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BACKGROUND: Human epidermal growth factor 2 (HER2) is an effective therapeutic target in breast cancer; however, resistance to anti-HER2 agents such as trastuzumab and lapatinib develops. In a preclinical model, an HDAC inhibitor epigenetically reversed the resistance of cancer cells to trastuzumab and showed synergistic efficacy with lapatinib in inhibiting growth of trastuzumab-resistant HER2-positive (HER2+) breast cancer. METHODS: A phase 1b, dose escalation study was performed to assess maximum tolerated dose, safety/toxicity, clinical efficacy and explored pharmacodynamic biomarkers of response to entinostat combined with lapatinib with or without trastuzumab. RESULTS: The combination was safe. The MTD was lapatinib, 1000 mg daily; entinostat, 12 mg every other week; trastuzumab, 8 mg/kg followed by 6 mg/kg every 3 weeks. Adverse events included diarrhoea (89%), neutropenia (31%), and thrombocytopenia (23%). Neutropenia, thrombocytopenia and hypokalaemia were noted. Pharmacodynamic assessment did not yield conclusive results. Among 35 patients with evaluable response, PR was observed in 3 patients and CR in 3 patients, 1 maintained SD for over 6 months. DISCUSSION: This study identified the MTD of the entinostat, lapatinib, and trastuzumab combination that provided acceptable tolerability and anti-tumour activity in heavily pre-treated patients with HER2+ metastatic breast cancer, supporting a confirmatory trial.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/enzimologia , Receptor ErbB-2/metabolismo , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Benzamidas/administração & dosagem , Benzamidas/efeitos adversos , Neoplasias da Mama Masculina/tratamento farmacológico , Neoplasias da Mama Masculina/enzimologia , Relação Dose-Resposta a Droga , Resistencia a Medicamentos Antineoplásicos , Sinergismo Farmacológico , Feminino , Humanos , Lapatinib/efeitos adversos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Piridinas/administração & dosagem , Piridinas/efeitos adversos , Taxa de Sobrevida , Trastuzumab/administração & dosagem , Trastuzumab/efeitos adversosRESUMO
Circulating tumor cells (CTCs) are indicators of metastatic spread and progression. In a longitudinal, single-center trial of patients with metastatic breast cancer starting a new line of treatment, a microcavity array was used to enrich CTCs from 184 patients at up to 9 timepoints at 3-month intervals. CTCs were analyzed in parallel samples from the same blood draw by imaging and by gene expression profiling to capture CTC phenotypic plasticity. Enumeration of CTCs by image analysis relying primarily on epithelial markers from samples obtained before therapy or at 3-month follow-up identified the patients at the highest risk of progression. CTC counts decreased with therapy, and progressors had higher CTC counts than non-progressors. CTC count was prognostic primarily at the start of therapy in univariate and multivariate analyses but had less prognostic utility at 6 months to 1 year later. In contrast, gene expression, including both epithelial and mesenchymal markers, identified high-risk patients after 6-9 months of treatment, and progressors had a shift towards mesenchymal CTC gene expression on therapy. Cross-sectional analysis showed higher CTC-related gene expression in progressors 6-15 months after baseline. Furthermore, patients with higher CTC counts and CTC gene expression experienced more progression events. Longitudinal time-dependent multivariate analysis indicated that CTC count, triple-negative status, and CTC expression of FGFR1 significantly correlated with inferior progression-free survival while CTC count and triple-negative status correlated with inferior overall survival. This highlights the utility of protein-agnostic CTC enrichment and multimodality analysis to capture the heterogeneity of CTCs.
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BACKGROUND: Numerous studies have demonstrated that expression of estrogen/progesterone receptor (ER/PR) and human epidermal growth factor receptor (HER)-2 is important for predicting overall survival (OS), distant relapse (DR), and locoregional relapse (LRR) in early and advanced breast cancer patients. However, these findings have not been confirmed for inflammatory breast cancer (IBC), which has different biological features than non-IBC. METHODS: We retrospectively analyzed the records of 316 women who presented to MD Anderson Cancer Center in 1989-2008 with newly diagnosed IBC without distant metastases. Most patients received neoadjuvant chemotherapy, mastectomy, and postmastectomy radiation. Patients were grouped according to receptor status: ER(+) (ER(+)/PR(+) and HER-2-; n = 105), ER(+)HER-2(+) (ER(+)/PR(+) and HER-2(+); n = 37), HER-2(+) (ER(-)/PR(-) and HER-2(+); n = 83), or triple-negative (TN) (ER(-)PR(-)HER-2(-); n = 91). Kaplan-Meier and Cox proportional hazards methods were used to assess LRR, DR, and OS rates and their associations with prognostic factors. RESULTS: The median age was 50 years (range, 24-83 years). The median follow-up time and median OS time for all patients were both 33 months. The 5-year actuarial OS rates were 58.7% for the entire cohort, 69.7% for ER(+) patients, 73.5% for ER(+)HER-2(+) patients, 54.0% for HER=2(+) patients, and 42.7% for TN patients (p < .0001); 5-year LRR rates were 20.3%, 8.0%, 12.6%, 22.6%, and 38.6%, respectively, for the four subgroups (p < .0001); and 5-year DR rates were 45.5%, 28.8%, 50.1%, 52.1%, and 56.7%, respectively (p < .001). OS and LRR rates were worse for TN patients than for any other subgroup (p < .0001-.03). CONCLUSIONS: TN disease is associated with worse OS, DR, and LRR outcomes in IBC patients, indicating the need for developing new locoregional and systemic treatment strategies for patients with this aggressive subtype.
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Neoplasias Inflamatórias Mamárias , Metástase Neoplásica , Recidiva Local de Neoplasia/química , Receptores de Estrogênio/análise , Receptores de Progesterona/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Receptores ErbB/genética , Feminino , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Neoplasias Inflamatórias Mamárias/química , Neoplasias Inflamatórias Mamárias/diagnóstico , Neoplasias Inflamatórias Mamárias/genética , Neoplasias Inflamatórias Mamárias/mortalidade , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND: To date, studies on inflammatory breast cancer (IBC) lack comprehensive epidemiological data. We analyzed detailed prospectively collected clinical and epidemiological data from the IBC Registry at The University of Texas MD Anderson Cancer Center. METHODS: Patients with IBC (n = 248) were consecutively diagnosed and prospectively enrolled between November 2006 and April 2013. All patients were newly diagnosed and at least 18 years old. Secondary IBC was excluded. Overall 160 variables were collected and evaluated including sociodemographics, anthropometrics, tobacco and alcohol consumption, reproductive variables, and family history data. RESULTS: Mean age at diagnosis was 51.6 (±11.5 SD) years, and the majority of patients were White (77.8%). A mean BMI ≥ 25 kg/m2, irrespective of menopausal status, was observed in 80.2% of all patients, with 82.6% of African Americans being obese. Approximately 42.2% of patients were ever smokers, and 91% reported ever being pregnant. A history of breastfeeding was reported in 54% of patients, with significant differences between ethnic groups in favor of White women (P<0.0001). Other reproductive factors such as use of birth control pills & hormone replacement therapy were also more frequently associated with White women compare to other ethnic groups (P < 0.05). In the multivariate Cox proportional hazard analysis, African American or Hispanic ethnicity, not having breastfed, higher clinical stage, and TNBC subtype were associated with shorter survival. CONCLUSION: Our data suggest that IBC is associated with distinct epidemiological profiles. This information could assist in targeting patients with specific preventive strategies based on their modifiable behavioral patterns.
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Neoplasias Inflamatórias Mamárias/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Neoplasias Inflamatórias Mamárias/patologia , Pessoa de Meia-Idade , Estudos Prospectivos , Sistema de Registros , Fatores de Risco , Análise de Sobrevida , Adulto JovemRESUMO
Importance: Combining conventional chemotherapy with targeted therapy has been proposed to improve the pathologic complete response (pCR) rate in patients with inflammatory breast cancer (IBC). Epidermal growth factor receptor (EGFR) expression is an independent predictor of low overall survival in patients with IBC. Objective: To evaluate the safety and efficacy of the anti-EGFR antibody panitumumab plus neoadjuvant chemotherapy in patients with primary human epidermal growth factor receptor 2 (HER2)-negative IBC. Design, Setting, and Participants: Women with primary HER2-negative IBC were enrolled from 2010 to 2015 and received panitumumab plus neoadjuvant chemotherapy. Median follow-up time was 19.3 months. Tumor tissues collected before and after the first dose of panitumumab were subjected to immunohistochemical staining and RNA sequencing analysis to identify biomarkers predictive of pCR. Intervention: Patients received 1 dose of panitumumab (2.5 mg/kg) followed by 4 cycles of panitumumab (2.5 mg/kg), nab-paclitaxel (100 mg/m2), and carboplatin weekly and then 4 cycles of fluorouracil (500 mg/m2), epirubicin (100 mg/m2), and cyclophosphamide (500 mg/m2) every 3 weeks. Main Outcomes and Measures: The primary end point was pCR rate; the secondary end point was safety. The exploratory objective was to identify biomarkers predictive of pCR. Results: Forty-seven patients were accrued; 7 were ineligible. The 40 enrolled women had a median age of 57 (range, 23-68) years; 29 (72%) were postmenopausal. Three patients did not complete therapy because of toxic effects (n = 2) or distant metastasis (n = 1). Nineteen patients had triple-negative and 21 had hormone receptor-positive IBC. The pCR and pCR rates were overall, 11 of 40 (28%; 95% CI, 15%-44%); triple-negative IBC, 8 of 19 (42%; 95% CI, 20%-66%); and hormone receptor-positive/HER2-negative IBC, 3 of 21 (14%; 95% CI, 3%-36%). During treatment with panitumumab, nab-paclitaxel, and carboplatin, 10 patients were hospitalized for treatment-related toxic effects, including 5 with neutropenia-related events. There were no treatment-related deaths. The most frequent nonhematologic adverse event was skin rash. Several potential predictors of pCR were identified, including pEGFR expression and COX-2 expression. Conclusions and Relevance: This combination of panitumumab and chemotherapy showed the highest pCR rate ever reported in triple-negative IBC. A randomized phase 2 study is ongoing to determine the role of panitumumab in patients with triple-negative IBC and to further validate predictive biomarkers. Trial Registration: ClinicalTrials.gov Identifier: NCT01036087.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Panitumumabe/uso terapêutico , Adulto , Idoso , Alopecia/induzido quimicamente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/metabolismo , Quimioterapia Adjuvante , Intervalo Livre de Doença , Quimioterapia Combinada , Fadiga/induzido quimicamente , Feminino , Humanos , Leucopenia/induzido quimicamente , Pessoa de Meia-Idade , Terapia Neoadjuvante , Panitumumabe/administração & dosagem , Panitumumabe/efeitos adversos , Receptor ErbB-2/metabolismo , Adulto JovemRESUMO
Management of symptomatic infections can aid in palliation. We investigated the pharmacokinetics and tolerability of cefepime given as a subcutaneous infusion. This novel route of administration is proposed as an alternative to intravenous and intramuscular administration for patients treated outside an institutional setting, such as home hospice. Ten healthy adult volunteers received a single dose of 1g cefepime infused subcutaneously over 30 minutes. Serial serum samples (0.5, 1, 1.5, 2, 4, 6, 9, and 12 hours) were obtained after the end of infusion, and cefepime concentrations were determined by high performance liquid chromatography (HPLC). All serum concentration profiles were modeled by a population pharmacokinetic analysis using the Non-Parametric Adaptive Grid (NPAG) program. Acceptability of administration was evaluated using subjective sensation grading, observation of the subcutaneous site, and a final global evaluation. The mean (median) Cmax, beta-t1/2, AUC0-oo and total clearance were found to be 36.1 (30.9) mg/L, 2.34 (2.56) hours, 134.8 (125.3) h*mg/L, and 7.42 (7.98) L/h, respectively. All infusions were completed without difficulty or discomfort. No drug side effects occurred. The global acceptability was "strongly agreeable" with all the subjects. Subcutaneous infusion of cefepime appeared to result in a pharmacokinetic profile similar to that of an intramuscular injection. Our evaluations showed excellent tolerability and acceptability. These favorable results warrant further clinical evaluation.
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Cefalosporinas/administração & dosagem , Cefalosporinas/farmacocinética , Adulto , Cefepima , Feminino , Humanos , Infusões Parenterais , Masculino , Pessoa de Meia-Idade , Valores de Referência , Tela SubcutâneaRESUMO
BACKGROUND: Inflammatory breast cancer is a rare and aggressive presentation of breast cancer. Bone is a common metastatic site in breast cancer, and bone-only metastatic disease is clinically considered to have a better prognosis than visceral metastasis. However, bone-only metastasis in IBC (bone-only IBC) has not been compared with bone-only metastasis in non-IBC (bone-only non-IBC) in terms of clinical features and outcome. Because of the intrinsically aggressive nature of IBC, we hypothesized that bone-only IBC has a poorer prognosis than does bone-only non-IBC. PATIENTS AND METHODS: We retrospectively identified patients with stage III primary diagnosed breast cancer who, between January 1997 and December 2012, had a first recurrence located only in the bone. Among the 197 patients that we defined as a study cohort, 50 patients had IBC and 147 patients had non-IBC. Progression-free survival (PFS) and overall survival (OS) from the date of recurrence were estimated using the Kaplan-Meier method, and patient characteristic groups were compared using the log-rank test. RESULTS: OS did not differ significantly between the 2 groups (P = .2467), but a shorter PFS was seen in patients with bone-only IBC than in patients with bone-only non-IBC (P = .0357). Among patients with estrogen receptor (ER)-positive disease, a much shorter PFS was seen in bone-only IBC than in bone-only non-IBC (P = .0159). CONCLUSION: Bone-only IBC has a poorer prognosis than does bone-only non-IBC, particularly in those with ER-positive tumors. We might need to consider more aggressive intervention (e.g., chemotherapy) for IBC patients with ER-positive bone-only metastatic disease.
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Neoplasias Ósseas/secundário , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Neoplasias Inflamatórias Mamárias/diagnóstico , Neoplasias Inflamatórias Mamárias/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/mortalidade , Neoplasias da Mama/mortalidade , Feminino , Humanos , Neoplasias Inflamatórias Mamárias/mortalidade , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Estudos Retrospectivos , Análise de SobrevidaRESUMO
The majority of cancer patients wish to die at home. Improved understanding of place of death and its relevant demographic predictors is important for the planning of palliative cancer care programs. The purpose of this study was to determine the place and predictors of site of death in cancer patients in a major U.S. metropolitan area. Death certificate data over two years were analyzed for Houston area residents with cancer who died in the Houston area. Information was obtained on factors that might be associated with the place where cancer patients die. For the purpose of this study, we looked at the following variables: primary site of cancer (hematological, breast, genitourinary, gastrointestinal, lung, and other); black, white, Hispanic, or Asian; age at death; marital status; sex; whether or not veteran of U.S. armed forces; levels of education; and area of residency within the Houston area. Univariate and multivariate analyses were performed. The majority of patients died in the hospital (51-52% both years), with the next most frequently occurring group dying at home (34-35% both years). Stepwise multivariate analysis resulted in a 6-variable logistic regression model. In this model, the odds of dying in hospital were increased by a factor of 2.7 if the patient had a hematological cancer (P<0.0001), a factor of 1.6 if the patient lived in Harris County (P<0.0001), and a factor of 1.5 if the patient was black (P<0.0001). Further characterization of factors associated with increased risk of hospital death rate is needed and systems should be developed to enable the majority of cancer patients to access palliative care services in the multiple settings in which they die.
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Serviços de Assistência Domiciliar/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Neoplasias/mortalidade , Cuidados Paliativos/estatística & dados numéricos , Idoso , Atestado de Óbito , Feminino , Humanos , Modelos Logísticos , Masculino , Texas/epidemiologia , População Urbana/estatística & dados numéricosRESUMO
OBJECTIVES: To determine the effects of thalidomide and placebo on anorexia-cachexia and its related symptoms, body composition, resting metabolic rate, and serum cytokines and their receptors in patients with advanced cancer. METHODS: Included in the study were patients with advanced cancer with weight loss greater than 5% in 6 months and who reported anorexia, fatigue, and one of the following: anxiety, depression, or sleep disturbances. Patients on chemotherapy within 2 weeks prior or during the study were excluded from the study. Patients were randomly assigned to either 100 mg thalidomide or placebo once a day for 14 days. The Edmonton Symptom Assessment Scale (ESAS), Functional Assessment of Anorexia/Cachexia Therapy (FAACT), Functional Assessment of Cancer Illness Therapy (FACIT-F), Hospital Anxiety Depression Scale (HADS) Pittsburgh Sleep Quality Index (PSQI) were utilized, and in addition body composition, Resting Energy Expenditure (REE), and serum cytokine levels were assessed. RESULTS: Of the 31 patients entered in the study, 15 were assigned to the thalidomide group and 16 to the placebo group. However only 21/31 patients were able to complete the study. Compared with their baseline values, both the thalidomide and the placebo groups showed significant reduction in cytokines. Tumor necrosis factor (TNF)-α (p=0.04) and its receptors TNFR1 (p=0.04), TNFR2 (p=0.04), and interleukin (IL)-8 (p=0.04) were statistically significant in the thalidomide group. In the placebo group, TNF-α (p=0.008), TNFR1 (p=0.005), TNFR2 (p=0.005), IL-RA (p=0.005), IL-6 (p=0.005), and IL-8 (p=0.005) were statistically significant. However, improvement in these symptoms and cytokine levels were not significantly different in the thalidomide group compared with the placebo group. None of the patients withdrew from the study because of toxicity of either thalidomide or placebo. CONCLUSIONS: Based on the poor accrual rate and attrition observed in this study, it is important that future research on thalidomide as a treatment for cancer-related anorexia-cachexia symptoms (ACS) in patients with advanced cancer use less stringent entry criteria and less exhaustive outcome measures.
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Anorexia/tratamento farmacológico , Caquexia/tratamento farmacológico , Imunossupressores/uso terapêutico , Neoplasias/complicações , Talidomida/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anorexia/etiologia , Caquexia/etiologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/patologia , Texas , Adulto JovemRESUMO
BACKGROUND: The objective of this study was to determine whether hypogonadism and autonomic dysfunction contribute substantially to cancer-related fatigue, decreased sexual desire, and depression in male patients with advanced, incurable cancer. METHODS: Forty-eight patients who had received no major antineoplastic intervention for at least 2 weeks were tested for autonomic dysfunction by using Ewing tests. Total and free testosterone levels were measured. Multivariate analyses were performed to test the relation of these factors with the Functional Assessment of Cancer Therapy (FACT) (the Functional Assessment of Anorexia/Cachexia Therapy [FAACT] scale and the Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-F] subscale), the Hospital Anxiety and Depression Scale (HADS), the Edmonton Symptom Assessment Scale, the Sexual Desire Inventory, and sexual function (Cancer Rehabilitation Evaluation System subscale). Common causes for fatigue (anemia, depression, malnutrition, symptom distress, and medications) also were considered. RESULTS: Thirty-eight of 47 patients (81%) had autonomic dysfunction, although it was not associated significantly with the other variables examined. Twenty-nine of 45 patients (64%) had a low level of free testosterone (hypogonadism), which was correlated with the HADS Anxiety score (P = .002), the FACT Emotional Well-Being score (P = .02), and the HADS Depression score (P = .04). Hypogonadal men also had lower scores on the FACT Functional Well-Being scale (P = .01) and the FACIT-F subscale (P = .05). Men who reported symptoms related to weight loss (FAACT scale) had significantly lower levels of free testosterone (r = 0.34; P = .02) but did not differ from the other group in actual weight loss (P = .22). The total testosterone level was not appropriate for screening of hypogonadism unless the patients had values <100 ng/ mL. Logistic regression analysis failed to reveal a distinct multivariate model of autonomic dysfunction or hypogonadism that predicted clinical outcomes. CONCLUSIONS: Hypogonadism is a frequent condition in patients with advanced, incurable cancer and is associated with negative mood, fatigue, and symptoms related to anorexia/cachexia.
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Sintomas Afetivos/etiologia , Doenças do Sistema Nervoso Autônomo/complicações , Fadiga/etiologia , Hipogonadismo/complicações , Neoplasias/complicações , Disfunções Sexuais Psicogênicas/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Emoções , Humanos , Masculino , Pessoa de Meia-Idade , Projetos PilotoRESUMO
OBJECTIVE: To evaluate the specificity, sensitivity, and accuracy of pain intensity assessments (0-10) conducted by registered nurses (RN) and clinical nurse assistants (CAN) as compared to those conducted by the palliative care consultant (PCC). PATIENTS AND METHODS: We performed a retrospective review of charts of patients who had received palliative care consult between April 2002 and August 2002. Data on patient demographic, date of palliative care consult, and date and intensity of pain assessment were collected. A numerical rating scale from 0 (no pain) to 10 (worst pain) was used to assess pain intensity. The data were included for analysis if the pain intensity assessment was performed during the same shift by all three care providers (RN, CNA, and PCC). RESULTS: Forty-one charts were found to include a complete pain assessment performed by the RN, CNA, and PCC. The agreement of pain intensity between the PCC and both the RN and CNA was poor. For a diagnosis of moderate-to-severe pain, the RN's intensity assessment had a specificity of 90% but a sensitivity of 45%, and the CNA's intensity assessment had a specificity of 100% but a sensitivity of only 30%. The Spearman correlation coefficient between the intensity assessments performed by the PCC and the RN was 0.56 (p=0.00) and between those by the PCC and the CNA 0.22 (p=0.15). CONCLUSION: Lack of agreement between pain intensity assessments performed by the PCC and bedside nurse suggests possible inconsistencies in the way the assessments were performed. Better education on how to perform standard pain intensity assessment is needed.
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Consultores , Recursos Humanos de Enfermagem Hospitalar , Medição da Dor , Dor/fisiopatologia , Cuidados Paliativos , Quartos de Pacientes , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Dor/etiologia , Estudos Retrospectivos , Sensibilidade e Especificidade , TexasRESUMO
BACKGROUND: Patient autonomy and participation in treatment decision making have been encouraged in recent years. However, patients and physicians frequently disagree with regard to the patient's needs and perceptions of their illness. To the authors' knowledge to date only limited research has assessed physicians' perceptions of patients' decision-making preferences. The purpose of the current prospective study was to determine the agreement between patient decision-making preferences and physician perceptions of those preferences. METHODS: Women with breast carcinoma who were attending their first outpatient consultation with a breast medical oncologist in a university cancer center were enrolled in the current study. At the end of the consultation, the patients were given a survey regarding their treatment decision-making preferences that included active, shared, and passive roles in decision-making and the patients' attending physicians also were given a survey regarding their perceptions of the patients' decision-making preferences. RESULTS: Fifty-seven patients had complete data and were analyzed. Approximately 89% of these 57 patients preferred either an active or a shared role in decision making. The agreement between patients and physicians with regard to decision-making preference only occurred in 24 cases (42%). The majority of covariates such as age, education, and income were not found to be statistically significant with regard to patient preferences or to the proportion of patients and physicians who agreed on the patient's preferences. CONCLUSIONS: Women with breast carcinoma appear to have a strong desire for involvement in making decisions regarding their treatment. However, physicians do not appear to be consistently able to predict the decision-making preferences of their patients. Enhanced agreement between patient preferences and physician expectations mostly likely will improve communication and patient satisfaction with the treatment decision-making process.
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Neoplasias da Mama/psicologia , Neoplasias da Mama/terapia , Participação do Paciente/psicologia , Satisfação do Paciente , Médicos/psicologia , Atitude do Pessoal de Saúde , Tomada de Decisões , Feminino , Inquéritos Epidemiológicos , Humanos , Pessoa de Meia-Idade , Autonomia Pessoal , Relações Médico-Paciente , Estudos ProspectivosRESUMO
BACKGROUND: Flu-like symptoms are common, early transient side effects of paclitaxel chemotherapy. We hypothesized that these symptoms may be due to release of inflammatory cytokines in response to treatment. The objective of this study was to assess changes in plasma levels of interleukin (IL)-1beta, IL-6, IL-8, IL-10, IL-12, and TNF-alpha during chemotherapy and to correlate these changes with musculoskeletal symptoms. METHODS: Ninety patients with breast cancer were included; 70 patients received single agent paclitaxel either weekly or every 3 weeks and 20 received FAC (5-FU, doxorubicin, cyclophosphamide) chemotherapy. Fifteen healthy volunteers were included as controls. Cytokines and symptoms were measured before starting therapy, on day 3 and on the last day of one treatment cycle. RESULTS: At baseline, all subjects had measurable levels of IL-8 but only 49% had IL-12, 45% had IL-10, 32% had IL-6, and 21% had IL-1beta or TNF-alpha in their plasma. There was no difference in baseline cytokine levels between cancer patients and the healthy volunteers. Schedule-dependent transient changes in the levels of 3 cytokines were observed in the paclitaxel treated patients. In the every 3-week paclitaxel group, IL-6 and IL-8 increased whereas in the weekly paclitaxel group IL-10 increased significantly compared to baseline. Fatigue and flu-like symptoms were also worse on day 3. In the weekly paclitaxel group, increase in IL-10 level correlated positively with joint pain (p=0.003). In the every 3-week paclitaxel group, increase in IL-8 level correlated positively with flu-like symptom (p=0.008). In the FAC-treated group and among the healthy volunteers none of these cytokines increased significantly. CONCLUSIONS: Weekly paclitaxel induces transient increase in IL-10 levels whereas every 3-week higher dose treatments induce IL-8 and IL-6 in the plasma. These changes correlate with joint pain and flu-like symptoms.