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1.
Cancer Invest ; 37(3): 156-162, 2019.
Article in English | MEDLINE | ID: mdl-30907154

ABSTRACT

Mannose-binding lectin (MBL) - deficient patients who undergo chemotherapy for a solid tumor might have an increased risk developing febrile neutropenia (FN). We investigated in a prospective cohort study relations between MBL-serum levels and polymorphisms in MBL promotor genotypes (-550H/L and -221X/Y) on incidence and severity of FN. Risk of FN was 17.9% in MBL-deficient and 22.5% in MBL-sufficient patients (RR = 0.796, p = 0.45). Median MBL serum levels at baseline were respectively 1.39 µg/mL and 1.09 µg/mL (p = 0.92) in patients with and without FN. In conclusion, serum MBL and MBL genotypes (-550H/L and -221X/Y) do not determine the risk for developing FN.


Subject(s)
Chemotherapy-Induced Febrile Neutropenia/genetics , Mannose-Binding Lectin/genetics , Neoplasms/genetics , Polymorphism, Genetic , Promoter Regions, Genetic/genetics , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chemotherapy-Induced Febrile Neutropenia/blood , Female , Genotype , Humans , Male , Mannose-Binding Lectin/blood , Middle Aged , Neoplasms/blood , Neoplasms/drug therapy , Prognosis , Prospective Studies , Risk Factors
3.
Breast Cancer Res Treat ; 156(3): 557-566, 2016 Apr.
Article in English | MEDLINE | ID: mdl-27060914

ABSTRACT

Treatment with (neo)adjuvant chemotherapy for breast cancer, as currently given, causes cell damage by induction of double-strand DNA breaks. Because BRCA1 and BRCA2 proteins play a role in the repair of DNA damage, the efficacy of (neo)adjuvant chemotherapy may be increased in BRCA1/2-associated breast cancer patients. As a downside, acute chemotherapy-related toxicity may also be increased. We selected all female patients who were treated at the Erasmus MC Cancer Institute, with (neo)adjuvant chemotherapy for primary or locoregional recurrence of breast cancer (PBC/LR) between January 1, 2004 and December 31, 2014. The primary outcome was the relative total dose intensity (RTDI), calculated for anthracyclines and taxanes separately. Secondary outcomes were the occurrence of febrile neutropenia, delay in chemotherapy administration, and switch to another chemotherapy regimen due to toxicity. In total, 701 patients treated for PBC/LR were eligible for data analyses, among which 85 BRCA1/2 mutation carriers (n = 67 BRCA1 and n = 18 BRCA2). The mean RTDI for anthracyclines was not significantly different between both groups (98.7 % in the BRCA1/2, 96.6 % in the sporadic group, p = 0.27). Also the mean RTDI for taxanes was not significantly different between the groups (93.6 % in the BRCA1/2-associated, 90.0 % in the sporadic group, p = 0.12). Linear regression analysis revealed no significant effect of BRCA1/2 mutation carriership on the RTDIs. No significant differences were found in the percentages of patients presenting with febrile neutropenia, having a delay in chemotherapy administration or switching to an altered chemotherapy regimen. Additionally, the odds ratios showed no significant effect of BRCA1/2 mutation carriership on the secondary outcome variables. (Neo)adjuvant chemotherapy-related toxicity was not different between BRCA1/2-associated and sporadic breast cancer patients suggesting that the DNA damage repair mechanism of non-cancer cells with only one normal copy of either the BRCA1 or BRCA2 gene is sufficiently functional to handle acute chemotherapy-associated toxicity.


Subject(s)
BRCA1 Protein/genetics , BRCA2 Protein/genetics , Breast Neoplasms/drug therapy , Chemotherapy, Adjuvant/adverse effects , Germ-Line Mutation , Neoplasm Recurrence, Local/drug therapy , Adult , Aged , Anthracyclines/administration & dosage , Anthracyclines/adverse effects , Breast Neoplasms/genetics , Chemotherapy-Induced Febrile Neutropenia/epidemiology , Dose-Response Relationship, Drug , Female , Humans , Linear Models , Middle Aged , Neoplasm Recurrence, Local/genetics , Retrospective Studies , Taxoids/administration & dosage , Taxoids/adverse effects , Young Adult
5.
AIDS ; 24(10): 1387-405, 2010 Jun 19.
Article in English | MEDLINE | ID: mdl-20523204

ABSTRACT

OBJECTIVE: To assess predictors and reported treatment strategies of HIV-related fatigue in the combined antiretroviral (cART) era. METHOD: Five databases were searched and reference lists of pertinent articles were checked. Studies published since 1996 on predictors or therapy of HIV-related fatigue measured by a validated instrument were selected. RESULTS: A total of 42 studies met the inclusion criteria. The reported HIV-related fatigue prevalence in the selected studies varied from 33 to 88%. The strongest predictors for sociodemographic variables were unemployment and inadequate income. Concerning HIV-associated factors, the use of cART was the strongest predictor. Comorbidity and sleeping difficulties were important factors when assessing physiological influences. Laboratory parameters were not predictive of fatigue. The strongest and most uniform associations were observed between fatigue and psychological factors such as depression and anxiety. Reported therapeutic interventions for HIV-related fatigue include testosterone, psycho-stimulants (dextroamphetamine, methylphenidate hydrochloride, pemoline, modafinil), dehydroepiandrosterone, fluoxetine and cognitive behavioural or relaxation therapy. CONCLUSION: HIV-related fatigue has a high prevalence and is strongly associated with psychological factors such as depression and anxiety. A validated instrument should be used to measure intensity and consequences of fatigue in HIV-infected individuals. In the case of fatigue, clinicians should not only search for physical mechanisms, but should question depression and anxiety in detail. There is a need for intervention studies comparing the effect of medication (antidepressants, anxiolytics) and behavioural interventions (cognitive-behavioural therapy, relaxation therapy, graded exercise therapy) to direct the best treatment strategy. Treatment of HIV-related fatigue is important in the care for HIV-infected patients and requires a multidisciplinary approach.


Subject(s)
Anxiety/drug therapy , Fatigue/drug therapy , HIV Infections/complications , HIV-1 , Antiretroviral Therapy, Highly Active , Anxiety/complications , Anxiety/psychology , CD4 Lymphocyte Count , Fatigue/etiology , Fatigue/psychology , HIV Infections/drug therapy , HIV Infections/psychology , Humans , Risk Factors , Stress, Psychological , Viral Load
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