Phase I study of the gemcitabine/oxaliplatin combination in patients with advanced solid tumors: a preliminary report.
The purpose of this study was to determine the maximum tolerated dose and evaluate the dose-limiting toxicities of the gemcitabine/oxaliplatin combination in patients with advanced-stage solid tumors. Of the 48 enrolled patients, 35% had first-line, 23% had second-line, and 42% had third-line therapy. Patients received escalating doses of 1,000 to 1,600 mg/m2 gemcitabine on days I and 8 plus 60 to 120 mg/m2 oxaliplatin on day 8, every 21 days. The dose-limiting toxicities (first nine dose levels) were grade 4 neutropenia, grade 3 asthenia, and grade I to 3 neutropenia or thrombocytopenia. One hundred fifty-three cycles have been administered without any febrile neutropenia or toxic death. Grade 3-4 neutropenia and grade 3 thrombocytopenia were noted in 13 (9%) and seven (5%) cycles, respectively. Nonhematologic toxicity has been mild; the most common was grade 2 to 3 asthenia occurring in 29% of cycles. Among 30 evaluable patients, four partial responses have been observed (response rate, 13%). In this phase I study, the maximum tolerated dose of this drug combination has not yet been reached, although gemcitabine up to 1,600 mg/m2 (days I and 8) plus oxaliplatin up to 120 mg/m2 (day 8) was active and well tolerated, warranting further evaluation in phase II studies.
Mavroudis
D
D
Department of Medical Oncology, University General Hospital of Heraklion, Crete, Greece.
Kourousis
C
C
Kakolyris
S
S
Agelaki
S
S
Kalbakis
K
K
Androulakis
N
N
Souglakos
J
J
Vardakis
N
N
Samonis
G
G
Georgoulias
V
V
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D016879:Salvage Therapy; D000093542:Gemcitabine
D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000093542:Gemcitabine