A dose-escalation and pharmacokinetic study of gemcitabine and oxaliplatin in patients with advanced solid tumors (Journal article)

Mavroudis, D./ Pappas, P./ Kouroussis, C./ Kakolyris, S./ Agelaki, S./ Kalbakis, K./ Androulakis, N./ Souglakos, J./ Vardakis, N./ Nikolaidou, M./ Samonis, G./ Marselos, M./ Georgoulias, V.

BACKGROUND: Gemcitabine and oxaliplatin have broad antineoplastic activity and favorable toxicity. We conducted a phase I study to determine the maximum tolerated doses (MTDs) and dose-limiting toxicities (DLTs) of the combination in patients with advanced solid tumors. PATIENTS AND METHODS: Sixty-eight patients with advanced stage solid tumors were enrolled. Treatment was first-line for 35% of patients, second-line for 27%, and third-line for 38%. Gemcitabine was administered at escalating doses of 1000-2000 mg/m(2) as a 30-min intravenous (i.v.) infusion on days 1 and 8 and oxaliplatin at 60-130 mg/m(2) as a 4-h i.v. infusion on day 8 every 21 days without growth factor support. RESULTS: The MTD was defined at gemcitabine 1800 mg/m(2) on days 1 and 8 and oxaliplatin 130 mg/m(2) on day 8. Twelve dose levels were evaluated and DLTs occurring during the first cycle consisted of grade 4 neutropenia, grade 3 asthenia or mucositis and grade 1-3 neutropenia or thrombocytopenia resulting in treatment delays. A total of 266 cycles were administered with only one episode of febrile neutropenia and no toxic deaths. Seven (3%) and 26 (10%) cycles were complicated by grade 4 and 3 neutropenia, respectively, three (1%) and 13 (5%) by grade 4 and 3 thrombocytopenia, and eight (3%) by grade 3 anemia. The most common non-hematological toxicity was grade 2/3 asthenia observed in 23% of cycles. Responses were observed in patients with a variety of epithelial neoplasms. The pharmacokinetic study revealed no significant interaction between the two drugs. CONCLUSIONS: The combination of gemcitabine and oxaliplatin has excellent tolerability and promising activity in patients with advanced solid tumors. As the MTD exceeds the recommended single-agent dose for gemcitabine, and a dose-response effect has not been established, we recommend using both drugs at full doses, e.g. gemcitabine 1200-1400 mg/m(2) on days 1 and 8 and oxaliplatin 130 mg/m(2) on day 8 for further phase II studies.
Institution and School/Department of submitter: Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής
Keywords: Adult,Aged,Antineoplastic Combined Chemotherapy Protocols/administration & dosage/*adverse,effects/*therapeutic use,Deoxycytidine/administration & dosage/adverse effects/*analogs &,derivatives/pharmacokinetics,Female,Humans,Infusions, Intravenous,Male,Maximum Tolerated Dose,Middle Aged,Neoplasms/drug therapy,Neutropenia/chemically induced,Organoplatinum Compounds/administration & dosage/adverse effects/pharmacokinetics
URI: https://olympias.lib.uoi.gr/jspui/handle/123456789/24354
ISSN: 0923-7534
Link: http://www.ncbi.nlm.nih.gov/pubmed/12562660
Appears in Collections:Άρθρα σε επιστημονικά περιοδικά ( Ανοικτά)

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