Download Gemcitabine

FOLFIRINOX versus Gemcitabine
for Metastatic Pancreatic Cancer
N Engl J Med 2011;364:1817-25.
R3 Ye-Ri So / Prof. Seok-Ho Dong
BACKGROUND
Pancreatic adenocarcinoma:
- 4TH leading cause of death from cancer in the US in 2010
- grim prognosis: 5yr survival rate is 6% in Europe and the US
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Gemcitabine: reference regimen for advanced pancreatic cancer
as compared with fluorouracil (5.6 vs. 4.4 months, P = 0.002)
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The combination of gemcitabine with a variety of cytotoxic and targeted
agents: generally shown no significant survival advantage as compared
with gemcitabine alone.
Some studies have suggested a significant benefit associated with
gemcitabine based cytotoxic combinations in patients with good
performance status.
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Irinotecan: against advanced pancreatic cancer.
synergistic activity when administered before Fluorouracil and Leucovorin.
Oxaliplatin: against pancreatic cancer only when combined with
Fluorouracil.
Oxaliplatin and Irinotecan: synergistic activity
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Phase 1 trial: regimen combining “fluorouracil, leucovorin, irinotecan, and
oxaliplatin” showed responses in advanced pancreatic cancer.
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Phase 2 study: FOLFIRINOX regimen (fluorouracil, leucovorin, irinotecan,
and oxaliplatin) involving 46 patients with good performance status
→ associated with encouraging efficacy and grade 3 or 4 neutropenia in
half the patients.
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Phase 2-3 trial: FOLFIRINOX compared with single agent gemcitabine
as first-line treatment in patients with metastatic pancreatic cancer.
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METHODS
Patients
Inclusion criteria

age of 18 yrs or older
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age of 76 yrs or older
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histologically and cytologically
confirmed, measurable metastatic
pancreatic adenocarcinoma
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endocrine or acinar pancreatic
carcinoma
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previous radiotherapy for measurable
lesions
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cerebral metastases
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history of another major cancer
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active infection
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chronic diarrhea

clinically significant history of cardiac
disease
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pregnancy or breast-feeding
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had not previously been treated with
chemotherapy
ECOG performance status score of 0
or 1
adequate bone marrow
- granulocyte count, ≥1500
- platelet count, ≥100,000
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adequate liver function
- bilirubin ≤1.5 times the upper limit
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Exclusion criteria
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adequate renal function
Study Design and Oversight
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multicenter, randomized, phase 2–3 trial
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Patients were randomly assigned to receive FOLFIRINOX or gemcitabine
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Randomization was performed centrally in a 1:1 ratio with stratification according to
center, performance status (0 vs. 1), and primary tumor localization (the head vs. the
body or tail of the pancreas).
Treatment
Gemcitabine:
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at a dose of 1000 mg/m² of BSA, 30-minute iv infusion weekly for 7 weeks,
followed by a 1-week rest, then weekly for 3 weeks in subsequent 4-week courses.
FOLFIRINOX:
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oxaliplatin at a dose of 85 mg/m², 2 hr iv infusion,
immediately followed by leucovorin at a dose of 400 mg/m², 2 hr iv infusion,
after 30 minutes, irinotecan at a dose of 180 mg/m², 90 min iv
immediately followed by fluorouracil at a dose of 400/m², iv bolus,
followed by a continuous iv infusion of 2400 mg/m² over 46 hr period every 2 weeks.
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Assessments
At the start of every cycle,
the patient’s status was assessed according to
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his or her medical history,
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complete physical examination by a physician,
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ECOG performance status,
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and complete blood counts and blood chemical tests.
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RESULTS
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Characteristics of the Patients
P = 0.05
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Response to Therapy
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Survival
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Adverse Events
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CONCLUSIONS
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As compared with Gemcitabine,
FOLFIRINOX was associated with a survival advantage
and had increased toxicity.
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FOLFIRINOX is an option for the treatment of
patients with metastatic pancreatic cancer
and good performance status.
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