FOLFIRINOX - Oxaliplatin 85 / Folinic Acid 400 / Irinotecan 180 / Fluorouracil 2400, Pancreatic Cancer

Protocol-ID: 47 V1.4 (Standard), FOLFIRINOX (OXAL85/CFOL400/IRIN180/FU2400), Pankreas-Ca

Indication(s)

Pancreatic Cancer; ICD-10 C25.-

Protocol classification

Classification: current standard
Intensity: Standard dose
Therapy mode: First line
Therapy intention: palliative

Cycles

Cycle length 14 days, recommended cycles: 12

Risks

Emetogenicity (MASCC/ESMO): moderate (30-90%)
Neutropenia: very high (>41%) Grade 3 and 4; 42.5% with G-CSF
Febrile Neutropenia: intermediate (10-20%) Grade 3 and 4; 1 death, 42.5% with G-CSF
Thrombocytopenia below 50 000/µl: low (<10%)
Anemia Hb below 8g/dl: moderate (6-15%)
Diarrhea: CTC AE °3-4: 12.7%
Fatigue: CTC AE °3-4: 23.6%
Vomiting: CTC AE °3-4: 14.5%
Thromboembolic Event: CTC AE °3-4: 6.6%
Neuropathy: CTC AE °3-4: 9.0%
Increase Aminotransferases: CTC AE °3-4: 7.3%

Therapy

Day	Substance	Dosage	Appl.	Inf. time	Procedure
HYD Hydration: Balanced Crystalloid Solution
Access: peripheral venous
Hydration before, during, or after antitumor therapy
1	Balanced Crystalloid Solution	500 ml	i.v.	60 min	60 min before Oxaliplatin (d1)

Day	Substance	Dosage	Solution	Appl.	Inf. time	Procedure
AE Antiemesis: Emetogenicity moderate, GRAN i.v., DEXA i.v.
Access: peripheral venous
ASCO 2015, DGHO 2016, DKG 2016, MASCC/ESMO 2016, if palonosetron not available
1	Dexamethasone	8 mg	NaCl 0.9% 50 ml	i.v.	5 min	30 min before Oxaliplatin (d1)
1	Granisetron	1 mg	NaCl 0.9% 50 ml	i.v.	5 min	15 min before Oxaliplatin (d1)
or other 5-HT3 antagonist
2-3	Dexamethasone	8 mg		p.o.		1-0-0-0

Day	Substance	Dosage	Solution	Appl.	Inf. time	Procedure
CTX Antineoplastic therapy: FolFIrinOx
Access: central venous
5-FU, folinic acid, irinotecan, and oxaliplatin in pancreatic cancer
1	Oxaliplatin	85 mg/m² BSA	Dextrose 5% 500 ml	i.v.	2 h	Sequence
1	Folinic acid	400 mg/m² BSA	NaCl 0.9% 250 ml	i.v.	2 h	Sequence
1	Irinotecan	180 mg/m² BSA	NaCl 0.9% 250 ml	i.v.	90 min	90 min before Fluorouracil (d1)
Irinotecan is administered 30 minutes after the start of the folinic acid infusion in parallel with folinic acid.
1	Fluorouracil	400 mg/m² BSA	none	i.v.	1 min	Sequence
Bolus application
1	Fluorouracil	2400 mg/m² BSA	NaCl 0.9% 500 ml	i.v.	46 h	Sequence
The volume of the carrier solution refers to inpatient therapy with infusion pumps. When using syringe pumps or ambulatory systems, a different volume (e.g. 100 ml) can be used.

Day	Substance	Dosage	Appl.	Inf. time	Procedure
HW Hematopoietic growth factors: FN risk 10-20%, G-CSF long-acting, pegylated
Access: - none -
Risk of febrile neutropenia (FN) 10-20% and 1 risk factor: age > 65 y, laboratory parameters (anemia, lymphocytopenia < 700/µl, hypalbuminemia, hyperbilirubinemia) previous chemotherapy, comorbidities, low performance status, advanced symptomatic tumor disease (DKG 2016)
4	Pegfilgrastim	6 mg	subc	Bolus	24 h after Fluorouracil (d1)
Use at risk: FN 10-20% and 1 risk factor, other long-acting G-CSF possible.

Concomitant therapy supplements

If a cholinergic syndrome occurs during Irinotecan, according to the summary of product characteristics, 0.25 mg Atropine sulphate should be administered subcentrally; if a history of cholinergic syndrome is known, Atropine should be administered prophylactically before Irinotecan. Loperamide can be used to treat the onset of delayed diarrhea.

Notes

Increase the risk of febrile neutropenia to medium, as one death due to febrile neutropenia occurred in the study. Filgrastim application was required in 42.5% of patients. For patients with a response, 6 months of therapy was recommended in the literature.

Controls:

Blood count: on day 1 and subsequently weekly
DPD Exclude deficiency: Uracil levels or DPD gene mutations.
Day 1: Anamnesis and clin. examination regarding neuropathy
Day 1: GOT, GPT, GGT, Bilirubin, AP, Cholinesterase Irinotecan: increased risk of toxicity due to decreased hepatic clearance with elevated bilirubin between 1.5 and 3 times the norm, see summary of product characteristics for dose adjustment. Do not administer if bilirubin > 3 times normal elevated. Regular blood count and bilirubin checks in hepatic insufficiency. Fluorouracil: liver monitoring during therapy. Severe hepatic insufficiency is a contraindication.
Day 1: Creatinine, glomerular filtration rate (GFR) Oxaliplatin: no use in patients with severe renal impairment creatinine clearance < 30 ml/min. Irinotecan: no studies on renal insufficiency, use in renal insufficiency is therefore not recommended. Fluorouracil: control of retention values

Original author

Conroy, Thierry (2011)

Origin

Groupe Tumeurs Digestives of Unicancer and the PRODIGE Intergroup

References

Conroy T, FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer.; N Engl J Med 2011 May 12;364(19):1817-25. doi: 10.1056/NEJMoa1011923. PMID: 21561347. [PMID]
Conroy T, Irinotecan Plus Oxaliplatin and Leucovorin-Modulated Fluorouracil in Advanced Pancreatic Cancer, A Groupe Tumeurs Digestives of the Fédération Nationale des Centres de Lutte Contre le Cancer Study; J Clin Oncol 2005 Feb 20;23(6):1228-36. doi: 10.1200/JCO.2005.06.050. PMID: 15718320. [PMID]
Ducreux M, Cancer of the pancreas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2015 Sep;26 Suppl 5:v56-68. doi: 10.1093/annonc/mdv295. PMID: 26314780. [PMID]

Recommendations

11/2023: European Society for Medical Oncology
06/2023: National Comprehensive Cancer Network

Important notice

The copyrighted protocols are treatment recommendations. The information contained in this compilation on cytostatic drugs, concomitant medication and other therapeutic procedures, as well as dosage and application information, is continuously reviewed with all due care by the authors and editors involved. Nevertheless, the publishers and authors do not assume any liability for the correctness - also with regard to possible printing errors.

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