The role of 5-fluorouracil (5-FU) reintroduction with irinotecan or oxaliplatin in truly 5-FU-refractory advanced colorectal cancer patients.
OBJECTIVE
Although several evidences have demonstrated a synergistic activity of 5-fluorouracil with irinotecan and oxaliplatin, thus explaining the use of this drug combination in the first-line treatment of advanced colorectal cancer, the need for the reintroduction of 5-FU in the second-line setting is more questionable.


METHODS
We retrospectively evaluated the outcome of patients developing progressive disease while on an infusional 5-FU-based front-line chemotherapy and subsequently treated with one of the four following chemotherapy regimens: irinotecan, oxaliplatin and irinotecan or oxaliplatin both combined with the de Gramont schedule (LV5-FU2).


RESULTS
225 patients (137 males and 88 females), were eligible for analysis. Second-line chemotherapy consisted of irinotecan in 79 patients (35%, group A), oxaliplatin in 47 patients (21%, group B), irinotecan with LV5-FU2 in 53 patients (24%, group C) and oxaliplatin with LV5-FU2 in the remaining 46 cases (20%, group D). The response rate to second-line chemotherapy was obtained in 6/79 patients (8%) in group A, in 4/47 patients (9%) in group B, in 11/53 patients (21%) in group C and in 10/46 patients (22%) in group D (p = 0.04).


CONCLUSIONS
These data suggest that reintroduction of 5-FU could increase irinotecan and oxaliplatin activity in patients progressing during a 5-FU-based first-line chemotherapy.
Scartozzi
M
M
Clinica di Oncologia Medica, Azienda Ospedaliera Umberto I-Università Politecnica delle Marche, Ancona, Italy.
Sobrero
A
A
Gasparini
G
G
Berardi
R
R
Catalano
V
V
Graziano
F
F
Barni
S
S
Zaniboni
A
A
Beretta
G D
GD
Labianca
R
R
Cascinu
S
S
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage*; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D012189:Retrospective Studies; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin