Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer: trial

Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer

Phase 3N = 420

Population

Previously untreated advanced colorectal cancer with measurable disease

Design

Randomised phase 3 trial: a 2-hour infusion of leucovorin (200 mg per square metre per day) followed by a fluorouracil bolus (400 mg per square metre per day) and a 22-hour infusion (600 mg per square metre per day) for two consecutive days every 2 weeks (LV5FU2), alone or together with oxaliplatin 85 mg per square metre as a 2-hour infusion on day 1. The primary endpoint was progression-free survival.

Primary endpoint

PFS

Arms

LV5FU2 alone (control): Leucovorin 200 mg per square metre, fluorouracil bolus 400 mg per square metre and 22-hour infusion 600 mg per square metre on two consecutive days every 2 weeks
LV5FU2 plus oxaliplatin (experimental): LV5FU2 plus oxaliplatin 85 mg per square metre as a 2-hour infusion on day 1

People

de Gramont A

Δ median PFS+2.8 monthsΔ ORR+28.4 pointsΔ median OS+1.5 months

Show the numbers

Results reported for Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer
Endpoint	Analysis	LV5FU2 plus oxaliplatin	LV5FU2 alone	Effect
PFSRandomised patients (analysis population not stated in the abstract)	primaryde 2000	median 9 months	median 6.2 months	P=.0003
ORRRandomised patients (analysis population not stated in the abstract)	primaryde 2000	50.7%	22.3%	P=.0001
OSRandomised patients (analysis population not stated in the abstract)	primaryde 2000	median 16.2 months	median 14.7 months	P = .12 as printed in the abstract (written 'P =. 12'); the authors state the improvement in overall survival did not reach significance.

Results reported for Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer
Endpoint	Analysis	LV5FU2 plus oxaliplatin	LV5FU2 alone	Effect
PFSRandomised patients (analysis population not stated in the abstract)	primaryde 2000	median 9 months	median 6.2 months	P=.0003
ORRRandomised patients (analysis population not stated in the abstract)	primaryde 2000	50.7%	22.3%	P=.0001
OSRandomised patients (analysis population not stated in the abstract)	primaryde 2000	median 16.2 months	median 14.7 months	P = .12 as printed in the abstract (written 'P =. 12'); the authors state the improvement in overall survival did not reach significance.

Illustrative — modelled from reported values, not trial data. PFS, primary.

Show curves

LV5FU2 alone (control)
LV5FU2 plus oxaliplatin (experimental)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)

Months	LV5FU2 alone	LV5FU2 plus oxaliplatin
0	100.0%	100.0%
6	51.1%	63.0%
11	29.2%	42.9%
17	14.9%	27.0%
23	7.6%	17.0%

Illustrative — modelled from reported values, not trial data. OS, primary.

Show curves

LV5FU2 alone (control)
LV5FU2 plus oxaliplatin (experimental)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)

Months	LV5FU2 alone	LV5FU2 plus oxaliplatin
0	100.0%	100.0%
10	62.4%	65.2%
20	38.9%	42.5%
30	24.3%	27.7%
41	14.5%	17.3%

Appears in

2000 Oxaliplatin added to infusional fluorouracil in advanced CRC

Sources

de Gramont A, Figer A, Seymour M, Homerin M, Hmissi A, Cassidy J, et al. Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol. 2000;18(16):2938-47.
PubMed DOI