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

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

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.

Cycles

Cycle length 14 days, recommended cycles: 12

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

Dose adjustment

• Fluorouracil
• for Bone Marrow Insufficiency: Platelets
  >100,000 T./µl- 100% dose; 70000-100000 T./µl- 75% dose; 50000-70000 T./µl- 50% dose; <50000 T/µl STOP!
• for Bone Marrow Insufficiency: Leukocytes
  >4000 L./µl- 100% dose; 3000-4000 L./µl- 75% dose; 2000-3000 L./µl- 50% dose; <2000 L./µl STOP!
• Oxaliplatin
• for Renal Failure: Glomerular Filtration Rate (GFR)
  No data on patients with severe renal impairment (contraindication if creatinine CL < 30ml/min). In moderate renal impairment, close monitoring and dose adjustment according to toxicity. In case of mild renal impairment no dose adjustment necessary
• for Bone Marrow Insufficiency: Neutrophils
  In case of neutrophil count< 1500/µl, the next treatment cycle must be postponed until acceptable values are reached. Before starting oxaliplatin treatment and each new cycle, a complete blood count including differential white blood cell count is required.
• for Bone Marrow Insufficiency: Platelets
  If the platelet count is <50000/µl, the next treatment cycle must be postponed until acceptable values are reached. Prior to initiation of oxaliplatin treatment and each new cycle, a complete blood count including white blood cell differential must be performed.

Original indication

Pancreatic carcinoma (adeno-), metastatic, ECOG 0-1

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, 364:1817-25 [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; , Journal of Clinical Oncology; 23;1228-1236;  [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 [PMID]

Recommendations

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

Status

Valid since 2023-12-05, Version 1.3, last updated 2023-12-05

Last modification: V1.3: Correction title, correction antiemesis V1.2: New Cato import due to cycle counting and diagnosis assignment by ICD-10 codes. V1.1: Cato test done. V1.0: Run times and substance sequence according to primary literature.

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.

The protocols may not be changed in terms of content.

Diagnosis, indication for therapy and treatment of malignant diseases must be carried out in each individual case by the hematologist and oncologist on his or her own responsibility. The treating physician is obligated to this personal responsibility to weigh in each case before a diagnostic or therapeutic measure, indication, contraindications, dosage and application under consideration of the specialized information or other documents of the manufacturers. This applies in particular to rarely used preparations or preparations that are new to the market.

The publishers and authors assume no liability for the accuracy of the contents. The application is at the own responsibility of the treating physician. ©Onkopti.