A dose-escalation study of pegylated liposomal Doxorubicin and oxaliplatin in patients with advanced solid tumors.
OBJECTIVE
A phase I study was conducted to determine the maximum tolerated doses (MTDs) and dose-limiting toxicities (DLTs) of the pegylated liposomal doxorubicin (PLD) and oxaliplatin combination in patients with advanced solid tumors.


METHODS
Forty-five patients with advanced-stage solid tumors received escalating doses of PLD 25-50 mg/m(2) as 60-min intravenous (i.v.) infusion and oxaliplatin 80-130 mg/m(2) as 2- to 4-hour i.v. infusion on day 1 every 3 weeks without growth factors.


RESULTS
MTD was defined at PLD 45 mg/m(2) and oxaliplatin 130 mg/m(2). Eleven dose levels were evaluated and DLTs were grade 2-3 neutropenia resulting in treatment delays, grade 3 neurotoxicity and nausea/vomiting. A total of 187 cycles were administered with two episodes of febrile neutropenia and one toxic death due to sepsis. Two (4%) and 6 (13%) patients developed grade 4 and 3 neutropenia, respectively, 2 (4%) and 1 (2%) grade 4 and 3 thrombocytopenia, and 1 (2%) grade 4 anemia. The most common nonhematological toxicities were grade 2-3 nausea/vomiting and asthenia observed in 27 (60%) and 16 (36%) of patients, respectively. One complete and eight partial responses were observed.


CONCLUSIONS
The combination of PLD and oxaliplatin has an acceptable toxicity profile with promising activity and merits further evaluation in phase II studies.
Kotsakis
A
A
Department of Medical Oncology, University General Hospital of Heraklion, Heraklion, Crete, Greece.
Kouroussis
Ch
Ch
Androulakis
N
N
Agelaki
S
S
Kalbakis
K
K
Vamvakas
L
L
Vardakis
N
N
Kalykaki
A
A
Polyzos
A
A
Georgoulias
V
V
Mavroudis
D
D
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D000077150:Oxaliplatin; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000009:adverse effects
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; C506643:liposomal doxorubicin; D000077150:Oxaliplatin; D011092:Polyethylene Glycols; D004317:Doxorubicin