A phase I study of an oral simulated FOLFOX with high dose capecitabine.
BACKGROUND
A phase I study of high-dose capecitabine given over 2 days, along with oxaliplatin, bolus 5FU and leucovorin (LV), was designed to simulate FOLFOX6 without the need for infusional 5FU.


METHODS
Schedule A included oxaliplatin 100 mg/m(2), 5FU 400 mg/m(2), and LV 20 mg/m(2) (all given IV on days 1 and 15, 28 day cycle). Capecitabine was administered orally every 8 h x 6 doses, days 1 and 15. Schedule B excluded 5FU and LV, maintaining oxaliplatin and capecitabine. Pharmacokinetics were performed for capecitabine for 6 patients on each schedule.


RESULTS
36 patients were treated. The dose-limiting toxicities seen included nausea, dehydration, fatigue, hypotension and confusion. Minimal palmar-plantar erythrodysesthesia was seen. Myelosuppression was common, but not a dose limiting toxicity. The pharmacokinetic parameters for capecitabine were unaltered.


CONCLUSIONS
Using capecitabine to mimic FOLFOX6 is feasible and well tolerated with a toxicity profile that differs from standard 14-day capecitabine dosing, with less palmar-plantar erythrodysesthesia. The phase II dose for capecitabine in combination with oxaliplatin, 5FU, and LV is 1,500 mg/m(2)/dose or 2,250 mg/m(2)/dose in the absence of bolus 5FU/LV.
Mulkerin
D
D
University of Wisconsin Paul P Carbone Comprehensive Cancer Center, Madison, WI, USA.
LoConte
N K
NK
Holen
K D
KD
Thomas
J P
JP
Alberti
D
D
Marnocha
R
R
Kolesar
J
J
Eickhoff
J
J
Oliver
K
K
Feierabend
C
C
Wilding
G
G
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000493:pharmacokinetics; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics; D011379:Prognosis; D014018:Tissue Distribution; D016896:Treatment Outcome
D009944:Organoplatinum Compounds; D003841:Deoxycytidine; D000069287:Capecitabine; D002955:Leucovorin; D005472:Fluorouracil