Phase I study of biweekly oxaliplatin, gemcitabine and capecitabine in patients with advanced upper gastrointestinal malignancies.
BACKGROUND
Oxaliplatin, gemcitabine and capecitabine are all active agents against upper gastrointestinal and pancreaticobiliary cancers.


METHODS
Patients with upper gastrointestinal malignancies treated with 0-2 prior chemotherapy regimens received oxaliplatin (85-100 mg/m(2)) as a 2-h i.v. infusion with gemcitabine (800-1000 mg/m(2)) at a constant rate i.v. infusion (CI) of 10 mg/m(2)/min on days 1 and 15 of a 28-day cycle. Capecitabine (600-800 mg/m(2)) was administered orally twice a day on days 1-7 and 15-21. A three per cohort dose escalation schema was used to determine the maximum tolerated dose (MTD) and the dose-limiting toxic effects (DLTs) of this combination regimen.


RESULTS
Thirty patients with advanced upper gastrointestinal malignancies were enrolled. The MTD was defined as oxaliplatin 100 mg/m(2) i.v. over 2 h plus gemcitabine 800 mg/m(2) i.v. at a CI of 10 mg/m(2)/min on days 1 and 15 with capecitabine 800 mg/m(2) p.o. b.i.d. days 1-7 and 15-21 of a 29-day cycle. DLTs include grade 3 fatigue and grade 3 dyspnea. One complete and two partial responses were observed.


CONCLUSIONS
This biweekly schedule of oxaliplatin, gemcitabine and capecitabine is tolerable and warrants further investigation in biliary and pancreatic malignancies.
Tan
B R
BR
Division of Medical Oncology, Washington University School of Medicine, St Louis, MO 63110, USA. btan@im.wustl.edu
Brenner
W S
WS
Picus
J
J
Marsh
S
S
Gao
F
F
Fournier
C
C
Fracasso
P M
PM
James
J
J
Yen-Revollo
J L
JL
McLeod
H L
HL
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D001661:Biliary Tract Neoplasms / Q000188:drug therapy / Q000473:pathology; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000473:pathology; D000093542:Gemcitabine
D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil; D000093542:Gemcitabine