Physician, patient and family attitudes regarding information on prognosis: a Brazilian survey.

BACKGROUND: Communication between physicians and patients is a fundamental aspect of cancer care, yet most physicians' perceptions are often inconsistent with the patients' stated preferences while prognostic information is the most misunderstood. PATIENTS AND METHODS: Members of the Brazilian Society of Oncology Physicians (n=609) were identified and asked to complete a mailed questionnaire. Outpatients (n=150) and their family members (n=150), oncologists and fellows (n=55) from a public healthcare hospital and a tertiary cancer hospital in Sao Paulo were also personally invited to participate. RESULTS: A total of 202 physicians, 150 outpatients and 150 family members were participated. The majority of patients (92%) believe they should know about their terminal stage compared with 79.2% of physicians and 74.7% of families (P=0.0003). Cancer patients were most likely to support disclosure of diagnosis and terminality (P=0.001), to consider that this disclosure was not stressful (P<0.0001) and that this knowledge would improve their quality of life (P<0.0001). CONCLUSIONS: Cancer patients seen in these centers in Southeastern Brazil prefer to know the truth about their poor prognosis more than their physicians and families think. Further studies with larger samples of patients and physicians are necessary to show if our results are representative of all Brazilian situations.

Cancer-related fatigue: a practical review.

Fatigue is an exceedingly common often treatable problem in cancer patients that profoundly affects all aspects of quality of life. Prevalence estimates have ranged from 50% to 90% of cancer patients overall. After addressing reversible or treatable contributing factors, such as hypothyroidism, anemia, sleep disturbance, pain, emotional distress, climacterium, medication adverse events, metabolic disturbances, or organ dysfunction such as heart failure, myopathy, and pulmonary fibrosis, patients may be screened with a brief fatigue self-assessment tool. All cancer patients should be screened regularly for fatigue. Those with moderate or severe fatigue may benefit from both pharmacologic and nonpharmacologic interventions, while mild fatigue that does not interfere with quality of life can be treated with nonpharmacologic measures alone. Physicians often have insufficient knowledge about fatigue and its treatments or underestimate the impact of fatigue on quality of life, while patients may consider it an unavoidable and untreatable side-effect and fear that reporting it may incite a change toward less aggressive cancer treatment. A practical review may therefore be useful to health care professionals in order to avoid the common barriers to its treatment that exist on the sides of both physicians and patients.

Drug interactions in oncology: how common are they?

BACKGROUND: Drug-drug interactions (DDIs) comprise an important problem in medical oncology practice. We systematically reviewed the frequency of DDIs in oncology. METHODS: We searched PubMed for eligible articles and on-line databases for abstracts of major oncology meetings. RESULTS: Eight studies reported on the frequency of DDIs: six evaluated the frequency of potential DDIs, while two studies reported on real DDIs, i.e. interactions that had clinical consequences. Studies of potential DDIs found that approximately one-third of patients are exposed to dangerous drug doublets, with the most common ones involving warfarin and anticonvulsants. One study of real DDIs found that 2% of hospitalized cancer patients had a DDI as the cause of admission. CONCLUSIONS: Drug interactions comprise an important issue in oncology, with approximately one-third of ambulatory cancer patients being at risk of DDIs. Data are limited on the clinical consequences of drug interactions among cancer patients.

XM02 is superior to placebo and equivalent to Neupogen in reducing the duration of severe neutropenia and the incidence of febrile neutropenia in cycle 1 in breast cancer patients receiving docetaxel/doxorubicin chemotherapy.

BACKGROUND: Recombinant granulocyte colony-stimulating factors (G-CSFs) such as Filgrastim are used to treat chemotherapy-induced neutropenia. We investigated a new G-CSF, XM02, and compared it to Neupogen after myelotoxic chemotherapy in breast cancer (BC) patients. METHODS: A total of 348 patients with BC receiving docetaxel/doxorubicin chemotherapy were randomised to treatment with daily injections (subcutaneous 5 microg/kg/day) for at least 5 days and a maximum of 14 days in each cycle of XM02 (n = 140), Neupogen (n = 136) or placebo (n = 72). The primary endpoint was the duration of severe neutropenia (DSN) in cycle 1. RESULTS: The mean DSN in cycle 1 was 1.1, 1.1, and 3.9 days in the XM02, Neupogen, and placebo group, respectively. Superiority of XM02 over placebo and equivalence of XM02 with Neupogen could be demonstrated. Toxicities were similar between XM02 and Neupogen. CONCLUSION: XM02 was superior to placebo and equivalent to Neupogen in reducing DSN after myelotoxic chemotherapy.

Bone and total alkaline phosphatase for screening skeletal metastasis in patients with solid tumours.

Alkaline phosphatase (AP) has several isoforms including bone alkaline phosphatase (BAP). We evaluated BAP and AP for screening for bone metastasis (BM) in patients with solid tumours. This is a prospective non-blinded study conducted at ABC Foundation School of Medicine Oncology clinics. A total of 40 subjects without a history of cancer and 62 patients with various solid tumours referred for a bone scan had serum drawn for BAP and AP determination. Bone alkaline phosphatase and AP levels in patients with cancer and BM, without BM and with no cancer, were 70.32 +/- 3.65 and 310.21 +/- 16.87 U/L; 41.40 +/- 2.80 and 113.23 +/- 12.95 U/L; 21.19 +/- 2.76 and 148.05 +/- 12.79 U/L respectively (P < 0.0001 for both AP and BAP). For BAP and AP sensitivity, specificity, positive and negative predictive values were 0.86 and 0.52; 0.69 and 1; 0.45 and 1; 0.94 and 0.87 respectively. ROC AUC value for BAP was 0.89 and for AP was 0.93. We conclude that BAP is more sensitive than AP, whereas AP had a remarkable specificity of 100%. In screening for BM in patients with solid tumours, obtaining initially BAP and then selecting for further investigation only patients with an abnormal AP may be a cost and resource saving strategy.

Burnout in cancer professionals: a systematic review and meta-analysis.

Burnout syndrome is typified by three dimensions: emotional exhaustion (EE), depersonalization (DP) and low personal accomplishment (PS), and is prevalent among cancer care providers. The objective is to conduct a systematic review and meta-analysis of studies that evaluated the presence of burnout syndrome in professionals dedicated to the care of cancer patients. A search was conducted of the MEDLINE, LILACS and COCHRANE databases. Articles were selected that had used the Maslach questionnaire to assess burnout syndrome prevalence, had evaluated at least 35 subjects (including physicians), had at least a 20% questionnaire response rate, and that were published in English, Spanish or Portuguese. Ten studies (2375 participants) were included in this analysis. Severe involvement by any one of the three dimensions ranged from 8% to 51%. The overall prevalence of EE was found to be 36% [95% confidence interval (CI) (31-41)], while for DP this was 34% [95% CI (30-39)] and for PS 25% [95% CI (0.16-34)], demonstrating considerable heterogeneity across studies. The prevalence of burnout syndrome is elevated among cancer professionals throughout the world but varies substantially among studies. Further research is needed to better understand and prevent this syndrome.

Retinoblastoma protein expression is frequently altered in chronic lymphocytic leukemia.

The detection of abnormalities at the retinoblastoma (RB) locus by cytogenetics, Southern blot, and fluorescence in situ hybridization studies suggests that the RB gene has a role in chronic lymphocytic leukemia (CLL). To further study this role, we determined the level of RB protein present in the mononuclear cell fraction derived from peripheral blood or bone marrow samples from 74 patients with CLL, by Western blotting. Compared to similarly prepared samples from the peripheral blood of normal individuals, the level of RB in CLL cells was less than normal in 42% of patients, equal to normal in 22% of patients, and in excess of normal in 36% of patients. Regardless of whether the source of the sample was blood or marrow or if the patients were untreated or previously treated, similar rates of low, normal, and elevated RB levels were observed. RB protein in the CLL patient samples was never phosphorylated. RB levels showed no correlation with the lymphocyte doubling time or with proliferating cell nuclear antigen levels. Low RB levels could arise from genetic alterations of the RB gene or altered regulation of expression. To determine which was occurring, we stimulated the cells from 27 CLL patients in culture with either phytohemagglutinin or pokeweed mitogen in an attempt to induce RB expression and phosphorylation. Among patients with low levels of RB, expression was induced in 46% (6 of 13), and phosphorylation of RB was seen in 31% (4 of 13). Increased expression of phosphorylated RB was induced in 80% (4 of 5) of patients with normal levels of RB and in 78% (7 of 9) of patients with high levels of RB. This study demonstrates that absent RB expression occurs commonly in patients with CLL. Intrinsic abnormalities of the RB gene may be present in those patients with low levels of RB that could not be stimulated by mitogens, while regulatory abnormalities located in trans to the RB gene may occur in the other half. Given the importance that RB levels play in other cancers, the prognostic implication of low RB levels should be studied in CLL.

Clinical implications of decreased retinoblastoma protein expression in acute myelogenous leukemia.

The retinoblastoma (RB) protein levels in blast-enriched mononuclear fractions from the peripheral blood of 33 newly diagnosed patients with acute myelogenous leukemia were studied. Ten patients who had previously been treated were also analyzed, nine of whom had achieved prior complete remission. Low RB protein expression was found in 13 of 43 (30%) of the acute myelogenous leukemia patients as determined by Western blotting and immunochemical analysis. Of particular interest among the 20 newly diagnosed patients treated with the same therapeutic regimen, the median survival was 39 days for those with low RB protein expression compared to 333 days for those with high levels of RB protein expression in their leukemic cells (P less than or equal to 0.02). This preliminary study suggests that decreases of RB protein expression in peripheral blood of myeloid leukemic cells occur frequently and may be associated with shortened survival of acute myelogenous leukemia patients.

Effect of prior interferon alfa therapy on the outcome of allogeneic bone marrow transplantation for chronic myelogenous leukemia.

PURPOSE: To determine whether prior interferon alfa (IFN-A) treatment affects the outcome of allogeneic bone marrow transplantation. PATIENTS AND METHODS: We analyzed the outcome of 77 patients with chronic myelogenous leukemia (CML) who received transplants from an HLA-identical donor using a total-body irradiation-containing preparative regimen. Engraftment, acute and chronic graft-versus-host disease (GVHD), survival, and disease-free survival were compared between patients who had previously received interferon (IFN+) to those who had not (IFN-). Forty-one patients were transplanted in chronic phase and 36 had more advanced CML. The IFN+ group had received IFN-A in doses of 3 to 5 x 10(6) U/m2 three times a week or more for at least 4 weeks anytime before transplantation. RESULTS: For patients in chronic phase, there were no significant differences between the IFN+ group and the IFN- group in regard to neutrophils recovery more than 1.0 x 10(9)/L (29 v 24), platelet recovery more than 50 x 10(9)/L (33 v 36), incidence of grade II to IV GVHD (23% v 28%), incidence of chronic GVHD (39% v 47%), disease-free survival (46% +/- 11% v 59% +/- 13%), relapse (9% v 11%), or 100-day transplant-related mortality (22% v 16%). In patients with more advanced stage disease, there was also no significant differences between the IFN+ group and the IFN- group in regard to these outcomes. CONCLUSION: Prior treatment with IFN-A did not adversely affect transplant outcome. Further studies are required to better understand the complementary roles of IFN-A and allogeneic bone marrow transplantation for the treatment of CML.

Relevance of the chemical charge of rhodamine dyes to multiple drug resistance.

Previously, we have shown that multiple drug resistant (MDR) Friend leukemia cells (FLC) are cross-resistant to the positively-charged dye, Rhodamine 123 (Rho 123), and that this resistance can be reversed by verapamil (VER). In the present study we used two zwitterionic rhodamine analogs, Rhodamine 116 and Rhodamine 110, and another positively-charged analog, Rhodamine 6G, to determine whether drug accumulation, resistance and modulation were affected by changes in the charge of these compounds. While there was no differential sensitivity between sensitive and resistant FLC to zwitterionic rhodamines, there was marked differential toxicity between these cell types for the positively-charged analogs. The IC50 values were 1000- and 100-fold greater in resistant than in sensitive cells for Rho 123 and Rho 6G respectively. Intracellular drug accumulation was significantly higher in sensitive as compared to resistant cells for both Rho 123 and Rho 6G, but little difference in drug uptake between these two cell types was observed for Rho 110 and Rho 116. It was also found that the intracellular to extracellular ratio of the positively-charged compounds was greater than unity in both sensitive and resistant cells whereas for the zwitterionic analogs this ratio was less than 1. Furthermore, this ratio of drug uptake was found to be significantly higher for Rho 6G than for Rho 123, which correlated with the high oil:water partition coefficient of Rho 6G (115.6). In MDR cells, verapamil increased Rho 123 and Rho 6G accumulation by 9.4- and 8.6-fold respectively. In addition, IC50 values in resistant cells were reduced greater than 100-fold for Rho 6G and greater than 1000-fold for Rho 123 in the presence of 10 micrograms/ml of verapamil. In contrast, less than 2-fold reduction of IC50 values for both of the zwitterionic analogs could be obtained under the same conditions. These results indicate that the chemical charge of rhodamines plays an important role in their differential accumulation, cytotoxicity and sensitivity to modulators such as verapamil, in sensitive and multi-drug resistant cells. The data also suggest that increased lipophilicity of the positively-charged rhodamines may increase their ability to accumulate in, and subsequently kill, MDR cells.

Tumor and serum beta-2-microglobulin expression in women with breast cancer.

To investigate whether the tumor expression of beta-2-microglobulin (beta 2-M) could serve as a marker of tumor biologic behavior, the authors studied specimens of breast carcinomas from 60 consecutive female patients. Presence of beta 2-M was analyzed by immunohistochemistry. No significant correlations were found between tumor beta 2-M expression and several histologic attributes such as type, histologic and nuclear grades, mitotic index, necrosis, vascular invasion, and lymphocytic infiltration. Likewise, beta 2-M was not associated with markers of disease extension such as TNM, (UICC, classification of malignant tumors) staging and axillary lymph node involvement or with estrogen, progesterone, and glucocorticoid receptor levels. However, there was a significantly positive association between tumor beta 2-M expression and the degree of lymphocytic infiltration in the tumor tissue. Beta 2-M serum levels were determined by an enzyme-linked immunosorbent assay in samples from 22 of the above women. Although some of the highest values had been obtained in women with larger (T4) primary tumors, the authors failed to detect any statistical relationship between beta 2-M expression in the tumor with serum levels or between serum beta 2-M and the above histologic, laboratory, and clinical factors.

Quantitative expression of proliferating cell nuclear antigen by western blot (PCNAWB) in peripheral blasts correlates with remission induction in patients with acute myelogenous leukemia.

Proliferating cell nuclear antigen (PCNA) is a 36-kD nuclear protein that functions as a cofactor of delta DNA polymerase which is regulated in a cell cycle-dependent fashion. PCNA expression also increases when cells are actively engaged in DNA repair. We used Western blotting (WB) to measure the level of expression of PCNA in peripheral blasts of 36 adult acute myelogenous leukemia (AML) patients treated with Ara-C based induction regimens. PCNA levels correlated positively with the percentage of cells in S+G2M of the cell cycle. Logistic regression analysis revealed PCNA (beta = 4.5162; p = 0.0260) together with age (beta = 0.1777; p = 0.0364) as independent variables for remission induction: high PCNA levels were associated with poor response to induction therapy. PCNA expression was not, however, a predictor of survival in this subset of patients. We conclude that PCNA levels in this disease may be important for predicting response to Ara-C based remission induction chemotherapy.

Proliferating cell nuclear antigen (PCNA) expression in chronic lymphocytic leukemia (CLL).

Chronic Lymphocytic Leukemia (CLL) is usually an indolent disorder which in some patients assumes an aggressive clinical course. In order to assess at presentation the prognosis of a given patient, several staging systems and prognostic variables have been proposed including the expression of the Proliferating Cell Nuclear Antigen (PCNA). PCNA is a 36 kd nuclear protein, the regulation of which is cell cycle-dependent. In CLL, PCNA levels correlate with cell proliferation, clinical stage and the lymphocyte doubling time (LDT). Furthermore, preliminary data suggests that PCNA expression may also predict response to Fludarabine-based chemotherapy. Since PCNA is a cofactor for Delta DNA polymerase, PCNA overexpression in CLL may also reflect the intrinsic DNA repair activity of the leukemic cells and thus their resistance to chemotherapy. Further studies aiming at modulation of PCNA expression in CLL cells may clarify this issue and may offer a future new therapeutic strategy with which to treat this disorder.

Tuberculous skeletal muscle involvement in acute leukemia: report on two cases.

Bacterial infection of skeletal muscle (pyomyositis) is usually followed by abscess formation. The most commonly isolated pathogen is Staphylococcus aureus. Tuberculosis rarely affects patients with acute leukemia. The authors report on 2 patients, one with acute myelogenous leukemia and the other with acute lymphoblastic leukemia whose clinical course was complicated by tuberculous skeletal muscle abscesses. In both instances, musculoskeletal pain was accompanied by evidence of muscle abscesses by imaging studies of the painful areas. Therefore, in patients with acute leukemia and evidence of muscle abscesses with initial cultures negative for bacteria and fungi, one should include tuberculosis in the differential diagnosis.

[Education via the Internet: preliminary experience of the hematology-oncology discipline of the ABC Foundation School of Medicine]. / Educação via Internet: experiência preliminar de Hematologia e Oncologia da Faculdade de Medicina da Fundação ABC.

BACKGROUND: In order to foster the use of the Internet by our medical students, we devised a virtual test to be taken by the whole class during the Hematology-Oncology course given in the third year. MATERIAL AND METHODS: Through a specially designed home page in the Internet students were asked questions regarding their personal characteristics, knowledge of basic Internet skills and were also given a short virtual course on line on the use of the Internet. RESULTS: We noted that only 53% of our students had used the Internet before. The use of the Internet was correlated with having more members of the household accessing the net (p < 0.001) but not with the student's sex, age or family income. CONCLUSION: Most of the students reacted favourably to this educational experience through which about half of them got acquainted with the use of the Internet for the first time.

[Androgen deprivation therapy and morbid obesity: do they share cardiovascular risk through metabolic syndrome?]. / Terapia de privación de andrógenos y obesidad mórbida: ¿tienenen común el riesgo cardiovascular por síndrome metabólico?

BACKGROUND: Although the use of androgen deprivation therapy (ADT) has resulted in improved survival in men with advanced prostate cancer, the resulting hypogonadism is associated with profound adverse effects comparable to those found in morbid obesity, being cardiovascular risk among the most lethal. OBJECTIVES: Evaluate metabolic syndrome, metabolic abnormalities and cardiovascular risk in patients with prostate cancer under ADT, not under ADT and morbid obese men. METHODS: This is a cross-sectional study that involves 79 men presenting prostate cancer, of whom 54 under ADT and 25 not under ADT and 91 morbidly obese patients paired by sex and age. To define metabolic syndrome, we used the International Diabetes Federation (IDF) criteria. Metabolic abnormalities, metabolic markers and Framingham score to predict the ten year coronary heart disease risk were compared among patients under ADT, not under ADT and morbid obese. RESULTS: Patients under ADT presented significantly greater occurrence of diabetes and central obesity and higher levels of total cholesterol and low density lipoprotein (LDL) compared to eugonadal men. The mean cardiovascular risk was significantly higher in patients under ADT (39.97±12.53% vs. 26.09±14.80%; p=0.021). Morbidly obese subjects had increased ten year coronary heart disease risk; comparable to patients under ADT (p=0.054). CONCLUSION: This study suggests that patients under ADT show higher prevalence of metabolic abnormalities and cardiovascular risk similar to those found in morbidly obese subjects. It is possible that both processes share cardiovascular risk through metabolic syndrome.

XM02, the first granulocyte colony-stimulating factor biosimilar, is safe and effective in reducing the duration of severe neutropenia and incidence of febrile neutropenia in patients with non-Hodgkin lymphoma receiving chemotherapy.

Recombinant granulocyte colony-stimulating factors (G-CSFs) such as filgrastim or lenograstim are being used to treat chemotherapy-induced neutropenia. The aim of the present study was to investigate a new G-CSF, XM02, in comparison to filgrastim in terms of safety and efficacy in the prevention of chemotherapy-induced neutropenia in non-Hodgkin-lymphoma (NHL). A total of 92 patients receiving chemotherapy were randomised in cycle 1 to treatment with daily injections (subcutaneous 5 microg/kg/day) of XM02 (n = 63) or filgrastim (n = 29) for at least 5 days and a maximum of 14 days. In subsequent cycles, all patients received XM02. The mean duration of severe neutropenia (DSN) was 0.5 and 0.9 days in cycle 1 for XM02 and filgrastim, respectively (p = 0.1055). In cycle 1, the incidence of febrile neutropenia (FN) was 11.1% for XM02 and 20.7% for filgrastim (p = 0.1232). The adverse event profile was similar between XM02 and filgrastim. XM02 demonstrated equivalent efficacy and similar safety profile as the reference medication filgrastim. Treatment with XM02 is as beneficial as filgrastim in ameliorating severe neutropenia and FN in patients with NHL receiving chemotherapy. XM02 is safe and well tolerated in the doses applied in this study.

An open-label, fixed-dose study of bupropion effect on sexual function scores in women treated for breast cancer.

BACKGROUND: Sexual morbidity after chemotherapy and hormonal therapy for breast cancer can seriously affect patients' quality of life. Bupropion is an antidepressant that has been reported to increase libido. OBJECTIVE: To investigate the improvement of sexual function in female breast cancer patients using bupropion. PATIENTS AND METHODS: We performed an 8-week open trial using bupropion in women diagnosed with breast cancer who had received chemotherapy and were currently receiving adjunctive hormonal therapy. The Arizona Sexual Experience Scale (ASEX) was used. The ASEX scale includes five questions that evaluate sexual function in the following areas: libido, excitability and ability to reach orgasm. Women received oral Bupropion 150 mg/daily for 8 weeks and were evaluated prior to the initiation of the study and again during Weeks 4 and 8. RESULTS: Twenty patients were included in the study. At the beginning of the study, the mean ASEX score was 23.45 [21.67-25.24] 95% CI. After 4 weeks of treatment, we observed a reduction in the mean ASEX score that persisted until the end of the study, at eight weeks: 18.45 [16.59-20.31] 95% CI (P = 0.0003) and 18.95 [16.60-21.30] 95% CI (P = 0.0024), respectively. CONCLUSION: In this non-controlled open trial bupropion 150 mg/daily was associated with improved sexual function in women receiving adjuvant systemic treatment for breast cancer.

Randomized crossover trial of intravenous 5-FU versus oral UFT both modulated by leucovorin: a one-centre experience.

Although intravenous (IV) 5-fluorouracil (5-FU) and uracil/futraful (UFT) have comparable antitumour efficacy in the treatment of metastatic colorectal cancer (MCC), we wanted to assess which of these two regimens would be preferred by our patients. We randomized 20 previously untreated patients with MCC at our centre to receive oral UFT or bolus IV 5-FU both associated with leucovorin. After the first cycle patients were crossed over to the other arm. Before the third cycle we left patients to choose one of the regimens to continue their treatment until disease progression. Two patients chose 5-FU and 18 chose UFT (P < 0.001). Fewer side effects (50%) and convenience of home treatment (40%) were the main reasons for their choice for the oral regimen. UFT induced less mucositis (P = 0. 02) and diarrhoea (P = 0. 01). We conclude that convenience and lower toxicity may explain the observed preference for oral UFT.