Combining gemcitabine, oxaliplatin and capecitabine (GEMOXEL) for patients with advanced pancreatic carcinoma (APC): a phase I/II trial.
BACKGROUND
Gemcitabine remains the mainstay of palliative treatment of advanced pancreatic carcinoma (APC). Adding capecitabine or a platinum derivative each significantly prolonged survival in recent meta-analyses. The purpose of this study was to determine dose, safety and preliminary efficacy of a first-line regimen combining all three classes of active cytotoxic drugs in APC.


METHODS
Chemotherapy-naive patients with locally advanced or metastatic, histologically proven adenocarcinoma of the pancreas were treated with a 21-day regimen of gemcitabine [1000 mg/m² day (d) 1, d8], escalating doses of oxaliplatin (80-130 mg/m² d1) and capecitabine (650-800 mg/m² b.i.d. d1-d14). The recommended dose (RD), determined in the phase I part of the study by interpatient dose escalation in cohorts of three to six patients, was further studied in a two-stage phase II part with the primary end point of response rate by RECIST criteria.


RESULTS
Forty-five patients were treated with a total of 203 treatment cycles. Thrombocytopenia and diarrhea were the toxic effects limiting the dose to an RD of gemcitabine 1000 mg/m² d1, d8; oxaliplatin 130 mg/m² d1 and capecitabine 650 mg/m² b.i.d. d1-14. Central independent radiological review showed partial remissions in 41% [95% confidence interval (CI) 26% to 56%] of patients and disease stabilization in 37% (95% CI 22% to 52%) of patients.


CONCLUSIONS
This triple combination is feasible and, by far, met the predefined efficacy criteria warranting further investigations.
Hess
V
V
Departments of Medical Oncology. Electronic address: vhess@uhbs.ch.
Pratsch
S
S
Departments of Medical Oncology.
Potthast
S
S
Departments of Radiology, University Hospital Basel.
Lee
L
L
Departments of Medical Oncology.
Winterhalder
R
R
Department of Medical Oncology, Cantonal Hospital Lucerne.
Widmer
L
L
Onkozentrum Hirslanden, Zurich.
Cescato
C
C
Department of Medical Oncology, St Clara Hospital Basel.
Lohri
A
A
Department of Medical Oncology, Cantonal Hospital Liestal.
Jost
L
L
Department of Medical Oncology, Cantonal Hospital Bruderholz.
Stillhart
P
P
Departments of Medical Oncology.
Pestalozzi
B
B
Department of Medical Oncology, University Hospital Zurich, Switzerland.
Herrmann
R
R
Departments of Medical Oncology.
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D000077150:Oxaliplatin; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis; D016896:Treatment Outcome; D000093542:Gemcitabine
D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil; D000093542:Gemcitabine