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1.
Breast Cancer Res Treat ; 153(3): 583-90, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26369533

ABSTRACT

Breast cancer patients with absent or reduced CYP2D6 activity and consequently low endoxifen levels may benefit less from tamoxifen treatment. CYP2D6 poor and intermediate metabolizers may need a personalized increased tamoxifen dose to achieve effective endoxifen serum concentrations, without increasing toxicity. From a prospective study population of early breast cancer patients using tamoxifen (CYPTAM: NTR1509), 12 CYP2D6 poor and 12 intermediate metabolizers were selected and included in a one-step tamoxifen dose escalation study during 2 months. The escalated dose was calculated by multiplying the individual's endoxifen level at baseline relative to the average endoxifen concentration observed in CYP2D6 extensive metabolizers by 20 mg (120 mg maximum). Endoxifen levels and tamoxifen toxicity were determined at baseline and after 2 months, just before patients returned to the standard dose of 20 mg. Tamoxifen dose escalation in CYP2D6 poor and intermediate metabolizers significantly increased endoxifen concentrations (p < 0.001; p = 0.002, respectively) without increasing side effects. In intermediate metabolizers, dose escalation increased endoxifen to levels comparable with those observed in extensive metabolizers. In poor metabolizers, the mean endoxifen level increased from 24 to 81 % of the mean concentration in extensive metabolizers. In all patients, the endoxifen threshold of 5.97 ng/ml (=16.0 nM) reported by Madlensky et al. was reached following dose escalation. CYP2D6 genotype- and endoxifen-guided tamoxifen dose escalation increased endoxifen concentrations without increasing short-term side effects. Whether such tamoxifen dose escalation is effective and safe in view of long-term toxic effects is uncertain and needs to be explored.


Subject(s)
Antineoplastic Agents, Hormonal/pharmacology , Antineoplastic Agents, Hormonal/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Cytochrome P-450 CYP2D6/genetics , Genotype , Tamoxifen/analogs & derivatives , Adult , Aged , Drug Monitoring , Female , Humans , Middle Aged , Pharmacogenetics , Phenotype , Prospective Studies , Risk Factors , Tamoxifen/pharmacology , Tamoxifen/therapeutic use , Treatment Outcome
2.
Ann Hematol ; 94(8): 1373-9, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25869027

ABSTRACT

Elderly patients with diffuse large B-cell lymphoma (DLBCL) are frequently not treated with standard immunochemotherapy, and this influences survival negatively. The purpose of this study was to gain more insight into treatment decision-making by hematologists. Case vignettes concerning patients with DLBCL were presented to hematologists in the Netherlands. Patient characteristics (age, comorbidity) differed per case. Respondents were asked in each case if they would treat the patient with curative intent by means of full-dose chemotherapy or chemotherapy with dose reduction or if they would not treat the patient with curative intent. The vast majority of respondents would treat an elderly patient diagnosed with DLBCL without a relevant medical history with full-dose chemotherapy irrespective of age. In the presence of comorbidity, lack of social support, cognitive disorders, and untreated depression dose reductions in advance are frequently applied or patients are not treated with curative intent. This is most pronounced for patients aged older than 80 years. Respondents working in a university hospital more frequently refrain form full-dose chemotherapy with curative intent compared to respondents working in tertiary medical teaching hospitals or general hospitals. Patients without a relevant medical history are generally treated with curative intent irrespective of age. Cognitive disorders, comorbidity, and depression reduce the change of being treated with curative intent. This is most prominent in the eldest patient category.


Subject(s)
Antineoplastic Agents/administration & dosage , Decision Making , Lymphoma, Large B-Cell, Diffuse/diagnosis , Lymphoma, Large B-Cell, Diffuse/drug therapy , Physician's Role , Age Factors , Aged , Aged, 80 and over , Female , Humans , Lymphoma, Large B-Cell, Diffuse/epidemiology , Male , Middle Aged , Surveys and Questionnaires , Treatment Outcome
3.
Neth J Med ; 72(3): 165-9, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24846934

ABSTRACT

BACKGROUND: Elderly patients with non-Hodgkin's lymphoma (NHL) are often not treated with standard immunochemotherapy and this might have a negative impact on their survival. Little is known about the determinants that play a role in treatment decision-making of clinicians regarding elderly patients with NHL. The objective of this study was to gain more insight into these determinants. METHODS: A survey was conducted amongst haematologists in the Netherlands. The survey contained questions about comorbidity, polypharmacy, social setting, nutritional status, depression, mild cognitive impairment, dementia, activities of daily living (ADL) and instrumental activities of daily living (IADL) in relation to treatment decisions in elderly NHL patients. RESULTS: Of all comorbidities, respondents designated cognitive disorders and cardiovascular comorbidity as the most important factors when assessing whether an older patient with NHL is eligible for curative treatment. Also in decreasing degree of importance ADL, IADL and depressive disorder are frequently included in treatment decision-making. Almost half of the respondents feel that treatment of the elderly person is complicated as a result of a lack of scientific evidence. CONCLUSION: Haematologists are aware of coexisting problems in elderly patients and they frequently take comorbidities, cognitive disorders and functional status into consideration in treatment decision-making. Future studies are needed to determine the exact role that these factors should play in the treatment of elderly patients. Furthermore, haematologists feel that treatment of the elderly is complicated and there is a lack of scientific evidence, and therefore older adults should be better represented in clinical trials.


Subject(s)
Antineoplastic Agents/administration & dosage , Hematology , Lymphoma, Non-Hodgkin/complications , Lymphoma, Non-Hodgkin/drug therapy , Practice Patterns, Physicians' , Activities of Daily Living , Aged , Cardiovascular Diseases/complications , Cognition Disorders/complications , Decision Making , Depression/complications , Female , Humans , Kidney Diseases/complications , Liver Diseases/complications , Lung Diseases/complications , Male , Middle Aged , Mobility Limitation , Netherlands , Nutritional Status , Polypharmacy
4.
Ann Oncol ; 25(5): 998-1004, 2014 May.
Article in English | MEDLINE | ID: mdl-24585721

ABSTRACT

BACKGROUND: The role of zoledronic acid (ZA) when added to the neoadjuvant treatment of breast cancer (BC) in enhancing the clinical and pathological response of tumors is unclear. The effect of ZA on the antitumor effect of neoadjuvant chemotherapy has not prospectively been studied before. PATIENTS AND METHODS: NEOZOTAC is a national, multicenter, randomized study comparing the efficacy of TAC (docetaxel, adriamycin and cyclophosphamide i.v.) followed by granulocyte colony-stimulating factor on day 2 with or without ZA 4 mg i.v. q 3 weeks inpatients withstage II/III, HER2-negative BC. We present data on the pathological complete response (pCR in breast and axilla), on clinical response using MRI, and toxicity. Post hoc subgroup analyses were undertaken to address the predictive value of menopausal status. RESULTS: Addition of ZA to chemotherapy did not improve pCR rates (13.2% for TAC+ZA versus 13.3% for TAC). Postmenopausal women (N = 96) had a numerical benefit from ZA treatment (pCR 14.0% for TAC+ZA versus 8.7% for TAC, P = 0.42). Clinical objective response did not differ between treatment arms (72.9% versus 73.7%). There was no difference in grade III/IV toxicity between treatment arms. CONCLUSIONS: Addition of ZA to neoadjuvant chemotherapy did not improve pathological or clinical response to chemotherapy. Further investigations are warranted in postmenopausal women with BC, since this subgroup might benefit from ZA treatment.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Receptor, ErbB-2/metabolism , Adult , Aged , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Chemotherapy, Adjuvant , Cyclophosphamide/administration & dosage , Diphosphonates/administration & dosage , Docetaxel , Doxorubicin/administration & dosage , Female , Humans , Imidazoles/administration & dosage , Middle Aged , Neoadjuvant Therapy , Neoplasm Staging , Prospective Studies , Taxoids/administration & dosage , Treatment Outcome , Zoledronic Acid
5.
Ann Oncol ; 25(3): 599-605, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24504445

ABSTRACT

BACKGROUND: Prospective data on chemotherapy for elderly patients with metastatic breast cancer (MBC) remain scarce. We compared the efficacy and safety of first-line chemotherapy with pegylated liposomal doxorubicin (PLD) versus capecitabine in MBC patients aged ≥65 years in a multicentre, phase III trial. PATIENTS AND METHODS: Patients were randomized to six cycles of PLD (45 mg/m(2) every 4 weeks) or eight cycles of capecitabine (1000 mg/m(2) twice daily, day 1-14 every 3 weeks). RESULTS: The study enrolled 78 of the planned 154 patients and was closed prematurely due to slow accrual and supply problems of PLD. Many included patients were aged ≥75 years (54%) and vulnerable (≥1 geriatric condition: 71%). The median dose intensity was 85% for PLD and 84% for capecitabine, respectively. In both arms, the majority of patients completed at least 12 weeks of treatment (PLD 73%; capecitabine 74%). After a median follow-up of 39 months, 77 patients had progressed and 62 patients had died of MBC. Median progression-free survival was 5.6 versus 7.7 months (P = 0.11) for PLD and capecitabine, respectively. Median overall survival was 13.8 months for PLD and 16.8 months for capecitabine (P = 0.59). Both treatments were feasible, grade 3 toxicities consisting of fatigue (both arms: 13%), hand-foot syndrome (PLD: 10%; capecitabine: 16%), stomatitis (PLD: 10%; capecitabine: 3%), exanthema (PLD: 5%) and diarrhoea (PLD: 3%; capecitabine: 5%). Only 1 of 10 patients aged ≥80 years completed chemotherapy, while 3 and 6 patients discontinued treatment due to toxicity or progressive disease, respectively. CONCLUSION: Both PLD and capecitabine demonstrated comparable efficacy and acceptable tolerance as first-line single-agent chemotherapy in elderly patients with MBC, even in vulnerable patients or patients aged ≥75 years. However, patients aged ≥80 years were unlikely to complete chemotherapy successfully. CLINICAL TRIAL NUMBERS: EudraCT 2006-002046-10; ISRCTN 11114726; CKTO 2006-09; BOOG 2006-02.


Subject(s)
Breast Neoplasms/drug therapy , Deoxycytidine/analogs & derivatives , Doxorubicin/analogs & derivatives , Fluorouracil/analogs & derivatives , Aged , Aged, 80 and over , Antibiotics, Antineoplastic/adverse effects , Antibiotics, Antineoplastic/pharmacology , Antimetabolites, Antineoplastic/adverse effects , Antimetabolites, Antineoplastic/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/mortality , Capecitabine , Deoxycytidine/adverse effects , Deoxycytidine/therapeutic use , Disease-Free Survival , Doxorubicin/adverse effects , Doxorubicin/therapeutic use , Female , Fluorouracil/adverse effects , Fluorouracil/therapeutic use , Humans , Neoplasm Metastasis/drug therapy , Netherlands , Polyethylene Glycols/adverse effects , Polyethylene Glycols/therapeutic use , Prospective Studies , Treatment Outcome
6.
Breast ; 23(1): 81-7, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24314824

ABSTRACT

AIM: To evaluate the association between baseline comprehensive geriatric assessment (CGA) or the Groningen Frailty Indicator (GFI) and toxicity in elderly metastatic breast cancer (MBC) patients treated with first-line palliative chemotherapy. PATIENTS AND METHODS: MBC patients (≥65 years) were randomized between pegylated liposomal doxorubicine or capecitabine. CGA included instrumental activities of daily living (IADL), cognition using the mini-mental state examination (MMSE), mood using the geriatric depression scale (GDS), comorbidity using the Charlson index, polypharmacy and nutritional status using the body mass index. Frailty on CGA was defined as one or more of the following: IADL ≤ 13, MMSE ≤ 23, GDS ≥ 5, BMI ≤ 20, ≥5 medications or Charlson ≥2. The cut-off for frailty on the GFI was ≥4. RESULTS: Of the randomized 78 patients (median age 75.5 years, range 65.8-86.8 years), 73 were evaluable for CGA; 52 (71%) had one or more geriatric conditions. Grade 3-4 chemotherapy-related toxicity was experienced by 19% of patients without geriatric conditions compared to 56% of patients with two geriatric conditions and 80% of those with three or more (p = 0.002). Polypharmacy was the only individual factor significantly associated with toxicity (p = 0.001). GFI had a sensitivity of 69% and a specificity of 76% for frailty on CGA, and was not significantly associated with survival or toxicity. CONCLUSION: In this study of elderly patients with MBC, the number of geriatric conditions correlated with grade 3-4 chemotherapy-related toxicity. Therefore, in elderly patients for whom chemotherapy is being considered, a CGA could be a useful addition to the decision-making process.


Subject(s)
Antineoplastic Agents/adverse effects , Breast Neoplasms/drug therapy , Deoxycytidine/analogs & derivatives , Doxorubicin/analogs & derivatives , Fluorouracil/analogs & derivatives , Geriatric Assessment , Activities of Daily Living , Aged , Aged, 80 and over , Antineoplastic Agents/therapeutic use , Body Mass Index , Breast Neoplasms/epidemiology , Breast Neoplasms/pathology , Capecitabine , Cognition Disorders/epidemiology , Comorbidity , Deoxycytidine/adverse effects , Deoxycytidine/therapeutic use , Depression/epidemiology , Doxorubicin/adverse effects , Doxorubicin/therapeutic use , Fatigue/chemically induced , Female , Fluorouracil/adverse effects , Fluorouracil/therapeutic use , Frail Elderly , Hand-Foot Syndrome/etiology , Humans , Mental Status Schedule , Palliative Care , Polyethylene Glycols/adverse effects , Polyethylene Glycols/therapeutic use , Polypharmacy , Risk Factors , Stomatitis/chemically induced , Treatment Outcome
7.
Breast ; 22(5): 753-60, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23414850

ABSTRACT

INTRODUCTION: The prognostic value of geriatric assessment in older patients with breast cancer treated with chemotherapy is largely unknown. METHODS: Fifty-five patients with advanced breast cancer aged 70 years or older were assessed by Mini Nutritional Assessment (MNA), Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), Groningen Frailty Indicator (GFI) and Mini Mental State Examination (MMSE). Levels of albumin, hemoglobin, creatinine and lactate dehydrogenase were measured. Patients completing at least four cycles of chemotherapy were reassessed by GFI and MMSE and mortality was evaluated using Cox regression analysis. RESULTS: The mean age was 76 year (SD 4.8). Inferior MNA and GFI scores were associated with increased hazard ratios for mortality: 3.05 (95% confidence interval [CI]: 1.44-6.45; p = 0.004) and 3.40 (95% CI: 1.62-7.10; p = 0.001), respectively. Physical aspects of frailty worsened during the course of chemotherapy. Laboratory values were not associated with assessment scores nor were they predictive for mortality. CONCLUSIONS: Malnutrition and frailty, rather than cognitive impairment and laboratory values, were associated with an increased mortality risk in these elderly breast cancer patients with advanced breast cancer.


Subject(s)
Breast Neoplasms/drug therapy , Geriatric Assessment , Aged , Aged, 80 and over , Antineoplastic Agents/therapeutic use , Breast Neoplasms/blood , Breast Neoplasms/complications , Breast Neoplasms, Male/blood , Breast Neoplasms, Male/drug therapy , Breast Neoplasms, Male/mortality , Cognition Disorders/complications , Creatinine/blood , Female , Hemoglobins/metabolism , Humans , Kaplan-Meier Estimate , L-Lactate Dehydrogenase/blood , Male , Malnutrition/complications , Prognosis , Proportional Hazards Models , Serum Albumin/metabolism
8.
Breast ; 22(4): 556-9, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23305962

ABSTRACT

BACKGROUND: In a Dutch multicentre study, elderly (65 + year) metastatic breast cancer patients, eligible for first-line chemotherapy, were randomised between two types of single-agent chemotherapy. As accrual was slow, with 78 randomised patients between April 2007 and September 2011, we explored potential barriers in the accrual process and their consequences for characteristics of included patients. METHODS: We sent surveys on the reasons for non-inclusion to all coordinating investigators. We also examined inclusion in a concurrent, non-elderly breast cancer study of the trialists' group and analysed baseline geriatric characteristics of included patients. RESULTS: Investigators from fifteen participating centres returned the survey. Most commonly reported barriers to inclusion were: patient's refusal of chemotherapy (n = 8) or of randomisation (n = 9), impaired cognition (n = 3) and insufficient cardiac function (n = 2). Oncologists' preference for combination regimens over single-agent chemotherapy was reported twice. Twenty-eight potentially eligible patients, aged 65-71 years, were included in a concurrent, study investigating combination chemotherapy in fit non-elderly patients with metastatic breast cancer. However, baseline characteristics of the included patients showed that the OMEGA study succeeded in including frail and older patients, with a performance status of 2 in 22% of patients and 54% of patients aged 75 years or older. CONCLUSION: Accrual in this study was mainly hampered by patient's refusal or preference for a particular type of treatment, and an overall condition considered as too fit or too frail for inclusion. Future trials in elderly metastatic breast cancer patients should focus on non-restrictive inclusion criteria as well as on education of physicians and elderly patients on the advantages of trial participation.


Subject(s)
Antineoplastic Agents/therapeutic use , Breast Neoplasms/drug therapy , Patient Selection , Randomized Controlled Trials as Topic/methods , Aged , Aged, 80 and over , Breast Neoplasms/pathology , Female , Humans , Netherlands , Treatment Refusal
9.
Eur J Surg Oncol ; 38(2): 110-7, 2012 Feb.
Article in English | MEDLINE | ID: mdl-22172646

ABSTRACT

AIMS: The aim of this study was to investigate non-compliance to aromatase inhibitors and factors associated with early treatment discontinuation in the extended adjuvant setting. METHODS: The IDEAL trial is a prospective, open-label phase-III trial comparing 2.5 with 5 years of extended adjuvant letrozole (LET) in hormone receptor positive (HR+) postmenopausal early breast-cancer patients after 5 years of adjuvant endocrine therapy (ET). The purpose of this study was to assess non-compliance in the first 2.5 years of extended adjuvant therapy. Non-compliance was defined as early discontinuation of LET for all reasons, excluding death or recurrence. RESULTS: At 2.5 years, 1215 patients were included in the analysis. Overall non-compliance probability was 18.4%, of which 85.1% discontinued due to toxicities. Analyses showed that patients with prior sequential therapy were less likely to discontinue treatment than when treated with AI or TAM upfront (logrank p = 0.004). Longer treatment-free intervals also predicted more non-compliance (logrank p = 0.011). Age was not predictive of non-compliance (p = 0.571). Prior surgery (mastectomy vs breast conserving surgery), both with or without radiotherapy and/or chemotherapy were also not associated with early treatment discontinuation (p = 0.228 and p = 0.585 respectively). Although having fewer than four positive lymph nodes predicted more non-compliance (logrank p = 0.050), age, tumor type and locoregional treatment did not. CONCLUSIONS: High non-compliance to extended ET was confirmed. Toxicities were the major reason for discontinuation, and this was not influenced by age. Longer treatment-free intervals and fewer positive lymph nodes predicted more non-compliance. Patients who underwent sequential therapy were least likely to discontinue extended adjuvant ET.


Subject(s)
Antineoplastic Agents, Hormonal/administration & dosage , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Nitriles/therapeutic use , Patient Compliance/statistics & numerical data , Triazoles/therapeutic use , Adult , Aged , Antineoplastic Agents, Hormonal/adverse effects , Breast Neoplasms/mortality , Breast Neoplasms/surgery , Chemotherapy, Adjuvant , Confidence Intervals , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Letrozole , Long-Term Care , Mastectomy, Segmental , Maximum Tolerated Dose , Middle Aged , Neoplasm Staging , Nitriles/adverse effects , Prospective Studies , Risk Assessment , Statistics, Nonparametric , Survival Rate , Time Factors , Treatment Outcome , Triazoles/adverse effects
10.
Crit Rev Oncol Hematol ; 79(2): 205-12, 2011 Aug.
Article in English | MEDLINE | ID: mdl-20709565

ABSTRACT

INTRODUCTION: Comprehensive geriatric assessment (CGA) gives useful information on the functional status of older cancer patients. However, its meaning for a proper selection of elderly patients before chemotherapy and, even more important, the influence of chemotherapy on the outcome of geriatric assessment is unknown. METHODS: 202 cancer patients, for whom an indication for chemotherapy was made by the medical oncologist, underwent a GA before start of chemotherapy by Mini Nutritional Assessment (MNA), Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), Groningen Frailty Index (GFI) and Mini Mental State Examination (MMSE). After completion of a minimum of four cycles of chemotherapy or at 6 months after the start of chemotherapy the GFI and MMSE assessment was repeated. RESULTS: Frailty was shown in 10% of patients by means of MMSE, 32% by MNA, 37% by GFI and in 15% by IQCODE. Compared to patients who received 4 or more cycles of chemotherapy, the MNA and MMSE scores were significantly lower for patients treated with less than 4 cycles (p = 0.001 and p = 0.04 respectively). The mortality rate after start of chemotherapy was increased for patients with low MNA and high GFI scores with hazard ratios of 2.19 (95% confidence interval [CI]: 1.42-3.39; p < 0.001) and 1.80 (95% CI: 1.17-2.78; p = 0.007), respectively. After adjusting for sex, age, purpose of chemotherapy and type of malignancy these hazard ratios remained significant (p < 0.001 and p = 0.004), respectively. Finally, for the 51 patients who underwent repeated post-chemotherapy evaluation by GFI and MMSE, a statistically significant deterioration for the MMSE (p = 0.041) was found but not for the GFI. CONCLUSIONS: Both inferior MNA and MMSE scores increased the probability not to complete chemotherapy. Also, an inferior score for MNA and GFI showed an increased mortality risk after the start of chemotherapy. The mean MMSE score worsened significantly during chemotherapy.


Subject(s)
Antineoplastic Agents/therapeutic use , Geriatric Assessment , Neoplasms/drug therapy , Activities of Daily Living/psychology , Aged , Aged, 80 and over , Antineoplastic Agents/administration & dosage , Cognition/physiology , Female , Frail Elderly , Geriatric Assessment/methods , Humans , Male , Neoplasms/mortality , Neoplasms/pathology , Nutrition Assessment , Predictive Value of Tests , Research Design , Risk Factors , Surveys and Questionnaires , Survival Analysis
11.
Ann Oncol ; 21(5): 974-82, 2010 May.
Article in English | MEDLINE | ID: mdl-19875752

ABSTRACT

BACKGROUND: The Tamoxifen and Exemestane Adjuvant Multinational (TEAM) trial investigates the efficacy and safety of adjuvant exemestane alone and in sequence after tamoxifen in postmenopausal women with hormone-sensitive early breast cancer. As there was a nationwide participation in The Netherlands, we studied the variations in patterns of care in the Comprehensive Cancer Centre Regions (CCCRs) and compliance with national guidelines. METHODS: Clinicopathological characteristics, carried out local treatment strategies and adjuvant chemotherapy data were collected. RESULTS: From 2001 to January 2006, 2754 Dutch patients were randomised to the study. Mean age of patients was 65 years (standard deviation 9). Tumours were < or =2 cm in 46% (within CCCRs 39%-50%), node-negative disease varied from 25% to 45%, and PgR status was determined in 75%-100% of patients. Mastectomy was carried out in 55% (45%-70%), sentinel lymph node procedure in 68% (42%-79%) and axillary lymph node dissections in 77% (67%-83%) of patients, all different between CCCRs (P < 0.0001). Adjuvant chemotherapy was given in 15%-70% of eligible patients (P < 0.001). DISCUSSION: In spite of national guidelines, breast cancer treatment on specific issues widely varied between the various Dutch regions. These data provide valuable information for breast cancer organisations indicating (lack of) guideline adherence and areas for breast cancer care improvement.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Neoplasms, Hormone-Dependent/drug therapy , Postmenopause , Practice Patterns, Physicians' , Aged , Androstadienes/administration & dosage , Breast Neoplasms/pathology , Breast Neoplasms/surgery , Chemotherapy, Adjuvant , Combined Modality Therapy , Female , Humans , International Agencies , Middle Aged , Neoplasms, Hormone-Dependent/pathology , Neoplasms, Hormone-Dependent/surgery , Practice Guidelines as Topic , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , Retrospective Studies , Survival Rate , Tamoxifen/administration & dosage , Treatment Outcome
12.
Neth J Med ; 67(10): 353-5, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19915230

ABSTRACT

A 35-year-old man presented at the outpatient department of pulmonary diseases with fever, rhinitis and coughing. He had recently been on holiday in California. Except for a body temperature of 39.7 degrees C there were no other abnormal findings at the physical examination. Chest X-ray showed a consolidation in the left upper lobe. Under antibiotic treatment his clinical condition deteriorated. Coccidioidomycosis was the suspected diagnosis and confirmed by the results of CT scanning and culture of bronchoalveolar lavage fluid. Treatment with itraconazole resulted in lasting improvement. The case stipulates the importance of travel history.


Subject(s)
Coccidioidomycosis/diagnosis , Lung Diseases, Fungal/diagnosis , Travel , Adult , Antifungal Agents/therapeutic use , Bronchoalveolar Lavage Fluid , California , Coccidioidomycosis/drug therapy , Coccidioidomycosis/etiology , Desert Climate , Humans , Itraconazole/therapeutic use , Lung Diseases, Fungal/drug therapy , Lung Diseases, Fungal/etiology , Male , Netherlands , Tomography, X-Ray Computed , Treatment Failure
13.
Neth J Med ; 67(8): 355-8, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19767667

ABSTRACT

BACKGROUND: To determine whether the reported increase in survival of patients with diffuse large B-cell malignant lymphoma (DLBCL) after the introduction of rituximab is also seen in a non-academic hospital in the Netherlands. A retrospective study. METHODS: A dataset was made containing all newly diagnosed patients with DLBCL in a period of 2.5 years before until 2.5 years after introduction of rituximab in the standard treatment. Total follow-up time was 6.5 years with a minimal follow-up of 18 months. RESULTS: The study population consisted of 65 patients; 32 in the prerituximab group (median follow-up time 60 months) and 33 in the postrituximab group (median follow-up time 29 months). Progression-free survival increased significantly in the postrituximab group (hazard ratio 0.31; 95% CI 0.12 to 0.78; p=0.013; log rank p=0.008). The overall survival also showed a significant increase (p=0.048). The 18-month progression-free survival increased from 59.4 to 81.8%; the overall survival at 18 months showed an increase from 65.5 to 81.8%. CONCLUSION: The introduction of rituximab in the treatment of DLB CL with CHOP chemotherapy has resulted in a significantly better prognosis for patients with DLBCL, treated in the Reinier de Graaf Gasthuis in Delft.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Antineoplastic Agents/therapeutic use , Lymphoma, Large B-Cell, Diffuse/drug therapy , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal, Murine-Derived , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Confidence Intervals , Cyclophosphamide/administration & dosage , Databases, Factual , Disease Progression , Doxorubicin/administration & dosage , Female , Heart Rate , Humans , Kaplan-Meier Estimate , Lymphoma, Large B-Cell, Diffuse/mortality , Lymphoma, Large B-Cell, Diffuse/radiotherapy , Male , Middle Aged , Prednisone/administration & dosage , Prognosis , Radiotherapy, Adjuvant , Retrospective Studies , Rituximab , Time Factors , Vincristine/administration & dosage
14.
Ned Tijdschr Geneeskd ; 152(11): 606-14, 2008 Mar 15.
Article in Dutch | MEDLINE | ID: mdl-18410020

ABSTRACT

An 82-year-old man was admitted with a 1-week history of chilling fever and dry cough. Laboratory tests revealed pancytopenia and elevated levels of C-reactive protein and lactic dehydrogenase (LDH). Screening for infectious diseases was negative. A bone marrow biopsy showed aspecific findings. The combination of pancytopenia, persistent fever, elevated LDH and hepatomegaly (demonstrated by ultrasound examination of the abdomen) was suggestive of the haemophagocytic syndrome. This was confirmed by very high levels of ferritin and soluble interleukin-2 receptor in the blood. In addition, re-examination of the bone marrow showed several haemophagocytic histiocytes. A polymerase chain reaction for Epstein-Barr virus (EBV) revealed a very high viral load. Since the patient had a history of an increased level of anti-EBV immunoglobulin-G, this was explained by a reactivation of the EBV infection. On the sixth day in hospital the patient developed signs of bilateral pneumonia and subsequent multiple organ failure. Despite intensive treatment the patient died. Autopsy revealed no haematological or other malignancies, but did show haemophagocytosis in many organs. It was then concluded that the patient had a virus-associated haemophagocytic syndrome, due to a reactivation of EBV, for which no underlying cause was found.


Subject(s)
Epstein-Barr Virus Infections/diagnosis , Herpesvirus 4, Human/isolation & purification , Lymphohistiocytosis, Hemophagocytic/diagnosis , Aged, 80 and over , C-Reactive Protein/analysis , Epstein-Barr Virus Infections/blood , Epstein-Barr Virus Infections/complications , Fatal Outcome , Fever of Unknown Origin/etiology , Humans , Lymphohistiocytosis, Hemophagocytic/blood , Lymphohistiocytosis, Hemophagocytic/complications , Male , Pancytopenia/etiology
15.
Neth J Med ; 65(11): 448-51, 2007 Dec.
Article in English | MEDLINE | ID: mdl-18079568

ABSTRACT

Analysis of an 83-year-old male presenting with diarrhoea showed secretory diarrhoea. serum levels of gastrin and pancreatic polypeptide were elevated. Somatostatin-receptor scintigraphy revealed a hot spot in the left thoracic wall and subsequently, breast adenocarcinoma with neuroendocrine differentiation was diagnosed. Postoperatively, the patient made an uneventful recovery. The relationship between the clinical picture, the results of pathological examination and hormonal analysis is discussed and put into perspective.


Subject(s)
Breast Neoplasms/pathology , Diarrhea/etiology , Aged, 80 and over , Breast Neoplasms/complications , Gastrins , Humans , Male , Neuroendocrine Tumors/complications , Neuroendocrine Tumors/pathology , Pancreatic Polypeptide
16.
Neth J Med ; 62(6): 198-200, 2004 Jun.
Article in English | MEDLINE | ID: mdl-15460500

ABSTRACT

We describe a 68-year-old woman with an episode of diarrhoea, malaise and weight loss, caused by infection with Cryptosporidium. The diagnosis was hampered because this patient had a low risk of HIV infection, a two-year history of Crohn's disease, and a simultaneous candidal infection. An infection with Cryptosporidium was demonstrated with electron microscopic examination, and subsequent tests revealed positive HIV serology. AIDS was probably contracted through her husband.


Subject(s)
AIDS-Related Opportunistic Infections/diagnosis , Cryptosporidiosis/diagnosis , Aged , Female , Humans , Incidental Findings
17.
Leuk Lymphoma ; 45(1): 101-7, 2004 Jan.
Article in English | MEDLINE | ID: mdl-15061204

ABSTRACT

The prognostic significance of age was studied in 372 patients with diffuse large B-cell non-Hodgkin's lymphoma, in relation to the prognostic factors of overexpressed BCL2 and p53 oncoprotein. Overexpression of BCL2 and p53 oncoprotein was defined when more than 50% of the tumor cells showed positive staining. The data were analyzed with respect to the age groups < 65 and > or = 65 years of age. There was a trend for BCL2 overexpression to occur significantly more often among patients older than 65 years of age (P = 0.065). Patients with BCL2 overexpression showed significantly inferior disease free survival rate, but only for patients younger than 65 years (log-rank test P = 0.0002), and the overexpression showed also an independent prognostic significance (P < 0.001). With respect to overexpressed p53 a significant difference was reached for complete remission rate (P = 0.01) and 5-year survival rate (log-rank test P = 0.04), again only for the younger age group. When the analyses were repeated for the older patients who had been treated adequately, the same lack of significance was found, both for BCL2 and p53. This study demonstrates that the negative prognostic value of overexpressed BCL2 and p53 protein is not of concern for patients older than 65 years of age. Among elderly patients the International Prognostic Index score seems the predominant risk factor for inferior prognosis.


Subject(s)
Aged , Lymphoma, Large B-Cell, Diffuse/diagnosis , Lymphoma, Large B-Cell, Diffuse/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism , Registries , Tumor Suppressor Protein p53/metabolism , Disease-Free Survival , Humans , Immunohistochemistry , Lymphoma, Large B-Cell, Diffuse/pathology , Middle Aged , Prognosis , Survival Rate
18.
Ned Tijdschr Geneeskd ; 147(43): 2089-94, 2003 Oct 25.
Article in Dutch | MEDLINE | ID: mdl-14619195

ABSTRACT

Three patients, a girl aged 10 and two women aged 59 and 64 years, had erythema multiforme, Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), respectively. SJS and TEN are rare illnesses with a high morbidity and mortality. The aetiology is mainly iatrogenic: a hypersensitivity reaction to certain pharmaceutical prescriptions. SJS and TEN should be differentiated from the more frequent erythema multiforme, a self-limiting disease without important residual symptoms, which is usually initiated by infection with herpes simplex virus. SJS and TEN are variants in a spectrum of exfoliative dermatoses with epidermal necrosis. SJS and TEN on the one hand and erythema multiforme on the other can be distinguished on the basis of aetiology, clinical symptoms and histopathology. The distinction can, however, be difficult, notably in the early stages. The girl recovered completely. The first woman was treated with corticosteroids and also recovered; she was thought to have developed the syndrome as a reaction to malarial prophylactics. The third patient died, despite extensive treatment, of multiorgan failure and sloughing of 70% of the skin, probably as a reaction to amoxicillin given for pneumococcal pneumonia.


Subject(s)
Erythema Multiforme/diagnosis , Stevens-Johnson Syndrome/diagnosis , Child , Diagnosis, Differential , Erythema Multiforme/pathology , Erythema Multiforme/therapy , Fatal Outcome , Female , Humans , Iatrogenic Disease , Middle Aged , Prognosis , Stevens-Johnson Syndrome/pathology , Stevens-Johnson Syndrome/therapy
19.
Ann Hematol ; 82(11): 661-70, 2003 Nov.
Article in English | MEDLINE | ID: mdl-12923662

ABSTRACT

With rising age the incidence of non-Hodgkin's lymphoma (NHL), together with the fact that the proportion of people older than 65 years in Western populations will double during the next 40 years, poses the challenge to adequately meet the needs of elderly patients. After a general introduction on cancer in the elderly, a review is given concerning aspects of epidemiology and prognostic factors of NHL. Therapeutic strategies, including the use of hematopoietic growth factors, for the elderly with aggressive NHL are discussed. The future role for so-called comprehensive geriatric assessment (CGA) to appropriately determine treatment possibilities is emphasized. Much scientific work has to be performed before the true value of CGA instruments can be acknowledged. Screening instruments are discussed and the role for specially trained oncology nurses in the assessment process is stipulated.


Subject(s)
Lymphoma, Non-Hodgkin/epidemiology , Lymphoma, Non-Hodgkin/therapy , Aged , Geriatric Assessment/methods , Hematopoietic Cell Growth Factors/therapeutic use , Humans , Lymphoma, Non-Hodgkin/mortality , Lymphoma, Non-Hodgkin/pathology , Neoplasm Staging , Prognosis , Radioimmunotherapy
20.
Ann Oncol ; 13(8): 1275-84, 2002 Aug.
Article in English | MEDLINE | ID: mdl-12181252

ABSTRACT

BACKGROUND: The influence of age on the outcome of follicular non-Hodgkin's lymphoma (FL) was studied in a population-based non-Hodgkin's lymphoma registry. PATIENTS AND METHODS: This study comprised 214 follicular lymphoma patients. Grade I/II was considered separately from grade III FL. The data were analyzed with respect to three age groups: <60, 60-69 and >or=70 years. RESULTS: The overall survival rate decreased in the older age groups. Grade III patients showed a statistically significant decrease in overall survival in comparison with grade I/II patients (P = 0.03). Cause-specific survival analysis showed that in the older age groups, there was an increasing influence of concomitant disease on the death rate, especially among grade III FL patients >70 years of age. The survival curve in grade III FL patients was shown to reach a plateau. The prognostic scoring system, according to the Italian Lymphoma Intergroup, fitted better to grade I/II patients, while the International Prognostic Index showed better discrimination amongst grade III patients. CONCLUSIONS: Separate grading for follicular lymphoma is useful. An age >70 years has a negative impact on outcome, but the contribution of concomitant disease herein is important. Different prognostic scoring systems should be applied to the different grades of FL.


Subject(s)
Lymphoma, Follicular/epidemiology , Registries , Age Factors , Aged , Cohort Studies , Female , Humans , Incidence , Italy/epidemiology , Lymphoma, Follicular/pathology , Lymphoma, Follicular/therapy , Male , Middle Aged , Neoplasm Staging , Population Surveillance , Prognosis , Prospective Studies , Survival Rate
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