1. ¹Department of Medical Oncology, University General Hospital of Heraklion, Crete, Greece
2. ²Department of Pharmacology, School of Medicine, University of Ioannina, Ioannina, Greece

Correspondence: Dr D Mavroudis, Department of Medical Oncology, University General Hospital of Heraklion, PO Box 1352, 711 10 Heraklion, Crete, Greece. E-mail: mavrudis@med.uoc.gr

Received 13 November 2006; Revised 8 May 2007; Accepted 9 May 2007; Published online 5 June 2007.

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.