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FOLFOXIRI in combination with panitumumab as first-line treatment in quadruple wild-type (KRAS, NRAS, HRAS, BRAF) metastatic colorectal cancer patients: a phase II trial by the Gruppo Oncologico Nord Ovest (GONO).
- Source :
-
Annals of oncology : official journal of the European Society for Medical Oncology [Ann Oncol] 2013 Aug; Vol. 24 (8), pp. 2062-7. Date of Electronic Publication: 2013 May 10. - Publication Year :
- 2013
-
Abstract
- Background: The FOLFOXIRI regimen developed by the Gruppo Oncologico Nord Ovest (GONO) demonstrated higher activity and efficacy compared with FOLFIRI in metastatic colorectal cancer (mCRC). Panitumumab is effective in some patients with KRAS codon 12-13 wild-type mCRC. KRAS codon 61, HRAS, NRAS, and BRAF V600E mutations might predict resistance to anti-epidermal growth factor receptor antibodies.<br />Patients and Methods: We conducted a phase II study evaluating the combination of panitumumab (6 mg/kg on day 1) with a slightly modified GONO-FOLFOXIRI (irinotecan 150 mg/m², oxaliplatin 85 mg/m², and folinate 200 mg/m² on day 1, followed by fluorouracil 3000 mg/m² as a 48-h continuous infusion starting on day 1) repeated every 2 weeks as first-line treatment of wild-type KRAS, HRAS, NRAS (codon 12-13-61), and BRAF unresectable mCRC patients. Fluorouracil dose was reduced to 2400 mg/m² after two of the first three patients reported grade 3-4 diarrhoea (in one case with febrile neutropenia). Induction treatment was scheduled for a maximum of 12 cycles, followed by panitumumab ± fluorouracil/folinate maintenance until progression. Primary end point was overall response rate (ORR).<br />Results: Eighty-seven patients were screened and 37 were enrolled. Thirty-three patients achieved an objective response (ORR: 89%; 95% CI 75% to 96%). Sixteen patients (43%) underwent secondary surgery of metastases, and R0 resection was achieved in 13 cases (35%). At a median follow-up of 17.7 months, median progression-free survival was 11.3 months (95% CI 9.7-12.9 months). After amendment, most common grade 3-4 adverse events reported during induction treatment were neutropenia (48%; febrile neutropenia: 5%), diarrhoea (35%), asthenia (27%), stomatitis (14%), and skin toxic effect (14%). One treatment-related death was registered.<br />Conclusions: Adding panitumumab to FOLFOXIRI is feasible decreasing the dose of fluorouracil and irinotecan to reduce the risk of diarrhoea. Activity and secondary resectability of metastases among Ras-BRAF wild-type patients are promising.
- Subjects :
- Adult
Aged
Antibodies, Monoclonal adverse effects
Camptothecin adverse effects
Camptothecin therapeutic use
Colorectal Neoplasms surgery
Disease-Free Survival
ErbB Receptors immunology
Female
Fluorouracil adverse effects
Fluorouracil therapeutic use
GTP Phosphohydrolases genetics
Humans
Leucovorin adverse effects
Leucovorin therapeutic use
Male
Membrane Proteins genetics
Middle Aged
Organoplatinum Compounds adverse effects
Organoplatinum Compounds therapeutic use
Panitumumab
Proto-Oncogene Proteins genetics
Proto-Oncogene Proteins B-raf genetics
Proto-Oncogene Proteins p21(ras) genetics
Treatment Outcome
ras Proteins genetics
Antibodies, Monoclonal therapeutic use
Antineoplastic Combined Chemotherapy Protocols adverse effects
Antineoplastic Combined Chemotherapy Protocols therapeutic use
Camptothecin analogs & derivatives
Colorectal Neoplasms drug therapy
Neoplasm Metastasis drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1569-8041
- Volume :
- 24
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Annals of oncology : official journal of the European Society for Medical Oncology
- Publication Type :
- Academic Journal
- Accession number :
- 23666916
- Full Text :
- https://doi.org/10.1093/annonc/mdt165