A dose escalation and pharmacokinetic study of biweekly pegylated liposomal doxorubicin, paclitaxel and gemcitabine in patients with advanced solid tumours.
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.
Bozionelou
V
V
Department of Medical Oncology, University General Hospital of Heraklion, Crete, Greece.
Vamvakas
L
L
Pappas
P
P
Agelaki
S
S
Androulakis
N
N
Kalykaki
A
A
Nikolaidou
M
M
Kentepozidis
N
N
Giassas
S
S
Marselos
M
M
Georgoulias
V
V
Mavroudis
D
D
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D009503:Neutropenia / Q000139:chemically induced; D017239:Paclitaxel / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000494:pharmacology; D015996:Survival Rate; D000093542:Gemcitabine
C506643:liposomal doxorubicin; D003841:Deoxycytidine; D011092:Polyethylene Glycols; D004317:Doxorubicin; D017239:Paclitaxel; D000093542:Gemcitabine