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FOLFIRI is the other backbone bowel-cancer chemotherapy, swapping oxaliplatin for irinotecan. Used first or second line and, since 2026, with the BRAF combination.
FOLFIRI pairs irinotecan, whose active metabolite SN-38 inhibits topoisomerase I, with 5-FU and leucovorin, which inhibit thymidylate synthase, given as a 46-hour infusion every 14 days. It is one of the two backbone chemotherapies for metastatic colorectal cancer, interchangeable with FOLFOX in first-line efficacy (Tournigand 2004) and the standard second-line switch. It is the partner for cetuximab (CRYSTAL, FIRE-3), bevacizumab, aflibercept, ramucirumab and, since 2026, encorafenib plus cetuximab in BRAF V600E disease (BREAKWATER cohort 3, PFS HR 0.44). Diarrhoea, neutropenia and alopecia are the main toxicities, and UGT1A1*28 homozygotes need irinotecan dose reduction. Whether to start with FOLFIRI or FOLFOX is decided by side-effect preference rather than efficacy. For a newcomer, FOLFIRI is bowel cancer chemotherapy with irinotecan instead of oxaliplatin.
Irinotecan (via SN-38) inhibits topoisomerase I; 5-FU/leucovorin inhibit thymidylate synthase.
1.Irinotecan is converted in the body to SN-38
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| Adverse event |
|---|
| Diarrhoea |
| Neutropenia |
| Alopecia |
Early (cholinergic) and late; can be severe. Events listed without rates were not read from a primary source; see the label. Blank cells mean the figure was not sourced, not that it is zero.
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Encorafenib with cetuximab became the standard second-line treatment for BRAF V600E disease, and the platform BREAKWATER later moved into first line with chemotherapy added, doubling survival again.
The negative counterweight to FIRE-3. The two trials are reconciled only by primary tumour side, which is why the sidedness analysis rather than either trial is what guidelines now cite.
The triplet is the option for fit patients who need a response, particularly in BRAF-mutant and right-sided disease where the EGFR antibody route is closed; it also quantified how much worse BRAF-mutant disease was before BEACON and BREAKWATER.
Together with PARADIGM it makes the EGFR antibody the preferred first partner for chemotherapy in left-sided RAS wild-type disease; the survival gain without a progression-free survival gain remains one of the field's unexplained results.
Biomarker-directed treatment in colorectal cancer starts here: RAS testing became mandatory before an EGFR antibody, and the corpus's updated CRYSTAL analysis (paper-kras-colorectal-j-clin-oncol-2011) carries the mature survival figures in the wild-type group.
Query for this drug: (TITLE:"FOLFIRI" OR ABSTRACT:"FOLFIRI" OR TITLE:"5-FU, leucovorin, irinotecan" OR ABSTRACT:"5-FU, leucovorin, irinotecan") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about FOLFIRI (5-FU, leucovorin, irinotecan), not a curated reading list.
Shares A Study of Novel Study Interventions and Combinations in Participants With Colorectal Cancer, Pegcetacoplan in Combination With Modified FOLFIRINOX for the Treatment of Metastatic Pancreatic Ductal Adenocarcinoma, A Phase Ib/II Clinical Study on AK112 Combined or Not Combined With AK119 in pMMR/MSS Colorectal Cancer, A Study of Amivantamab Monotherapy and in Addition to Standard-of-Care Chemotherapy in Participants With Advanced or Metastatic Colorectal Cancer.
Shares HSK42360-Na Tablets Combined With Cetuximab With or Without Chemotherapy in BRAF V600-Mutant Metastatic Colorectal Cancer, Cetuximab Plus Irinotecan in Patients With NeoRAS Wild-type Metastatic Colorectal Cancer In Third-line Therapy, A Phase II Study of AMT-676 Combination Therapies in Advanced Colorectal Cancer, Anti-EGFR antibody + chemotherapy in left-sided RAS/BRAF wild-type mCRC.
Shares HSK42360-Na Tablets Combined With Cetuximab With or Without Chemotherapy in BRAF V600-Mutant Metastatic Colorectal Cancer, Pegcetacoplan in Combination With Modified FOLFIRINOX for the Treatment of Metastatic Pancreatic Ductal Adenocarcinoma, Second-line Zimberelimab and SIRIOX Chemotherapy for Patient With Previously AG Chemotherapy Treated Pancreatic Cancer, A Phase Ib/II Clinical Study on AK112 Combined or Not Combined With AK119 in pMMR/MSS Colorectal Cancer.
Shares A Study of a Selective T Cell Receptor (TCR) Targeting, Bifunctional Antibody-fusion Molecule STAR0602 in Participants With Advanced Solid Tumors, AZD0901 in Participants With Advanced Solid Tumours Expressing Claudin18.2, A Study of ART0380 for the Treatment of Advanced or Metastatic Solid Tumors, A Clinical Study of Liposomal Irinotecan for Second-Line Therapy in Metastatic Colorectal Cancer.
Shares A Study of Novel Study Interventions and Combinations in Participants With Colorectal Cancer, HSK42360-Na Tablets Combined With Cetuximab With or Without Chemotherapy in BRAF V600-Mutant Metastatic Colorectal Cancer, AZD0901 in Participants With Advanced Solid Tumours Expressing Claudin18.2, A Study of AK112 With or Without AK117 in Metastatic Colorectal Cancer.
Shares LPM6690176 in Combination With Chemotherapy and Bevacizumab in Metastatic Colorectal Cancer Patients With RAS Mutation, AK112 Plus FOLFIRI Versus Bevacizumab Plus FOLFIRI as Second-line Treatment of MSS/pMMR Metastatic Colorectal Cancer, 5FU/LV, Irinotecan, Temozolomide and Bevacizumab for MGMT Silenced, Microsatellite Stable Metastatic Colorectal Cancer., A Clinical Study of Liposomal Irinotecan for Second-Line Therapy in Metastatic Colorectal Cancer.
Shares Pegcetacoplan in Combination With Modified FOLFIRINOX for the Treatment of Metastatic Pancreatic Ductal Adenocarcinoma, A Phase Ib/II Clinical Study on AK112 Combined or Not Combined With AK119 in pMMR/MSS Colorectal Cancer, A Clinical Study of Liposomal Irinotecan for Second-Line Therapy in Metastatic Colorectal Cancer, DCE-MRI for Neoadjuvant Treatment Assessment in Patients With Borderline Resectable Pancreatic Cancer.
Shares ValproIc Acid to Potentiate Anti-EGFR Treatment Efficacy and Prevent/Revert Resistance in Colorectal Cancer, Intermittent or Continuous Panitumumab Plus FOLFIRI for Left Sided RAS/B-RAF Wild-type Metastatic Colorectal Cancer, Anti-EGFR antibody + chemotherapy in left-sided RAS/BRAF wild-type mCRC, Systemic Oxaliplatin or Intra-arterial Chemotherapy Combined With LV5FU2 +/- Irinotecan and an Target Therapy in First Line Treatment of Metastatic Colorectal C.