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Bending the Curve Trial by Trial
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Phase III multicenter randomized trial of oxaliplatin added to chronomodulated fluorouracil-leucovorin as first-line treatment of metastatic colorectal cancer

Phase 3N = 200

Population
Previously untreated metastatic colorectal cancer
Design
Multicentre randomised trial in 15 institutions in four countries. A 5-day course of chronomodulated fluorouracil (700 mg per square metre per day) and leucovorin (300 mg per square metre per day), with peak delivery at 0400 hours, was given with or without oxaliplatin on day 1 (125 mg per square metre as a 6-hour infusion), every 21 days. Response was assessed by extramural review of computed tomography scans.
Arms
  • Chronomodulated fluorouracil-leucovorin (control): Chronomodulated fluorouracil and leucovorin, 5-day course every 21 days
  • Chronomodulated fluorouracil-leucovorin plus oxaliplatin (experimental): Chronomodulated fluorouracil and leucovorin plus oxaliplatin 125 mg per square metre on day 1, every 21 days
People
Giacchetti S
Δ median PFS+2.6 monthsΔ median OS−0.5 months
Show the numbers
Results reported for Phase III multicenter randomized trial of oxaliplatin added to chronomodulated fluorouracil-leucovorin as first-line treatment of metastatic colorectal cancer
EndpointAnalysisChronomodulated fluorouracil-leucovorin plus oxaliplatinChronomodulated fluorouracil-leucovorinEffect
ORRRandomised patients (analysis population not stated in the abstract)Objective response rate by extramural review (stated aim of the study)primaryGiacchetti 200053% (42–63%)—The control-arm response rate (16%, 95% CI 9% to 24%) is written as 'Sixteen percent' in the abstract. The difference had P<.001 (printed 'P <. 001').
PFSRandomised patients (analysis population not stated in the abstract)primaryGiacchetti 2000median 8.7 monthsmedian 6.1 monthsP=.048The abstract gives ranges, not confidence intervals: 4.1 to 7.4 months without oxaliplatin and 7.4 to 9.2 months with oxaliplatin.
OSRandomised patients (analysis population not stated in the abstract)primaryGiacchetti 2000median 19.4 monthsmedian 19.9 monthsThe abstract reports the medians (19.9 and 19.4 months) without a p value.
Results reported for Phase III multicenter randomized trial of oxaliplatin added to chronomodulated fluorouracil-leucovorin as first-line treatment of metastatic colorectal cancer
EndpointAnalysisChronomodulated fluorouracil-leucovorin plus oxaliplatinChronomodulated fluorouracil-leucovorinEffect
ORRRandomised patients (analysis population not stated in the abstract)Objective response rate by extramural review (stated aim of the study)primaryGiacchetti 200053% (42–63%)—The control-arm response rate (16%, 95% CI 9% to 24%) is written as 'Sixteen percent' in the abstract. The difference had P<.001 (printed 'P <. 001').
PFSRandomised patients (analysis population not stated in the abstract)primaryGiacchetti 2000median 8.7 monthsmedian 6.1 monthsP=.048The abstract gives ranges, not confidence intervals: 4.1 to 7.4 months without oxaliplatin and 7.4 to 9.2 months with oxaliplatin.
OSRandomised patients (analysis population not stated in the abstract)primaryGiacchetti 2000median 19.4 monthsmedian 19.9 monthsThe abstract reports the medians (19.9 and 19.4 months) without a p value.
Illustrative — modelled from reported values, not trial data. PFS, primary.
0%25%50%75%100%05101520Months (modelled)
  • Chronomodulated fluorouracil-leucovorin (control)
  • Chronomodulated fluorouracil-leucovorin plus oxaliplatin (experimental)

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

Data table (modelled values)
MonthsChronomodulated fluorouracil-leucovorinChronomodulated fluorouracil-leucovorin plus oxaliplatin
0100.0%100.0%
556.7%67.1%
1128.7%41.6%
1616.2%27.9%
228.2%17.3%
Illustrative — modelled from reported values, not trial data. OS, primary.
0%25%50%75%100%010203040Months (modelled)
  • Chronomodulated fluorouracil-leucovorin (control)
  • Chronomodulated fluorouracil-leucovorin plus oxaliplatin (experimental)

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

Data table (modelled values)
MonthsChronomodulated fluorouracil-leucovorinChronomodulated fluorouracil-leucovorin plus oxaliplatin
0100.0%100.0%
1265.8%65.1%
2541.9%40.9%
3727.6%26.7%
5017.5%16.8%
Primary publication: Giacchetti S, Perpoint B, Zidani R, Le Bail N, Faggiuolo R, Focan C, et al. Phase III multicenter randomized trial of oxaliplatin added to chronomodulated fluorouracil-leucovorin as first-line treatment of metastatic colorectal cancer. J Clin Oncol. 2000;18(1):136-47. PubMedDOI

Appears in

Sources

  1. Giacchetti S, Perpoint B, Zidani R, Le Bail N, Faggiuolo R, Focan C, et al. Phase III multicenter randomized trial of oxaliplatin added to chronomodulated fluorouracil-leucovorin as first-line treatment of metastatic colorectal cancer. J Clin Oncol. 2000;18(1):136-47.

    PubMedDOI