Adjunction of a fish oil emulsion to cytarabine and daunorubicin induction chemotherapy in high-risk AML
Abstract The treatment of acute myeloid leukemia (AML) with unfavorable cytogenetics treatment remains a challenge. We previously established that ex vivo exposure of AML blasts to eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), or fish oil emulsion (FO) induces Nrf2 pathway activation, met...
| Main Authors: | , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2022-06-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-13626-y |
| _version_ | 1818236869426544640 |
|---|---|
| author | Emmanuel Gyan Arnaud Pigneux Mathilde Hunault Pierre Peterlin Martin Carré Jacques-Olivier Bay Caroline Bonmati Maria-Pilar Gallego-Hernanz Bruno Lioure Philippe Bertrand Nicolas Vallet David Ternant François Darrouzain Frédéric Picou Marie-Christine Béné Christian Récher Olivier Hérault |
| author_facet | Emmanuel Gyan Arnaud Pigneux Mathilde Hunault Pierre Peterlin Martin Carré Jacques-Olivier Bay Caroline Bonmati Maria-Pilar Gallego-Hernanz Bruno Lioure Philippe Bertrand Nicolas Vallet David Ternant François Darrouzain Frédéric Picou Marie-Christine Béné Christian Récher Olivier Hérault |
| author_sort | Emmanuel Gyan |
| collection | DOAJ |
| description | Abstract The treatment of acute myeloid leukemia (AML) with unfavorable cytogenetics treatment remains a challenge. We previously established that ex vivo exposure of AML blasts to eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), or fish oil emulsion (FO) induces Nrf2 pathway activation, metabolic switch, and cell death. The FILO group launched a pilot clinical study to evaluate the feasibility, safety, and efficacy of the adjunction of a commercial FO emulsion to 3 + 7 in untreated AML with unfavorable cytogenetics. The primary objective was complete response (CR). Thirty patients were included. FO administration raised the plasma levels of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids (p < 0.001). The pharmacokinetics of cytarabine and daunorubicin were unaffected. A historical comparison to the LAM2001 trial (Lioure et al. Blood 2012) found a higher frequency of grade 3 serious adverse events, with no drug-related unexpected toxicity. The CR rate was 77%, and the partial response (PR) 10%, not significantly superior to that of the previous study (CR 72%, PR 1%). RT-qPCR analysis of Nrf2 target genes and antioxidant enzymes did not show a significant in vivo response. Overall, FO emulsion adjunction to 3 + 7 is feasible. An improvement in CR was not shown in this cohort of high-risk patients. The present data does not support the use of FO in adjunction with 3 + 7 in high-risk AML patients. ClinicalTrials.gov identifier: NCT01999413. |
| first_indexed | 2024-12-12T12:16:43Z |
| format | Article |
| id | doaj.art-c5b28a8dd12a453e8e73b7f9e96cc55b |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-12T12:16:43Z |
| publishDate | 2022-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-c5b28a8dd12a453e8e73b7f9e96cc55b2022-12-22T00:24:45ZengNature PortfolioScientific Reports2045-23222022-06-011211910.1038/s41598-022-13626-yAdjunction of a fish oil emulsion to cytarabine and daunorubicin induction chemotherapy in high-risk AMLEmmanuel Gyan0Arnaud Pigneux1Mathilde Hunault2Pierre Peterlin3Martin Carré4Jacques-Olivier Bay5Caroline Bonmati6Maria-Pilar Gallego-Hernanz7Bruno Lioure8Philippe Bertrand9Nicolas Vallet10David Ternant11François Darrouzain12Frédéric Picou13Marie-Christine Béné14Christian Récher15Olivier Hérault16Service d’Hématologie et Thérapie Cellulaire, Centre Hospitalier Universitaire de Tours, Hôpital BretonneauClinique d’Hématologie, Université de Bordeaux, Hôpital Haut-LevêqueService des Maladies du Sang, FHU GOAL, CRCINA, INSERM Angers, Centre Hospitalier UniversitaireService d’Hématologie, Centre Hospitalier UniversitaireService d’Hématologie, Centre Hospitalier UniversitaireService d’Hématologie, Centre Hospitalier UniversitaireService d’Hématologie, Centre Hospitalier UniversitaireService d’Hématologie, Centre Hospitalier UniversitaireService d’Hématologie, Centre Hospitalier UniversitaireLaboratoire de Biostatistiques, Faculté de Médecine, Université de ToursService d’Hématologie et Thérapie Cellulaire, Centre Hospitalier Universitaire de Tours, Hôpital BretonneauLaboratoire de Pharmacologie-Toxicologie, Centre Hospitalier UniversitaireLaboratoire d’Hématologie, Centre Hospitalier UniversitaireERL CNRS 7001, Leukemic Niche and Redox Metabolism (LNOx), Faculté de Médecine, Université de ToursLaboratoire d’Hématologie, Centre Hospitalier UniversitaireService d’Hématologie, Institut Universitaire de Cancérologie de ToulouseERL CNRS 7001, Leukemic Niche and Redox Metabolism (LNOx), Faculté de Médecine, Université de ToursAbstract The treatment of acute myeloid leukemia (AML) with unfavorable cytogenetics treatment remains a challenge. We previously established that ex vivo exposure of AML blasts to eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), or fish oil emulsion (FO) induces Nrf2 pathway activation, metabolic switch, and cell death. The FILO group launched a pilot clinical study to evaluate the feasibility, safety, and efficacy of the adjunction of a commercial FO emulsion to 3 + 7 in untreated AML with unfavorable cytogenetics. The primary objective was complete response (CR). Thirty patients were included. FO administration raised the plasma levels of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids (p < 0.001). The pharmacokinetics of cytarabine and daunorubicin were unaffected. A historical comparison to the LAM2001 trial (Lioure et al. Blood 2012) found a higher frequency of grade 3 serious adverse events, with no drug-related unexpected toxicity. The CR rate was 77%, and the partial response (PR) 10%, not significantly superior to that of the previous study (CR 72%, PR 1%). RT-qPCR analysis of Nrf2 target genes and antioxidant enzymes did not show a significant in vivo response. Overall, FO emulsion adjunction to 3 + 7 is feasible. An improvement in CR was not shown in this cohort of high-risk patients. The present data does not support the use of FO in adjunction with 3 + 7 in high-risk AML patients. ClinicalTrials.gov identifier: NCT01999413.https://doi.org/10.1038/s41598-022-13626-y |
| spellingShingle | Emmanuel Gyan Arnaud Pigneux Mathilde Hunault Pierre Peterlin Martin Carré Jacques-Olivier Bay Caroline Bonmati Maria-Pilar Gallego-Hernanz Bruno Lioure Philippe Bertrand Nicolas Vallet David Ternant François Darrouzain Frédéric Picou Marie-Christine Béné Christian Récher Olivier Hérault Adjunction of a fish oil emulsion to cytarabine and daunorubicin induction chemotherapy in high-risk AML Scientific Reports |
| title | Adjunction of a fish oil emulsion to cytarabine and daunorubicin induction chemotherapy in high-risk AML |
| title_full | Adjunction of a fish oil emulsion to cytarabine and daunorubicin induction chemotherapy in high-risk AML |
| title_fullStr | Adjunction of a fish oil emulsion to cytarabine and daunorubicin induction chemotherapy in high-risk AML |
| title_full_unstemmed | Adjunction of a fish oil emulsion to cytarabine and daunorubicin induction chemotherapy in high-risk AML |
| title_short | Adjunction of a fish oil emulsion to cytarabine and daunorubicin induction chemotherapy in high-risk AML |
| title_sort | adjunction of a fish oil emulsion to cytarabine and daunorubicin induction chemotherapy in high risk aml |
| url | https://doi.org/10.1038/s41598-022-13626-y |
| work_keys_str_mv | AT emmanuelgyan adjunctionofafishoilemulsiontocytarabineanddaunorubicininductionchemotherapyinhighriskaml AT arnaudpigneux adjunctionofafishoilemulsiontocytarabineanddaunorubicininductionchemotherapyinhighriskaml AT mathildehunault adjunctionofafishoilemulsiontocytarabineanddaunorubicininductionchemotherapyinhighriskaml AT pierrepeterlin adjunctionofafishoilemulsiontocytarabineanddaunorubicininductionchemotherapyinhighriskaml AT martincarre adjunctionofafishoilemulsiontocytarabineanddaunorubicininductionchemotherapyinhighriskaml AT jacquesolivierbay adjunctionofafishoilemulsiontocytarabineanddaunorubicininductionchemotherapyinhighriskaml AT carolinebonmati adjunctionofafishoilemulsiontocytarabineanddaunorubicininductionchemotherapyinhighriskaml AT mariapilargallegohernanz adjunctionofafishoilemulsiontocytarabineanddaunorubicininductionchemotherapyinhighriskaml AT brunolioure adjunctionofafishoilemulsiontocytarabineanddaunorubicininductionchemotherapyinhighriskaml AT philippebertrand adjunctionofafishoilemulsiontocytarabineanddaunorubicininductionchemotherapyinhighriskaml AT nicolasvallet adjunctionofafishoilemulsiontocytarabineanddaunorubicininductionchemotherapyinhighriskaml AT davidternant adjunctionofafishoilemulsiontocytarabineanddaunorubicininductionchemotherapyinhighriskaml AT francoisdarrouzain adjunctionofafishoilemulsiontocytarabineanddaunorubicininductionchemotherapyinhighriskaml AT fredericpicou adjunctionofafishoilemulsiontocytarabineanddaunorubicininductionchemotherapyinhighriskaml AT mariechristinebene adjunctionofafishoilemulsiontocytarabineanddaunorubicininductionchemotherapyinhighriskaml AT christianrecher adjunctionofafishoilemulsiontocytarabineanddaunorubicininductionchemotherapyinhighriskaml AT olivierherault adjunctionofafishoilemulsiontocytarabineanddaunorubicininductionchemotherapyinhighriskaml |