A dose escalation and pharmacokinetic study of the biweekly administration of paclitaxel, gemcitabine and oxaliplatin in patients with advanced solid tumors.
OBJECTIVE
To determine the dose-limiting toxicities (DLTs) and the maximum tolerated doses (MTDs) of the paclitaxel, gemcitabine, oxaliplatin combination administered biweekly in patients with advanced solid tumors.


METHODS
Patients received escalated doses of paclitaxel (starting dose: 100 mg/m(2)), gemcitabine (starting dose: 800 mg/m(2)) and oxaliplatin (starting dose: 50 mg/m(2)) on days 1 and 15 in cycles of every 4 weeks. DLTs were evaluated during the first cycle.


RESULTS
Twenty-seven patients (median age 65 years) with performance status 0-1 were treated on six dose escalation levels. Eleven patients (40.7%) were chemotherapy naïve, six (22.2%) had received 1 prior chemotherapy regimen and ten (37.1%) 2 or more. The DLT level was reached at the doses of paclitaxel 110 mg/m(2), gemcitabine 1,150 mg/m(2) and LOHP 70 mg/m(2). The dose-limiting events were grade 4 neutropenia and grade 3 febrile neutropenia. Neutropenia was the most common adverse event. A median of 3 cycles per patient was administered. One complete and five partial responses were observed in patients with ovarian carcinoma, NSCLC, urothelial cancer, mesothelioma and cancer of unknown primary. No pharmacokinetic drug interactions were detected.


CONCLUSIONS
The recommended doses for future phase II studies of this combination are paclitaxel 110 mg/m(2), gemcitabine 1,000 mg/m(2) and oxaliplatin 70 mg/m(2) every 2 weeks. The regimen is generally well tolerated and merits further evaluation.
Department of Medical Oncology, University Hospital of Heraklion, 71110 Heraklion, Crete, Greece.
Zacharenia
Z
Saridaki
Periklis
P
Pappas
John
J
Souglakos
Martha
M
Nikolaidou
Nikolaos
N
Vardakis
Athanasios
A
Kotsakis
Marios
M
Marselos
Vassilis
V
Georgoulias
Dimitris
D
Mavroudis
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; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D005334:Fever / Q000139:chemically induced; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D009503:Neutropenia / Q000139:chemically induced*; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D017239:Paclitaxel / Q000008:administration & dosage; D000093542:Gemcitabine
D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D017239:Paclitaxel; D000093542:Gemcitabine