Survey of oxaliplatin-associated neurotoxicity using an interview-based questionnaire in patients with metastatic colorectal cancer

BACKGROUND: New chemotherapy regimens for patients with colorectal cancer have improved survival, but at the cost of clinical toxicity. Oxaliplatin, an agent used in first-line therapy for metastatic colorectal cancer, causes acute and chronic neurotoxicity. This study was performed to carefully assess the incidence, type and duration of oxaliplatin neurotoxicity. METHODS: A detailed questionnaire was completed after each chemotherapy cycle for patients with metastatic colorectal cancer enrolled in a phase I trial of oxaliplatin and capecitabine. An oxaliplatin specific neurotoxicity scale was used to grade toxicity. RESULTS: Eighty-six adult patients with colorectal cancer were evaluated. Acute neuropathy symptoms included voice changes, visual alterations, pharyngo-laryngeal dysesthesia (lack of awareness of breathing); peri-oral or oral numbness, pain and symptoms due to muscle contraction (spasm, cramps, tremors). When the worst neurotoxicity per patient was considered, grade 1/2/3/4 dysesthesias and paresthesias were seen in 71/12/5/0 and 66/20/7/1 percent of patients. By cycles 3, 6, 9, and 12, oxaliplatin dose reduction or discontinuation was needed in 2.7%, 20%, 37.5% and 62.5% of patients. CONCLUSION: Oxaliplatin-associated acute neuropathy causes a variety of distressing, but transient, symptoms due to peripheral sensory and motor nerve hyperexcitability. Chronic neuropathy may be debilitating and often necessitates dose reductions or discontinuation of oxaliplatin. Patients should be warned of the possible spectrum of symptoms and re-assured about the transient nature of acute neurotoxicity. Ongoing studies are addressing the treatment and prophylaxis of oxaliplatin neurotoxicity

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

Abstract: Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors

À la suite de la parution, dans le n° 1219, du Hors-dossier consacré à la nuit du 17 octobre 1961 et à sa mémoire, la rédaction de H&M a reçu le courrier suivant

Faivre Maurice. À la suite de la parution, dans le n° 1219, du Hors-dossier consacré à la nuit du 17 octobre 1961 et à sa mémoire, la rédaction de H&M a reçu le courrier suivant. In: Hommes et Migrations, n°1220, Juillet-août 1999. Islam d'en France. p. 132

Jean-Claude Jordi et Mohand Hamoumou Les harkis, une mémoire enfouie Autrement,"Français d'ailleurs peuple d'ici", 1999

Faivre Maurice. Jean-Claude Jordi et Mohand Hamoumou Les harkis, une mémoire enfouie Autrement,"Français d'ailleurs peuple d'ici", 1999. In: Hommes et Migrations, n°1219, Mai-juin 1999. Connaître et combattre les discriminations. p. 128

Jean-Claude Jordi et Mohand Hamoumou Les harkis, une mémoire enfouie Autrement,"Français d'ailleurs peuple d'ici", 1999

Faivre Maurice. Jean-Claude Jordi et Mohand Hamoumou Les harkis, une mémoire enfouie Autrement,"Français d'ailleurs peuple d'ici", 1999. In: Hommes et Migrations, n°1219, Mai-juin 1999. Connaître et combattre les discriminations. p. 128

Mohand Hamoumou ; Dominique Schnapper (préf.) : Et ils sont devenus harkis, 1993

Faivre Maurice. Mohand Hamoumou ; Dominique Schnapper (préf.) : Et ils sont devenus harkis, 1993. In: Hommes et Migrations, n°1167, juillet 1993. Mariages mixtes. pp. 60-61

K. D. Bouneb, Délit de faciès : Intégration des harkis ?, 1991

Faivre Maurice. K. D. Bouneb, Délit de faciès : Intégration des harkis ?, 1991. In: Hommes et Migrations, n°1151-1152, Février-mars 1992. Une autre Allemagne. Migrations et société multiculturelle en RFA. pp. 103-104

À propos de mémoire

Le général (CR) Maurice Faivre, lecteur assidu et à l'occasion collaborateur de H. & M., nous a envoyé un courrier ; dont on lira ci-dessous les principaux extraits, à propos de notre numéro 1175 d'avril 1994, «La mémoire retrouvée».Faivre Maurice. À propos de mémoire. In: Hommes et Migrations, n°1178, juillet 1994. Les lois «Pasqua». pp. 62-63

Les états généraux de la communauté des Français musulmans

Faivre Maurice. Les états généraux de la communauté des Français musulmans. In: Hommes et Migrations, n°1135, septembre 1990. Les Harkis et leurs enfants. p. 69

À la suite de la parution, dans le n° 1219, du Hors-dossier consacré à la nuit du 17 octobre 1961 et à sa mémoire, la rédaction de H&M a reçu le courrier suivant

Faivre Maurice. À la suite de la parution, dans le n° 1219, du Hors-dossier consacré à la nuit du 17 octobre 1961 et à sa mémoire, la rédaction de H&M a reçu le courrier suivant. In: Hommes et Migrations, n°1220, Juillet-août 1999. Islam d'en France. p. 132