Phase I Dose-Escalation Trial of an Innovative Chemotherapy Regimen Combining a Fractionated Dose of Irinotecan Plus Bevacizumab, Oxaliplatin, 5-Fluorouracil, and Folinic Acid (bFOLFIRINOX-3) in Chemorefractory Metastatic Colorectal Cancer
The care of metastatic colorectal cancers is based on combination chemotherapies including 5-fluorouracil, oxaliplatin, irinotecan, and monoclonal antibodies targeting the epidermal growth factor receptor or vascular endothelial growth factor. The regimen is determined based on the patient’s molecul...
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2021
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oai:doaj.org-article:8925284c64c64aa89355bb16026e41372021-11-11T15:33:36ZPhase I Dose-Escalation Trial of an Innovative Chemotherapy Regimen Combining a Fractionated Dose of Irinotecan Plus Bevacizumab, Oxaliplatin, 5-Fluorouracil, and Folinic Acid (bFOLFIRINOX-3) in Chemorefractory Metastatic Colorectal Cancer10.3390/cancers132154722072-6694https://doaj.org/article/8925284c64c64aa89355bb16026e41372021-10-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/21/5472https://doaj.org/toc/2072-6694The care of metastatic colorectal cancers is based on combination chemotherapies including 5-fluorouracil, oxaliplatin, irinotecan, and monoclonal antibodies targeting the epidermal growth factor receptor or vascular endothelial growth factor. The regimen is determined based on the patient’s molecular biology and general condition. Irinotecan bifractionation showed efficacy in chemorefractory patients in a previous study, FOLFIRI-3, but a desynchronized triplet has never been tested. The aim of bFOLFIRINOX-3 is to determine the safety, tolerance, and efficacy of a new regimen (FOLFIRINOX-3 bevacizumab) in chemorefractory patients. The aim of this study was to evaluate the safety and efficacy of FOLFIRINOX-3 bevacizumab in chemorefractory metastatic colorectal cancer (mCRC). A standard phase I, “3 + 3” design study was performed. The standard protocol comprised simplified FOLFOX 4 (folinic acid 400 mg/m<sup>2</sup>), 5-fluorouracil (a 400 mg/m<sup>2</sup> bolus followed by 2400 mg/m<sup>2</sup> for 46 h), oxaliplatin (85 mg/m<sup>2</sup>) and irinotecan (administered before and after 5-fluorouracil infusion), plus bevacizumab (5 mg/kg). In a “3 + 3” design, three different doses of irinotecan were tested: 60, 70 and 90 mg/m<sup>2</sup>. The primary endpoint was the maximum tolerable dose (MTD) of irinotecan. The secondary endpoints included the objective response (at 8 and 16 weeks) according to the RECIST 1.1 criteria and progression free survival. Thirteen patients were enrolled, and twelve patients were finally evaluated for dose-limiting toxicity (DLT). The dose level defined was 70 mg/m<sup>2</sup> irinotecan. A total of three DLTs were observed (grade 3 diarrhea): two DLTs at the 90 mg/m<sup>2</sup> dose level and one at the 70 mg/m<sup>2</sup> dose level. The most frequently described adverse events were asthenia (93%), diarrhea (77%), nausea (62%) and peripheral sensory neuropathy (46%). The most frequent biological event was thrombopenia (54%). Regarding efficacy, among the 11 evaluable patients, no progression was observed at 8 weeks, and the partial response rate was 18.2%. At 16 weeks, a partial response rate of 27.3% was observed, and five patients had a stable disease. The new regimen of bFOLFIRINOX-3 with irinotecan at 70 mg/m<sup>2</sup> was well tolerated. In chemorefractory patients, this protocol shows a high response rate.Hélène BellioAurélie BertautAlice HervieuSylvie ZanettaAudrey HennequinJulie VincentRémi PalmierLeila Bengrine-LefevreFrançois GhiringhelliJean-David FumetMDPI AGarticle5-fluorouracilirinotecanoxaliplatinbevacizumabchemotherapy metastatic colorectal cancerNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5472, p 5472 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
5-fluorouracil irinotecan oxaliplatin bevacizumab chemotherapy metastatic colorectal cancer Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 |
| spellingShingle |
5-fluorouracil irinotecan oxaliplatin bevacizumab chemotherapy metastatic colorectal cancer Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Hélène Bellio Aurélie Bertaut Alice Hervieu Sylvie Zanetta Audrey Hennequin Julie Vincent Rémi Palmier Leila Bengrine-Lefevre François Ghiringhelli Jean-David Fumet Phase I Dose-Escalation Trial of an Innovative Chemotherapy Regimen Combining a Fractionated Dose of Irinotecan Plus Bevacizumab, Oxaliplatin, 5-Fluorouracil, and Folinic Acid (bFOLFIRINOX-3) in Chemorefractory Metastatic Colorectal Cancer |
| description |
The care of metastatic colorectal cancers is based on combination chemotherapies including 5-fluorouracil, oxaliplatin, irinotecan, and monoclonal antibodies targeting the epidermal growth factor receptor or vascular endothelial growth factor. The regimen is determined based on the patient’s molecular biology and general condition. Irinotecan bifractionation showed efficacy in chemorefractory patients in a previous study, FOLFIRI-3, but a desynchronized triplet has never been tested. The aim of bFOLFIRINOX-3 is to determine the safety, tolerance, and efficacy of a new regimen (FOLFIRINOX-3 bevacizumab) in chemorefractory patients. The aim of this study was to evaluate the safety and efficacy of FOLFIRINOX-3 bevacizumab in chemorefractory metastatic colorectal cancer (mCRC). A standard phase I, “3 + 3” design study was performed. The standard protocol comprised simplified FOLFOX 4 (folinic acid 400 mg/m<sup>2</sup>), 5-fluorouracil (a 400 mg/m<sup>2</sup> bolus followed by 2400 mg/m<sup>2</sup> for 46 h), oxaliplatin (85 mg/m<sup>2</sup>) and irinotecan (administered before and after 5-fluorouracil infusion), plus bevacizumab (5 mg/kg). In a “3 + 3” design, three different doses of irinotecan were tested: 60, 70 and 90 mg/m<sup>2</sup>. The primary endpoint was the maximum tolerable dose (MTD) of irinotecan. The secondary endpoints included the objective response (at 8 and 16 weeks) according to the RECIST 1.1 criteria and progression free survival. Thirteen patients were enrolled, and twelve patients were finally evaluated for dose-limiting toxicity (DLT). The dose level defined was 70 mg/m<sup>2</sup> irinotecan. A total of three DLTs were observed (grade 3 diarrhea): two DLTs at the 90 mg/m<sup>2</sup> dose level and one at the 70 mg/m<sup>2</sup> dose level. The most frequently described adverse events were asthenia (93%), diarrhea (77%), nausea (62%) and peripheral sensory neuropathy (46%). The most frequent biological event was thrombopenia (54%). Regarding efficacy, among the 11 evaluable patients, no progression was observed at 8 weeks, and the partial response rate was 18.2%. At 16 weeks, a partial response rate of 27.3% was observed, and five patients had a stable disease. The new regimen of bFOLFIRINOX-3 with irinotecan at 70 mg/m<sup>2</sup> was well tolerated. In chemorefractory patients, this protocol shows a high response rate. |
| format |
article |
| author |
Hélène Bellio Aurélie Bertaut Alice Hervieu Sylvie Zanetta Audrey Hennequin Julie Vincent Rémi Palmier Leila Bengrine-Lefevre François Ghiringhelli Jean-David Fumet |
| author_facet |
Hélène Bellio Aurélie Bertaut Alice Hervieu Sylvie Zanetta Audrey Hennequin Julie Vincent Rémi Palmier Leila Bengrine-Lefevre François Ghiringhelli Jean-David Fumet |
| author_sort |
Hélène Bellio |
| title |
Phase I Dose-Escalation Trial of an Innovative Chemotherapy Regimen Combining a Fractionated Dose of Irinotecan Plus Bevacizumab, Oxaliplatin, 5-Fluorouracil, and Folinic Acid (bFOLFIRINOX-3) in Chemorefractory Metastatic Colorectal Cancer |
| title_short |
Phase I Dose-Escalation Trial of an Innovative Chemotherapy Regimen Combining a Fractionated Dose of Irinotecan Plus Bevacizumab, Oxaliplatin, 5-Fluorouracil, and Folinic Acid (bFOLFIRINOX-3) in Chemorefractory Metastatic Colorectal Cancer |
| title_full |
Phase I Dose-Escalation Trial of an Innovative Chemotherapy Regimen Combining a Fractionated Dose of Irinotecan Plus Bevacizumab, Oxaliplatin, 5-Fluorouracil, and Folinic Acid (bFOLFIRINOX-3) in Chemorefractory Metastatic Colorectal Cancer |
| title_fullStr |
Phase I Dose-Escalation Trial of an Innovative Chemotherapy Regimen Combining a Fractionated Dose of Irinotecan Plus Bevacizumab, Oxaliplatin, 5-Fluorouracil, and Folinic Acid (bFOLFIRINOX-3) in Chemorefractory Metastatic Colorectal Cancer |
| title_full_unstemmed |
Phase I Dose-Escalation Trial of an Innovative Chemotherapy Regimen Combining a Fractionated Dose of Irinotecan Plus Bevacizumab, Oxaliplatin, 5-Fluorouracil, and Folinic Acid (bFOLFIRINOX-3) in Chemorefractory Metastatic Colorectal Cancer |
| title_sort |
phase i dose-escalation trial of an innovative chemotherapy regimen combining a fractionated dose of irinotecan plus bevacizumab, oxaliplatin, 5-fluorouracil, and folinic acid (bfolfirinox-3) in chemorefractory metastatic colorectal cancer |
| publisher |
MDPI AG |
| publishDate |
2021 |
| url |
https://doaj.org/article/8925284c64c64aa89355bb16026e4137 |
| work_keys_str_mv |
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