A phase 1 and pharmacokinetic study of gemcitabine and oxaliplatin in patients with solid tumors.
OBJECTIVE
This dose escalation study aimed to determine the recommended doses, toxicity and pharmacokinetics of oxaliplatin and gemcitabine given on days 1 and 8 every 21 days. This schedule may maximize dose intensity of both drugs with acceptable or reduced toxicity.


METHODS
Eligible patients had solid malignancies, no more than two prior courses of chemotherapy, ECOG performance status 0-2, neurotoxicity < or = NCI-CTC grade 1 and adequate organ function. Dose escalation commenced at oxaliplatin 40 mg/m(2) and gemcitabine 750 mg/m(2), both given on days 1 and 8 every 21 days, and reached oxaliplatin 80 mg/m(2) and gemcitabine 1,500 mg/m(2). The two highest dose levels were each expanded to six patients to gain additional toxicity data.


RESULTS
There were no dose limiting toxicities related to treatment and an MTD was not reached. Five patients (24%) had grade 3 neutropenia, without associated infection, and seven patients (33%) had grade 3/4 thrombocytopenia. Neurotoxicity was mild and no worse than grade 1. Two patients with mesothelioma (10%) had partial responses and 11 patients (52%) had disease stabilization. No pharmacokinetic interaction between oxaliplatin and gemcitabine was detected. Dose intensity was maximal at level 4 (oxaliplatin 70 mg/m(2) and gemcitabine 1,250 mg/m(2)).


CONCLUSIONS
This schedule allows oxaliplatin and gemcitabine to be delivered at the full dose intensity of each drug with excellent tolerability and predictable pharmacokinetics. The recommended doses for phase II studies are oxaliplatin 70 mg/m(2) and gemcitabine 1,250 mg/m(2) on days 1 and 8 every 21 days.
Gan
Hui K
HK
Department of Medical Oncology and Ludwig Institute for Cancer Research, Austin Hospital, Heidelberg, Melbourne, VIC, Australia. huikg@bigpond.net.au
Mitchell
Paul L
PL
Galettis
Peter
P
Davis
Ian D
ID
Cebon
Jonathan
J
de Souza
Paul
P
Links
Matthew
M
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D019540:Area Under Curve; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D000093542:Gemcitabine
D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000093542:Gemcitabine