Gemcitabine, oxaliplatin and weekly high-dose 5-FU as 24-h infusion in chemonaive patients with advanced or metastatic pancreatic adenocarcinoma: a multicenter phase II trial of the Arbeitsgemeinschaft Internistische Onkologie (AIO).
BACKGROUND
Combinations of gemcitabine-oxaliplatin, gemcitabine-5-fluorouracil (5-FU) and 5-FU-oxaliplatin have synergistic activity and nonoverlapping adverse effect profiles. This trial assessed efficacy and safety of the triple combination gemcitabine-oxaliplatin and infusional 5-FU in patients with locally advanced (n=11) or metastatic (n=32) pancreatic adenocarcinoma.


METHODS
A total of 43 eligible patients were treated with intravenous infusions of gemcitabine (900 mg/m2 over 30 min), followed by oxaliplatin (65 mg/m2 over 2 h) and 5-FU (1500 mg/m2 over 24 h) on days 1 and 8 of a 21-day cycle.


RESULTS
Among all 43 patients, the tumor response rate was 19% [95% confidence interval 7% to 30%]. Nine patients were nonassessable for response because they did not complete the first two cycles of chemotherapy due to rapid disease progression, early death or treatment refusal. One patient was lost to follow-up. Median time to progression and overall survival were 5.7 and 7.5 months. Principal grade III/IV toxic effects were leucopenia in 11 (2%), thrombocytopenia in 13 (2%), nausea in 13 (0%), anorexia 16 (7%) and sensory neuropathy in 18 (0%) of patients. Unexpected cardiotoxicity was observed in this trial.


CONCLUSIONS
Response rates and survival of the three-drug combination compare favorably with single-agent gemcitabine, but do not exceed results for doublets.
Wagner
A D
AD
First Department of Medicine, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany. Electronic address: anna-dorothea.wagner@gmx.de.
Buechner-Steudel
P
P
First Department of Medicine, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany.
Wein
A
A
First Department of Medicine, Friedrich-Alexander-University Erlangen, Erlangen, Germany.
Schmalenberg
H
H
Department of Medicine II, Friedrich-Schiller-University, Jena, Germany.
Lindig
U
U
Department of Medicine II, Friedrich-Schiller-University, Jena, Germany.
Moehler
M
M
First Department of Medicine, Johannes-Gutenberg-University Mainz, Mainz, Germany.
Behrens
R
R
Gastroenterology Practice, Halle (Saale), Germany.
Kleber
G
G
First Department of Medicine, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany.
Kuss
O
O
Institute of Medical Epidemiology, Biostatistics and Informatics, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany.
Fleig
W E
WE
First Department of Medicine, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany.
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011788:Quality of Life; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome; D000093542:Gemcitabine
D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D005472:Fluorouracil; D000093542:Gemcitabine