pharmacokinetics
  • Polyethylene Glycols / administration & dosage*
  • Polyethylene Glycols / pharmacology
  • Survival Rate

Substances

  • liposomal doxorubicin
  • Deoxycytidine
  • Polyethylene Glycols
  • Doxorubicin
  • Paclitaxel
  • Gemcitabine