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Background: Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common adverse events that can significantly impair the quality of life of patients. Although limb cooling may be beneficial for preventing CIPN, logistical challenges exist in ensuring consistent efficacy and safety. The purpose of this randomized controlled trial is to validate whether limb cooling with strict temperature control can reduce CIPN in patients with breast cancer receiving weekly paclitaxel as a perioperative treatment. Methods: This study is a multicenter, double-blinded, randomized controlled trial. We plan to enroll patients with breast cancer who are scheduled to receive 12 weekly doses of paclitaxel (60 min 80 mg/m2 intravenous infusion) as perioperative chemotherapy. Patients will be randomly divided into the intervention or control groups and undergo limb cooling therapy maintained at a constant temperature of 13°C and 25°C, respectively. The primary endpoint is the proportion of patients who report Patient Neurotoxicity Questionnaire (PNQ) ≥ D in their limbs by the end of the study treatment or at the time of discontinuation. Discussion: The results of this trial will contribute to the establishment of new evidence for limb cooling therapy in the mitigation of CIPN and present a safe and stable cooling device that may be suitable for use in the clinic. Clinical trial registration: https://jrct.niph.go.jp/en-latest-detail/jRCT2032210115, identifier jRCT2032210115.
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BACKGROUND/AIM: Aldehyde dehydrogenase (ALDH) 1A1 is a well-known marker for cancer stem cells (CSCs), characterized by self-renewal capacity and multidrug resistance in breast cancer. We developed a near-infrared turn-on fluorescence probe for ALDH1A1, C5S-A, which is suitable for observing and analyzing viable cells. Here, we demonstrated the utility of C5S-A in CSC research using breast cancer cell lines. MATERIALS AND METHODS: To evaluate concordance between C5S-A and conventional stem cell markers, breast cancer cells sorted for ALDEFLUOR-positive cells and for CD44+/CD24- cell populations were stained with C5S-A. Tumorigenicity of C5S-A-positive cells was examined by mammosphere formation assay and subcutaneous transplantation to immunodeficient mice. Additionally, to determine how long fluorescence from a single staining remained observable, we cultured breast cancer cells for 5 days after C5S-A staining. We then evaluated whether C5S-A-positive cells possessed resistance to cytotoxic drugs by chronological imaging. RESULTS: C5S-A staining showed good concordance with conventional breast CSC markers, and good utility for research into CSC characteristics in breast cancer cell lines, including tumorigenesis. Additionally, C5S-A was observable for more than 3 days with a single staining. Using this property, we then confirmed that C5S-A-positive cells possessed resistance to cytotoxic drugs, which is one of the characteristics of CSCs. CONCLUSION: We showed that C5S-A is suitable for CSC research using breast cancer cell lines, and confirmed its utility in observing cells over time.
Sujet(s)
Aldéhyde déshydrogénase-1/métabolisme , Marqueurs biologiques tumoraux/métabolisme , Tumeurs du sein/enzymologie , Colorants fluorescents , Cellules souches tumorales/enzymologie , Retinal dehydrogenase/métabolisme , Animaux , Antinéoplasiques/pharmacologie , Tumeurs du sein/traitement médicamenteux , Tumeurs du sein/anatomopathologie , Lignée cellulaire tumorale , Séparation cellulaire , Doxorubicine/pharmacologie , Résistance aux médicaments antinéoplasiques , Femelle , Cytométrie en flux , Humains , Souris de lignée NOD , Souris SCID , Microscopie de fluorescence , Cellules souches tumorales/effets des médicaments et des substances chimiques , Cellules souches tumorales/anatomopathologie , Paclitaxel/pharmacologie , Facteurs tempsRÉSUMÉ
We investigated the efficacy of BNT162b2 mRNA COVID-19 vaccine in patients with B-cell malignancies treated with anti-CD20 antibody. Although T-cell-mediated immune responses were detected even in patients receiving R-CHOP treatment, the S1 antibody titer following BNT162b2 vaccination remained only marginally increased for more than 3 years after the final dose of anti-CD20 antibody. We found no relationship between the percent of B-cells and S1 antibody titer. The duration of this suppression was much longer than we anticipated. Further protection and treatment strategies against COVID-19 for these patients are warranted.
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Anticorps monoclonaux humanisés/usage thérapeutique , Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique , Vaccin BNT162/usage thérapeutique , COVID-19/prévention et contrôle , Lymphome B/complications , Lymphome B/traitement médicamenteux , Sujet âgé , Sujet âgé de 80 ans ou plus , Production d'anticorps , Antigènes CD20/immunologie , COVID-19/immunologie , Cyclophosphamide/usage thérapeutique , Doxorubicine/usage thérapeutique , Femelle , Humains , Lymphome B/immunologie , Mâle , Adulte d'âge moyen , Prednisone/usage thérapeutique , Rituximab/usage thérapeutique , Vincristine/usage thérapeutiqueRÉSUMÉ
BACKGROUND: Although COVID-19 severity in cancer patients is high, the safety and immunogenicity of the BNT162b2 mRNA COVID-19 vaccine in patients undergoing chemotherapy for solid cancers in Japan have not been reported. METHODS: We investigated the safety and immunogenicity of BNT162b2 in 41 patients undergoing chemotherapy for solid cancers and in healthy volunteers who received 2 doses of BNT162b2. We evaluated serum IgG antibody titers for S1 protein by ELISA at pre-vaccination, prior to the second dose and 14 days after the second vaccination in 24 cancer patients undergoing cytotoxic chemotherapy (CC group), 17 cancer patients undergoing immune checkpoint inhibitor therapy (ICI group) and 12 age-matched healthy volunteers (HV group). Additionally, inflammatory cytokine levels were compared between the HV and ICI groups at pre and the next day of each vaccination. RESULTS: Anti-S1 antibody levels were significantly lower in the ICI and CC groups than in the HV group after the second dose (median optimal density: 0.241 [0.063-1.205] and 0.161 [0.07-0.857] vs 0.644 [0.259-1.498], p = 0.0024 and p < 0.0001, respectively). Adverse effect profile did not differ among the three groups, and no serious adverse event occurred. There were no differences in vaccine-induced inflammatory cytokines between the HV and ICI groups. CONCLUSION: Although there were no significant differences in adverse events in three groups, antibody titers were significantly lower in the ICI and CC groups than in the HV group. Further protection strategies should be considered in cancer patients undergoing CC or ICI.
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COVID-19 , Tumeurs , Anticorps antiviraux , Vaccin BNT162 , Vaccins contre la COVID-19/effets indésirables , Humains , Immunogénicité des vaccins , Tumeurs/traitement médicamenteux , Études prospectives , SARS-CoV-2RÉSUMÉ
BACKGROUND: Carboplatin is a key drug for ovarian cancer. However, it sometimes induces hypersensitivity reactions (HSRs) that result in the discontinuation of the treatment. Although various desensitization protocols have been reported in previous retrospective studies, a limited number of prospective studies have analyzed these protocols. METHODS: Patients with platinum-sensitive relapsed ovarian cancer who experienced carboplatin-induced HSRs were treated with diluted solutions of 1/1000, 1/100, 1/10 and an undiluted solution of carboplatin over a 1-h period. If no HSRs occurred within the first two cycles, a short protocol regimen over a 30-min period per solution was followed. The primary endpoint was treatment completion rate. RESULTS: Between May 2015 and September 2018, 21 patients were enrolled from two institutions. One patient experienced platinum-sensitive recurrence after the desensitization protocol; thus, 22 sessions were analyzed. Epinephrine use, treatment-related death, and intensive care unit (ICU) admissions did not occur. The median number of desensitization cycles was 6 (range 1-6). Two sessions were discontinued early because of grade 2 dysgeusia and grade 2 malaise. Treatment in two (9.1%) patients was discontinued because of HSR development. The treatment completion rate was 90.9%. Six (27.3%) sessions met the criteria for transition to the short protocol regimen. In 14 (63.6%) sessions, HSRs were observed during infusion of the undiluted solution. The median progression-free survival and overall survival were 14.8 and 23.8 months, respectively. CONCLUSION: This 4-step, 2-h carboplatin desensitization protocol is safe and feasible. Patients require careful monitoring with a rapid response to HSRs, especially during the administration of undiluted solutions.
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BACKGROUND: Trastuzumab emtansine (T-DM1) treatment for human epidermal growth factor receptor-2 (HER2)-positive metastatic breast cancer after taxane with trastuzumab and pertuzumab is standard therapy. However, treatment strategies beyond T-DM1 are still in development with insufficient evidence of their effectiveness. Here, we aimed to evaluate real-world treatment choice and efficacy of treatments after T-DM1 for HER2-positive metastatic breast cancer. METHODS: In this multi-centre retrospective cohort study involving 17 hospitals, 325 female HER2-positive metastatic breast cancer patients whose post-T-DM1 treatment began between April 15, 2014 and December 31, 2018 were enrolled. The primary end point was the objective response rate (ORR) of post-T-DM1 treatments. Secondary end points included disease control rate (DCR), progression-free survival (PFS), time to treatment failure (TTF), and overall survival (OS). RESULTS: The median number of prior treatments of post-T-DM1 treatment was four. The types of post-T-DM1 treatments included (1) chemotherapy in combination with trastuzumab and pertuzumab (n = 102; 31.4%), (2) chemotherapy concomitant with trastuzumab (n = 78; 24.0%), (3), lapatinib with capecitabine (n = 63; 19.4%), and (4) others (n = 82; 25.2%). ORR was 22.8% [95% confidence interval (CI): 18.1-28.0], DCR = 66.6% (95% CI 60.8-72.0), median PFS = 6.1 months (95% CI 5.3-6.7), median TTF = 5.1 months (95% CI 4.4-5.6), and median OS = 23.7 months (95% CI 20.7-27.4). CONCLUSION: The benefits of treatments after T-DM1 are limited. Further investigation of new treatment strategies beyond T-DM1 is awaited for HER2-positive metastatic breast cancer patients.
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Ado-trastuzumab emtansine/usage thérapeutique , Antinéoplasiques immunologiques/usage thérapeutique , Tumeurs du sein/traitement médicamenteux , Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Protocoles de polychimiothérapie antinéoplasique , Marqueurs biologiques tumoraux/analyse , Tumeurs du sein/mortalité , Tumeurs du sein/anatomopathologie , Femelle , Humains , Japon , Adulte d'âge moyen , Récepteur ErbB-2/analyse , Études rétrospectivesRÉSUMÉ
BACKGROUND/AIM: Dose-dense doxorubicin and cyclophosphamide (ddAC) followed by dose-dense paclitaxel (ddP) (ddAC-P) has improved disease-free survival of patients with breast cancer. The aim of this study was to evaluate the safety and relative dose intensity (RDI) of ddAC-P administered together with pegfilgrastim. PATIENTS AND METHODS: Between May 2015 and Aug 2017, 44 patients were retrospectively reviewed; they were administered 4 cycles of ddAC, followed by 4 cycles of ddP. Pegfilgrastim (3.6 mg) was administered in every cycle. RESULTS: The mean RDIs for ddAC-P, ddAC, and ddP were 95.0%, 94.5%, and 93.3%, respectively. The prevalence of high RDIs (≥85%) for ddAC-P, ddAC, and ddP was 90.9%, 84.1%, and 88.6%, respectively. Seven of the 10 patients with low RDIs experienced grade 1 or 2 fever. CONCLUSION: DdAC-P administered together with pegfilgrastim (3.6 mg) appears to be feasible and maintains RDI in most of Japanese patients with breast cancer. Rapid evaluation and proper management of fever may prevent low RDI.
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Tumeurs du sein/traitement médicamenteux , Cyclophosphamide/administration et posologie , Doxorubicine/administration et posologie , Paclitaxel/administration et posologie , Adulte , Sujet âgé , Tumeurs du sein/anatomopathologie , Cyclophosphamide/effets indésirables , Relation dose-effet des médicaments , Doxorubicine/effets indésirables , Femelle , Filgrastim/administration et posologie , Humains , Adulte d'âge moyen , Paclitaxel/effets indésirables , Polyéthylène glycols/administration et posologieRÉSUMÉ
After a brief summary of the current status of poly-ADP ribose polymerase (PARP) inhibitors for ovarian cancer, we summarize the current status of PARP inhibitors for BRCA wild type ovarian cancer, especially regarding gene alterations other than BRCA, homologous recombination deficiency (HRD), and combinations. Discussion of gene alterations other than BRCA include the results of multiple gene panels studying homologous recombination repair deficiency genes and cancer susceptibility genes, and influences of these alterations on efficacy of PARP inhibitors and cancer susceptibility. Discussions of HRD include the results of phase three trials using HRD assay, the definition of HRD assays, and the latest assays. Discussions of combinations include early phase trial results and ongoing trials combining PARP inhibitors with immune checkpoint inhibitors, anti-angiogenic agents, and triplets.
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Protéine BRCA1/génétique , Protéine BRCA2/génétique , Recombinaison homologue/génétique , Tumeurs de l'ovaire/traitement médicamenteux , Tumeurs de l'ovaire/génétique , Inhibiteurs de poly(ADP-ribose) polymérases/usage thérapeutique , Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique , Femelle , HumainsRÉSUMÉ
BACKGROUND: The development of skin rashes is the most common adverse event observed in cancer patients treated with epidermal growth factor receptor-tyrosine kinase inhibitors such as erlotinib. However, the pharmacological evidence has not been fully revealed. RESULTS: Erlotinib distribution in the rashes was more heterogeneous than that in the normal skin, and the rashes contained statistically higher concentrations of erlotinib than adjacent normal skin in the superficial skin layer (229 ± 192 vs. 120 ± 103 ions/mm2; P = 0.009 in paired t-test). LC-MS/MS confirmed that the concentration of erlotinib in the skin rashes was higher than that in normal skin in the superficial skin layer (1946 ± 1258 vs. 1174 ± 662 ng/cm3; P = 0.028 in paired t-test). The results of MALDI-MSI and LC-MS/MS were well correlated (coefficient of correlation 0.879, P < 0.0001). CONCLUSIONS: Focal distribution of erlotinib in the skin tissue was visualized using non-labeled MALDI-MSI. Erlotinib concentration in the superficial layer of the skin rashes was higher than that in the adjacent normal skin. METHODS: We examined patients with advanced pancreatic cancer who developed skin rashes after treatment with erlotinib and gemcitabine. We biopsied both the rash and adjacent normal skin tissues, and visualized and compared the distribution of erlotinib within the skin using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI). The tissue concentration of erlotinib was also measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) with laser microdissection.
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BACKGROUND: Inflammatory breast cancer (IBC) is the most aggressive form of primary breast cancer. CASE REPORT: A 40-year-old woman was referred to our hospital for evaluation of an induration in the right breast, suspected to be breast cancer. The tumor was diagnosed as estrogen receptor-negative, progesterone receptor-negative, HER2-positive, T4dN3cM0 stage IIIc IBC with axillary lymph node metastasis. Rather than surgical intervention, we chose a systemic treatment approach with pertuzumab, trastuzumab, and docetaxel (PTD) combination therapy which was shown to be effective for HER2-positive IBC in the NeoSphere trial. After 4 cycles of treatment, the patient had a partial response, allowing mastectomy of the right breast and axillary lymph node dissection to achieve local control. We review this case because of the success of PTD combination neoadjuvant chemotherapy for HER2-positive IBC. CONCLUSION: To improve the poor prognosis of IBC, combined modality therapy is required, including chemotherapy and local treatment such as surgery and/or radiation therapy. In this case, combination neoadjuvant chemotherapy with PTD for HER2-positive IBC was effective, and this regimen may contribute to further improvements in the cure rate for this malignancy.
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Moelle osseuse/métabolisme , Moelle osseuse/anatomopathologie , Hypercalcémie/complications , Mélanome/métabolisme , Mélanome/anatomopathologie , Molécules d'adhérence cellulaire neurales/métabolisme , Tumeurs cutanées/métabolisme , Tumeurs cutanées/anatomopathologie , Adulte , Issue fatale , Humains , Mâle ,RÉSUMÉ
PURPOSE: In a phase III study of gemcitabine plus erlotinib for advanced pancreatic cancer conducted in Canada, the incidence of interstitial lung disease (ILD) was 3.5 %. However, the incidence of ILD was reported as high as 8.5 % in a Japanese phase II study. These results suggest the influence of ethnic factors in the association of the use of gemcitabine plus erlotinib with the incidence of ILD. Here, we conducted a prospective study to analyze the relationship between human leukocyte antigen (HLA) alleles and ILD in Japanese patients with advanced pancreatic cancer receiving gemcitabine plus erlotinib. METHODS: Patients were treated with gemcitabine (1000 mg/m(2); administered by intravenous infusion on days 1, 8, and 15 every 4 weeks) and erlotinib (given orally at 100 mg/day). We compared the frequencies of HLA alleles in patients who did and did not develop ILD. RESULTS: A total of 57 patients were treated, and 4 patients (7.0 %) developed ILD. The combination of HLA-B*15:01 and DRB1*15:01 was observed in 2 of 4 patients (50 %) with ILD and in only 1 of 53 patients without ILD (2 %) resulting in odds ratio of 52.0 (95 % CI 3.2-842.5; p = 0.011). CONCLUSION: These results suggest that the combination of HLA-B*15:01 and DRB1*15:01 is associated with ILD in Japanese patients with advanced pancreatic cancer receiving gemcitabine plus erlotinib.
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Protocoles de polychimiothérapie antinéoplasique/effets indésirables , Désoxycytidine/analogues et dérivés , Chlorhydrate d'erlotinib/effets indésirables , Antigène HLA-B27/génétique , Chaines HLA-DRB1/génétique , Pneumopathies interstitielles/induit chimiquement , Tumeurs du pancréas/traitement médicamenteux , Administration par voie orale , Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Protocoles de polychimiothérapie antinéoplasique/administration et posologie , Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique , Désoxycytidine/administration et posologie , Désoxycytidine/effets indésirables , Désoxycytidine/usage thérapeutique , Calendrier d'administration des médicaments , Chlorhydrate d'erlotinib/administration et posologie , Chlorhydrate d'erlotinib/usage thérapeutique , Femelle , Fréquence d'allèle , Humains , Perfusions veineuses , Japon , Pneumopathies interstitielles/génétique , Mâle , Adulte d'âge moyen , Métastase tumorale , Tumeurs du pancréas/génétique , Tumeurs du pancréas/anatomopathologie , Études prospectives , Jeune adulte ,Sujet(s)
Infiltration leucémique/imagerie diagnostique , Foie/imagerie diagnostique , Leucémie-lymphome lymphoblastique à précurseurs B/diagnostic , Marqueurs biologiques tumoraux/métabolisme , Biopsie , Tumeurs du sein/complications , Tumeurs du sein/diagnostic , Tumeurs du sein/thérapie , Antigènes CD79/métabolisme , Diagnostic différentiel , Fatigue/étiologie , Femelle , Céphalée/étiologie , Humains , Infiltration leucémique/métabolisme , Infiltration leucémique/anatomopathologie , Infiltration leucémique/physiopathologie , Foie/métabolisme , Foie/anatomopathologie , Foie/physiopathologie , Tumeurs du foie/diagnostic , Tumeurs du foie/secondaire , Adulte d'âge moyen , Leucémie-lymphome lymphoblastique à précurseurs B/complications , Leucémie-lymphome lymphoblastique à précurseurs B/physiopathologie , Leucémie-lymphome lymphoblastique à précurseurs B/thérapie , Récidive , Tomodensitométrie , Urétérolithiase/complications , Urétérolithiase/imagerie diagnostique , Urétérolithiase/thérapieSujet(s)
Antinéoplasiques/effets indésirables , Asparaginase/effets indésirables , Lésions hépatiques dues aux substances/physiopathologie , Foie/effets des médicaments et des substances chimiques , Adulte , Antinéoplasiques/administration et posologie , Antinéoplasiques/usage thérapeutique , Protocoles de polychimiothérapie antinéoplasique/administration et posologie , Protocoles de polychimiothérapie antinéoplasique/effets indésirables , Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique , Asparaginase/administration et posologie , Asparaginase/usage thérapeutique , Lésions hépatiques dues aux substances/imagerie diagnostique , Lésions hépatiques dues aux substances/traitement médicamenteux , Cholagogues et cholérétiques/usage thérapeutique , Surveillance des médicaments , Femelle , Humains , Chimiothérapie d'induction/effets indésirables , Leucémie B/traitement médicamenteux , Foie/imagerie diagnostique , Agents protecteurs/usage thérapeutique , Radiographie , Indice de gravité de la maladie , Résultat thérapeutique , Acide ursodésoxycholique/usage thérapeutiqueRÉSUMÉ
Neuroendocrine carcinomas (NEC) of the female genital tract are aggressive and uncommon tumors, which usually involve the uterine cervix and ovary, and are seen very rarely in the endometrium. Only less than 10 cases of large cell NEC (LCNEC) of the endometrium have been reported in the literature and their radiological findings are not well described. We report here two cases of pathologically proven LCNEC of the uterine endometrium. In both cases, the uterine body was enlarged and the tumor occupied part of the uterine cavity. Endometrial mass exhibited heterogeneous high intensity on T2-weighted magnetic resonance (MR) images, and diffusion-weighted MR images revealed high intensity throughout the tumor, consistent with malignancy. LCNEC is a highly malignant neoplasm without particular findings in terms of diagnostic imaging and pathology, so its preoperative definitive diagnosis is very difficult. However, when laboratory test, pathologic diagnosis and MR imaging suggest a poorly differentiated uterine malignancy, positron emission tomography-computed tomography scan should be performed as a general assessment to help with diagnosis.