5-fluorouracil plus folinic acid with or without ifosfamide in advanced colorectal cancer: a phase II randomized trial.
OBJECTIVE
This phase II trial evaluated the biomodulation of 5-fluorouracil (5-FU) plus folinic acid (FA) with or without ifosfamide (IFO) in chemotherapy-naive patients with colorectal cancer.


METHODS
Forty-eight patients were randomized to receive: FA (25 mg/m2 iv bolus days 1 to 3), followed by 5-FU (750 mg/m2 iv bolus days 1 to 3), arm A; or FA (25 mg/m2 iv bolus days 1 to 3), followed by 5-FU (750 mg/m2 iv bolus days 1 to 3) plus IFO (2,000 mg/m2 in 1000 mL 5% dextrose in a 2-hr infusion, days 1 to 3), arm B. Mesna was added during and after IFO to prevent hemorrhagic cystitis. Treatment was repeated every 21 days in both arms.


RESULTS
Forty-five patients were assessable for response: in arm A, 5 patients achieved a partial response (overall response, 25%), and in arm B, 2 patients achieved a complete and 1 a partial response (overall response, 12%). Time to failure was 3.5 months (range, 1-38) in patients treated with 5-FU plus FA, and 3 months (range, 1-21) in patients treated with the IFO combination. The median survival time was 13.5 months (range, 1-49 months) in arm A and 16 months (range, 1-43 months) in arm B. Diarrhea, stomatitis and vomiting were the most common nonhematologic toxicities in both arms. The most notable hematologic toxicity was leukopenia; 15% and 20% of patients experienced grade 4 in arm A and arm B, respectively.


CONCLUSIONS
IFO does not increase the activity of the 5-FU plus FA combination in advanced colorectal cancer.
Department of Medicine and Medical Oncology, Santa Maria Hospital, Terni, Italy.
A
A
Sdrobolini
A
A
Contu
B
B
Massidda
S
S
Gasperoni
F
F
Recchia
A
A
Iannelli
S
S
Tomao
A
A
Romiti
M
M
Raffaele
S
S
Ortu
C
C
Campisi
V
V
Gebbia
N
N
Olmeo
M T
MT
Ionta
S
S
Angiona
F
F
Di Costanzo
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016019:Survival Analysis; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D018906:Antineoplastic Agents, Alkylating; D002955:Leucovorin; D005472:Fluorouracil; D007069:Ifosfamide