Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Hodgkin Disease/drug therapy , Hodgkin Disease/mortality , Salvage Therapy , Adult , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Brentuximab Vedotin/administration & dosage , Brentuximab Vedotin/adverse effects , Cisplatin/administration & dosage , Cisplatin/adverse effects , Cytarabine/administration & dosage , Cytarabine/adverse effects , Dexamethasone/administration & dosage , Dexamethasone/adverse effects , Disease-Free Survival , Female , Hodgkin Disease/pathology , Humans , Male , Middle Aged , Recurrence , Survival RateSubject(s)
Class I Phosphatidylinositol 3-Kinases/antagonists & inhibitors , Enzyme Inhibitors/administration & dosage , Hematologic Neoplasms/drug therapy , Lymphoproliferative Disorders/drug therapy , Adult , Aged , Aged, 80 and over , Enzyme Inhibitors/adverse effects , Female , Hematologic Neoplasms/enzymology , Humans , Lymphoproliferative Disorders/enzymology , Male , Middle Aged , RecurrenceABSTRACT
Resistance to chemotherapy-induced apoptosis in CLL is associated with overexpression of antiapoptotic proteins induced by signals from the microenvironment. In vitro, dasatinib effectively inhibits expression of anti-apoptotic regulators and restores fludarabine sensitivity in activated CLL. The aim of this study was to evaluate efficacy of one cycle of dasatinib monotherapy (100mg/day, days 1-28) followed by combination of dasatinib with fludarabine (40mg/m²/day, days 1-3 every 28 day) for a total of 6 cycles in fludarabine-refractory CLL. The primary endpoint was overall response rate according to the IWCLL'08 criteria. 20 patients were enrolled: 18 completed at least one cycle of treatment of which 67% finished at least 2 cycles of combination treatment. 3 of these 18 patients reached a formal PR (16.7%). Majority of patients obtained some reduction in lymph node (LN) size. Most frequent toxicity was related to myelosuppression. NF-κB RNA expression levels of circulating CLL cells decreased whereas the levels of pro-apoptotic NOXA increased during treatment. In conclusion, dasatinib/fludarabine combination has modest clinical efficacy in fludarabine-refractory patients.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Pyrimidines/therapeutic use , Thiazoles/therapeutic use , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/pharmacokinetics , Dasatinib , Drug Administration Schedule , Fatigue/chemically induced , Female , Gene Expression Regulation, Leukemic , Humans , Kaplan-Meier Estimate , Leukemia, Lymphocytic, Chronic, B-Cell/genetics , Leukemia, Lymphocytic, Chronic, B-Cell/metabolism , Lymph Nodes/drug effects , Lymph Nodes/pathology , Male , Middle Aged , NF-kappa B/genetics , Nausea/chemically induced , Pneumonia/chemically induced , Pyrimidines/administration & dosage , Pyrimidines/adverse effects , Thiazoles/administration & dosage , Thiazoles/adverse effects , Thrombocytopenia/chemically induced , Treatment Outcome , Vidarabine/administration & dosage , Vidarabine/adverse effects , Vidarabine/analogs & derivativesABSTRACT
BACKGROUND: This study aimed to evaluate the reliability and validity of two self-report physical activity (PA) questionnaires - the AQuAA (Activity Questionnaire for Adults and Adolescents) and PASE (Physical Activity Scale for the Elderly) - in cancer patients. METHODS: Test-retest reliability was determined by administering the questionnaires twice within 5 days. Intraclass correlation coefficient (ICC), standard error of measurement (SEM) and smallest detectable difference (SDD) were calculated. Construct validity was determined by comparing the questionnaire results with ActiGraph accelerometer scores using Spearman correlation coefficients (rs) and ICCs. Content validity was examined using the Three-Step Test-Interview (TSTI). RESULTS: Reliability for the AQuAA scores were fair to excellent (ICC = 0.57 to 0.78). Reliability for the PASE scores ranged from good to excellent (ICC = 0.67 to 0.90). Correlations between the ActiGraph and the AQuAA and the PASE were low (rs = 0.05 and 0.16 respectively, and ICC = -0.001 to 0.44). The TSTI showed that participants experienced difficulties with the examples provided with the questions, the perceptions of intensity level of PA, and with recalling the time spent on PA. CONCLUSIONS: Both questionnaires showed good to excellent test-retest reliability for most scores. Construct validity of both questionnaires was low, as indicated by the low correlations with the ActiGraph. Except for a few difficulties that participants perceived when filling out the questionnaires, the content validity of both questionnaires was good.
