A phase I study of an oral simulated FOLFOX with high dose capecitabine. Invest New Drugs 2009 Oct;27(5):461-8
Date
01/09/2009Pubmed ID
19129971Pubmed Central ID
PMC2899673DOI
10.1007/s10637-008-9210-8Scopus ID
2-s2.0-70349235532 (requires institutional sign-in at Scopus site) 7 CitationsAbstract
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.
CONCLUSION: 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.
Author List
Mulkerin D, LoConte NK, Holen KD, Thomas JP, Alberti D, Marnocha R, Kolesar J, Eickhoff J, Oliver K, Feierabend C, Wilding GAuthor
James P. Thomas MD, PhD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Administration, OralAdult
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols
Capecitabine
Deoxycytidine
Dose-Response Relationship, Drug
Female
Fluorouracil
Humans
Leucovorin
Male
Maximum Tolerated Dose
Middle Aged
Neoplasm Staging
Neoplasms
Organoplatinum Compounds
Prognosis
Tissue Distribution
Treatment Outcome
