0000000000476534
AUTHOR
Leila Bengrine-lefevre
Therapeutic drug monitoring as a tool to optimize 5-FU-based chemotherapy in gastrointestinal cancer patients older than 75 years.
Abstract Aims Most clinical trials exclude elderly people, leading to a limited understanding of the benefit-to-risk ratio in this population. Despite existing data regarding the oncological management of elderly receiving fluorouracil (5-FU)-based regimen, our objective was to investigate 5-FU exposure/toxicity relationship in patients ≥75 years and compare the effectiveness of 5-FU therapeutic drug monitoring between elderly and younger patients. Methods Hundred fifty-four patients (31 of whom are older than 75 years) with gastrointestinal cancers, who were to receive 5-FU–based regimens, were included in our study. At cycle 1 (C1), the 5-FU dose was calculated using patient's body surfac…
Accumulation of MDSC and Th17 Cells in Patients with Metastatic Colorectal Cancer Predicts the Efficacy of a FOLFOX-Bevacizumab Drug Treatment Regimen
Abstract Host immunity controls the development of colorectal cancer, and chemotherapy used to treat colorectal cancer is likely to recruit the host immune system at some level. Athough preclinical studies have argued that colorectal cancer drugs, such as 5-fluorouracil (5-FU) and oxaliplatin, exert such effects, their combination as employed in the oncology clinic has not been evaluated. Here, we report the results of prospective immunomonitoring of 25 metastatic colorectal cancer (mCRC) patients treated with a first-line combination regimen of 5-FU, oxaliplatin, and bevacizumab (FOLFOX–bevacizumab), as compared with 20 healthy volunteers. Before this therapy was initiated, T regulatory ce…
Treatment guidelines of metastatic colorectal cancer in older patients from the French Society of Geriatric Oncology (SoFOG)
International audience; Background: Several guidelines dedicated to metastatic colorectal cancer (mCRC) are available. Since 2013 no recent guidelines are specifically dedicated to older patients and based on a systematic review. Materials and methods: A multidisciplinary Task Force with digestive oncologists, geriatricians and methodologists from the SoFOG was formed in 2016 to update recommendations on medical treatment of mCRC based on a systematic review of publications from 2000 to 2018. Search strategy has followed a standardized protocol from the formulation of clinical questions and definition of a search algorithm to the selection of complete articles for recommendations. Results: …
Folfirinox in elderly patients with pancreatic or colorectal cancer-tolerance and efficacy
AIM To study the tolerance and the efficiency of FOLFIRINOX in elderly patients diagnosed with colorectal or pancreatic cancer. METHODS This retrospective study included elderly patients aged over 70 years of age treated at Georges-Francois Leclerc Center by FOLFIRINOX for histological proved colorectal or pancreatic cancer between January 2009 and January 2015. Chemotheapy regimen consisted of oxaliplatin (85 mg/m(2) in over 120 min) followed by leucovorin (400 mg/m(2) in over 120 min), with the addition, after 30 min of irinotecan (180 mg/m(2) in over 90 min) then 5 fluorouracil (5FU) (400 mg/m(2) administred intravenous bolus), followed by 5FU (2400 mg/m2 intraveinous infusion over 46 h)…
Efficacy of FOLFIRI-3 (irinotecan D1,D3 combined with LV5-FU) or other irinotecan-based regimens in oxaliplatin-pretreated metastatic colorectal cancer in the GERCOR OPTIMOX1 study
Abstract Background: Second-line irinotecan-based chemotherapy is commonly used in metastatic colorectal cancers after first-line oxaliplatin-based chemotherapy. No standard schedule of irinotecan has been established in this situation. Patients and methods: Metastatic colorectal cancer patients included in the OPTIMOX1 phase III study received first-line oxaliplatin-based chemotherapy (FOLFOX). No second line was defined in the protocol, but data concerning second line were prospectively registered. Inclusion criterion was patients receiving an irinotecan-based second-line chemotherapy. Second-line progression-free survival (PFS) and tumor response were evaluated according to type of irino…
Impact of granulocyte colony‐stimulating factor on FOLFIRINOX‐induced neutropenia prevention: A population pharmacokinetic/pharmacodynamic approach
Aims Granulocyte colony-stimulating factor (G-CSF) is frequently prescribed to prevent chemotherapy-induced neutropenia, but the administration schedule remains empirical in case of bimonthly chemotherapy such as FOLFIRINOX regimen. This pharmacokinetic/pharmacodynamic (PK/PD) study was performed to determine the effect of different G-CSF regimens on the incidence and duration of neutropenia following FOLFIRINOX administration in order to propose an optimal G-CSF dosing schedule. Methods A population PK/PD model was developed to describe individual neutrophil time course from absolute neutrophil counts (ANC) obtained in 40 advanced cancer patients receiving FOLFIRINOX regimen. The structura…
Association of 5-FU Therapeutic Drug Monitoring to DPD Phenotype Assessment May Reduce 5-FU Under-Exposure
In order to limit 5-fluorouracil (5-FU) toxicity, some health agencies recommend evaluating dihydropyrimidine dehydrogenase (DPD) deficiency before any 5-FU treatment introduction. In our study, we investigated relationships between 5-FU clearance and markers of DPD activity such as uracilemia (U), dihydrouracilemia (UH2)/U ratio, or genotype of the gene encoding DPD (DPYD). All patients with gastrointestinal cancers who received 5-FU-based regimens form March 2018 to June 2020 were included in our study. They routinely benefited of a pre-therapeutic DPYD genotyping and phenotyping. During 5-FU infusion, blood samples were collected to measure 5-FU steady-state concentration in order to ada…
Seroprevalence of SARs-CoV-2 among the staff and patients of a French cancer centre after first lockdown: the canSEROcov study
Abstract Background In view of the potential gravity of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection for patients with cancer, epidemiological data are vital to assess virus circulation among patients and staff of cancer centres. We performed a prospective study to investigate seroprevalence of SARS-CoV-2 antibodies among staff and patients with cancer at a large cancer centre, at the end of the period of first national lockdown in France and to determine factors associated with the risk of SARS-CoV-2 infection. Methods After the first lockdown, all medical and non-medical staff, as well as all patients attending the medical oncology department were invited to unde…
Expression of a mutant HSP110 sensitizes colorectal cancer cells to chemotherapy and improves disease prognosis
Heat shock proteins (HSPs) are necessary for cancer cell survival. We identified a mutant of HSP110 (HSP110ΔE9) in colorectal cancer showing microsatellite instability (MSI CRC), generated from an aberrantly spliced mRNA and lacking the HSP110 substrate-binding domain. This mutant was expressed at variable levels in almost all MSI CRC cell lines and primary tumors tested. HSP110ΔE9 impaired both the normal cellular localization of HSP110 and its interaction with other HSPs, thus abrogating the chaperone activity and antiapoptotic function of HSP110 in a dominant-negative manner. HSP110ΔE9 overexpression caused the sensitization of cells to anticancer agents such as oxaliplatin and 5-fluorou…
Management of elderly patients suffering from cancer: Assessment of perceived burden and of quality of life of primary caregivers
International audience; Objective: To evaluate the perceived burden and the quality of life (QoL) at 3 and 6 months of the primary caregiver (PC) of patients aged 70 and over suffering from cancer and the predictors of QoL in this population.Methods: In this prospective observational study, 98 patients aged 70 and older with cancer and 96 PCs were included between 01/06/2014 and 18/03/2015. The Medical Outcomes Study 12-item Short Form Health Survey (SF-12) was used to assess the QoL of PCs and the Zarit Burden Interview (ZBI) was used to measure the perceived burden at 3 and 6 months. The major determinants of QoL were identified using mixed linear models for the dimensions of the SF-12 th…