title: Overcoming resistance to chronomodulated 5-fluorouracil and folinic acid by the addition of chronomodulated oxaliplatin in advanced colorectal cancer patients.
abstract: The addition of oxaliplatin (L-OHP) to a 5-fluorouracil (5-FU)/ leucovorin (FA) regimen was retrospectively evaluated in 35 consecutive advanced colorectal cancer patients after progression of disease. L-OHP, 25 mg/m2/day, was infused from 10.00-22.00 with a peak flow at 16.00 while 5-FU, 700 mg/m2/day and FA, 150 mg/m2/day of the I-form or 300 mg/m2/day of the racemic form, from 22.00 to 10.00 with a nocturnal peak at 4.00, for 5 days every 3 weeks in 24 patients and for 4 days every 2 weeks in the other 11. Diarrhea and sensitive neuropathy were the most relevant types of toxicity (17% of patients). An objective response was achieved in 8/35 patients (23%) [95% CL 9-37], stabilization in 15 patients (43%) which included five minor responses, and progression in 12. There was no relevant difference in quality of life assessed with the EORTC QLQ C30+3 questionnaire before and after treatment. Median duration of response and median progression-free survival were 6 months; median overall survival was 11 months. This retrospective study showed that it is possible to reverse resistance to chronomodulated 5-FU by adding chronomodulated L-OHP to the previous regimen; comparison with different schedules of this combination should be performed in order to identify the best tolerated and active regimen as second-line treatment of advanced colorectal cancer.
authors.affiliation: Oncologia Medica Complementare, Istituto Regina Elena, Rome, Italy. garufi@sirio-oncology.it
authors.forename: C
authors.initials: C
authors.lastname: Garufi
authors.forename: S
authors.initials: S
authors.lastname: Brienza
authors.forename: P
authors.initials: P
authors.lastname: Pugliese
authors.forename: A M
authors.initials: AM
authors.lastname: Aschelter
authors.lastname: Bensmaine
authors.forename: F
authors.initials: F
authors.lastname: Bertheault-Cvitkovic
authors.forename: C
authors.initials: C
authors.lastname: Nisticò
authors.forename: S
authors.initials: S
authors.lastname: Giunta
authors.forename: M
authors.initials: M
authors.lastname: Caterino
authors.forename: D
authors.initials: D
authors.lastname: Giannarelli
authors.forename: M
authors.initials: M
authors.lastname: Cosimelli
authors.forename: F
authors.initials: F
authors.lastname: Lévi
authors.forename: E
authors.initials: E
authors.lastname: Terzoli
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000627:therapeutic use; D019454:Chronotherapy; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004351:Drug Resistance; D019008:Drug Resistance, Neoplasm; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000627:therapeutic use; D005500:Follow-Up Studies; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage* / Q000627:therapeutic use; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000627:therapeutic use; D000077150:Oxaliplatin; D011788:Quality of Life; D012189:Retrospective Studies; D011795:Surveys and Questionnaires
chemical_list: D000964:Antimetabolites, Antineoplastic; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D002955:Leucovorin; D005472:Fluorouracil