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1.
Ann Oncol ; 25(1): 210-5, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24356632

RESUMO

BACKGROUND: Marginal zone lymphoma (MZL) is a non-Hodgkin lymphoma that occurs as extra nodal, nodal, or splenic. While MZL is generally considered an indolent disease, a substantial percentage of patients follow an unfavorable course. The objective of this retrospective analysis was to identify predictors for a reduced overall survival (OS), or conversely an increased OS. PATIENTS AND METHODS: One hundred and ninety-seven MZL patients were analyzed. Apart from assessing previously published risk factors, concomitant morbidity at diagnosis, transformation into aggressive lymphoma, and occurrence of additional malignancies were evaluated. RESULTS: Next to the known risk factors, i.e. above 60 years of age and elevated serum lactate dehydrogenase (LDH), we demonstrate that transformation into aggressive lymphoma, as well as additional malignancies, are important independent risk factors for a shortened OS in a multivariate analysis, irrespective of the MZL localization. Impressively, in the group of patients lacking LDH elevation, transformation, and/or additional malignancies, only 1 of 63 patients died during follow-up compared with 37 of 87 patients in the high-risk group (HR = 22.8; 95% confidence interval 3.1-167.0; P = 0.002). CONCLUSIONS: Our analysis proposes novel risk factors and warrants for a continuous follow-up to detect the occurrence of transformation and additional malignancies early on.


Assuntos
Linfoma de Zona Marginal Tipo Células B/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Transformação Celular Neoplásica/metabolismo , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , L-Lactato Desidrogenase/sangue , Linfoma de Zona Marginal Tipo Células B/sangue , Linfoma de Zona Marginal Tipo Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Fatores de Risco , Resultado do Tratamento , Adulto Jovem
2.
Ann Oncol ; 25(1): 95-100, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24276026

RESUMO

BACKGROUND: Early detection and improved (neo)-adjuvant treatment has extended survival of breast cancer over the last decades. It remains controversial whether a survival benefit is achieved once metastases have occurred. This study investigates survival trends in metastatic breast cancer (MBC) looking at the distribution of prognostic factors and the time period of the diagnosis of the primary and metastatic disease. PATIENTS AND METHODS: In this retrospective study, 1635 patients, diagnosed with MBC and treated at three German cancer centers, were included. For the survival analysis, patients were grouped into three time periods [1980-1994 (a), 1995-1999 (b) and 2000-2009 (c)], which were chosen according to the availability of new antineoplastic drugs for the treatment of MBC. Additionally, patients were divided into three risk groups using the simultaneously published prognostic score. RESULTS: The analysis of overall survival according to the date of primary diagnosis demonstrated a significant decline compared with the reference (a): (a versus b) hazard ratio (HR) = 1.37; P < 0.001; (a versus c) HR = 2.45; P < 0.001. Considering the time of first occurrence of metastasis, survival remains unchanged over the three periods (a versus b): HR = 0.94 P = 0.436; (a versus c): HR = 0.95; P = 0.435. However, a significant shift towards more unfavorable risk factors was seen. CONCLUSIONS: Although survival in MBC remains unchanged over time, patients developing metastatic disease have a more aggressive disease that is presumably compensated by more effective treatment. This alteration of tumor biology in MBC may be explained by a negative selection of patients with adverse risk profiles due to the advantages of the adjuvant therapy.


Assuntos
Neoplasias Ósseas/mortalidade , Neoplasias da Mama/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/secundário , Neoplasias Ósseas/terapia , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Adulto Jovem
3.
Ann Oncol ; 25(3): 633-638, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24368402

RESUMO

BACKGROUND: The prognosis of metastatic breast cancer (MBC) is extremely heterogeneous. Although patients with MBC will uniformly die to their disease, survival may range from a few months to several years. This underscores the importance of defining prognostic factors to develop risk-adopted treatment strategies. Our aim has been to use simple measures to judge a patient's prognosis when metastatic disease is diagnosed. PATIENTS AND METHODS: We retrospectively analyzed 2269 patients from four clinical cancer registries. The prognostic score was calculated from the regression coefficients found in the Cox regression analysis. Based on the score, patients were classified into high-, intermediate-, and low-risk groups. Bootstrapping and time-dependent receiver operating characteristic curves were used for internal validation. Two independent datasets were used for external validation. RESULTS: Metastatic-free interval, localization of metastases, and hormone receptor status were identified as significant prognostic factors in the multivariate analysis. The three prognostic groups showed highly significant differences regarding overall survival from the time of metastasis [intermediate compared with low risk: hazard ratio (HR) 1.76, 95% confidence interval (CI) 1.36-2.27, P < 0.001; high compared with low risk: HR 3.54, 95% CI 2.81-4.45, P < 0.001). The median overall survival in these three groups were 61, 38, and 22 months, respectively. The external validation showed congruent results. CONCLUSIONS: We developed a prognostic score, based on routine parameters easily accessible in daily clinical care. Although major progress has been made, the optimal therapeutic management of the individual patient is still unknown. Besides elaborative molecular classification of tumors, simple clinical measures such as our model may be helpful to further individualize optimal breast cancer care.


Assuntos
Neoplasias da Mama/mortalidade , Recidiva Local de Neoplasia/mortalidade , Avaliação de Resultados em Cuidados de Saúde , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/terapia , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Gradação de Tumores , Metástase Neoplásica , Análise de Regressão , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
4.
Breast Cancer Res Treat ; 136(3): 789-94, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23124416

RESUMO

Depression and anxiety are the core disorders causing emotional distress in patients (pts) with metastatic breast cancer. The aim of our study was to screen metastatic breast cancer outpatients for anxiety and depression, and to investigate the influence of age, Karnofsky Performance Status (KPS), cancer activity, and inflammation as represented by IL-6 levels on these two mood disorders. Pts treated with chemotherapy for metastatic breast cancer (n = 70) were assessed using the Hospital Anxiety and Depression Scale (HADS) for symptoms (scores 0-21) and caseness (score ≥11) of clinical depression and anxiety. Blood samples for IL-6 concentrations were collected at 10:00 a.m. A total of 22 (31.4 %) pts were diagnosed with caseness of clinical depression and 23 (32.9 %) pts with clinical anxiety, while 12 pts were diagnosed positive for both mood disorders. Depression and anxiety were positively but moderately correlated (Spearman's r (2) = 0.24, p < 0.001). IL-6 was significantly correlated with symptoms of depression (r (2) = 0.42, p < 0.001) and to a lesser extent to symptoms of anxiety (r (2) = 0.16, p = 0.001). In addition, IL-6 was positively associated with tumor progression (p < 0.001). Multiple linear regression analysis showed that tumor progression (standardized b = 0.226, p = 0.047), symptoms of anxiety (b = 0.292, p = 0.016), and IL-6 (b = 0.314, p = 0.007) were independently associated with clinical depression, whereas anxiety was linked to tumor progression (b = 0.238, p = 0.030), symptoms of depression (b = 0.407, p < 0.001) and age (b = -0.381, p < 0.001), but not to IL-6 (b = 0.168, p = 0.134). Even though a positive correlation between depression and anxiety exists, clinical parameters like age, cancer activity, KPS, and IL-6 do influence depression and anxiety differently. Unlike clinical depression, anxiety is not associated with increased IL-6 levels, however, shows a reciprocal correlation with age.


Assuntos
Ansiedade/psicologia , Neoplasias da Mama/patologia , Neoplasias da Mama/psicologia , Depressão/psicologia , Interleucina-6/sangue , Avaliação de Estado de Karnofsky , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Ansiedade/sangue , Neoplasias da Mama/sangue , Neoplasias da Mama/complicações , Estudos Transversais , Depressão/sangue , Feminino , Humanos , Pessoa de Meia-Idade , Análise de Regressão
5.
Br J Cancer ; 106(2): 274-8, 2012 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-22215062

RESUMO

BACKGROUND: Clinical trials under-represent patients (pts) >65 years. Non-interventional studies (NISs) help to evaluate therapies in daily practice. This NIS evaluates efficacy and safety of cetuximab in combination with chemotherapy in metastatic colorectal cancer (mCRC) pts aged >65 years vs ≤ 65 years. METHODS: A total of 657 pts were recruited into the NIS and analysed applying descriptive statistics and χ(2) or Fisher's exact test. RESULTS: A total of 309 and 305 pts aged ≤ 65 and >65 years, respectively, were documented; 80% showing a reduced ECOG status of 1-2 and 95% having received at least one palliative treatment. Cetuximab was combined with irinotecan according to approval status. Grade III/IV toxicities occurred in 20% of pts without any difference between age groups although the older pts had significantly more pre-existing comorbidities (P=0.001). A total of 64.2% of the pts developed skin rash, which was strongly related to response (P<0.0002) without any difference between age groups (P=0.34). The objective response rates were 37.9% for ages 18-65 years vs 35.4% for >65 years. Progression-free survival (PFS) did not differ between pts 18-65 years old (6.5 months) in comparison with pts >65 years (7.0 months). In a multivariate analysis only ECOG status had a negative impact on PFS (HR: 0,675; 95% Cl, 0.53-0.87; P=0.0019). CONCLUSION: This NIS reports one of the largest mCRC collectives >65 years and reduced performance status. Cetuximab has a similar efficacy and safety profile for pts aged ≤ 65 and >65 years.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Metástase Neoplásica , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados , Cetuximab , Neoplasias Colorretais/complicações , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
6.
Eur J Cancer ; 48(1): 1-11, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21741830

RESUMO

AIM OF THE STUDY: Clinical practice guidelines (CPG) are an appropriate method to optimise routine clinical care. Numerous CPGs for the diagnosis and treatment of breast cancer have been developed by national health institutions or medical societies. While a comparison of methodological criteria has been undertaken before, it is unknown whether these CPGs differ in their actual treatment recommendations. METHODS: We included national breast cancer CPGs from the USA, Canada, Australia, the UK, and Germany that satisfy internationally recognised methodological criteria and are in widespread use in daily clinical care. Treatment recommendations for adjuvant invasive breast cancer including surgery, radiation, endocrine therapy, chemotherapy and anti-HER2-therapy were compared. RESULTS: Recommendations for endocrine therapy show discordances regarding optimal usage of ovarian function suppression for premenopausal patients and aromatase inhibitors for postmenopausal patients. However, most other treatment recommendations exhibit a large degree of congruency. This reflects the fact that they rest on the same evidence base, and that many national guidelines are adopted from other guidelines so that well accepted guidelines are cited within other guidelines. CONCLUDING STATEMENT: Considering that the development of guidelines is a very expensive and resource-intensive task the question arises whether the development of national guidelines in numerous countries is worth the effort since the recommendations differ only marginally.


Assuntos
Neoplasias da Mama/terapia , Carcinoma/terapia , Oncologia/legislação & jurisprudência , Oncologia/métodos , Guias de Prática Clínica como Assunto , Antineoplásicos Hormonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/patologia , Carcinoma/patologia , Governo Federal , Feminino , Humanos , Internacionalidade , Mastectomia/métodos , Mastectomia/estatística & dados numéricos , Gradação de Tumores , Inibidores de Proteínas Quinases/uso terapêutico , Radioterapia/estatística & dados numéricos , Receptor ErbB-2/antagonistas & inibidores , Estados Unidos
7.
Dtsch Med Wochenschr ; 136(10): 486-91, 2011 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-21365526

RESUMO

Breast cancer is the most frequent tumor in women. Clinical research over the last few years has resulted in an increasing differentiation of treatment strategies in the adjuvant setting as well as in metastatic breast cancer. In recent years, the medical treatment of breast cancer was complemented by agents with new mechanisms of action that depend on biological properties of the tumor. As these agents target tumor specific characteristics they are called targeted agents or targeted therapy. Most frequently, different receptors, key proteins of intracellular pathways, thyrosinkinases, or cytokines serve as tumor targets. Even in endocrine treatment relevant changes of practical guidelines emerged. The most important targeted therapies are reviewed with special regard to metastatic breast cancer.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Sistemas de Liberação de Medicamentos/tendências , Medicina de Precisão/métodos , Feminino , Humanos
8.
Breast Cancer Res Treat ; 128(1): 273-81, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21210206

RESUMO

One of the most controversial questions in early breast cancer treatment is the need of chemotherapy in patients with estrogen receptor positive disease. Therefore, we analyzed a group of patients with high estrogen receptor (ER) expression to scrutinize the role of chemotherapy in this situation. To gauge the effect of chemotherapy on recurrence free survival (RFS) three treatment modalities were compared: endocrine treatment only, chemoendocrine treatment, and chemotherapy. 3,971 breast cancer patients whose treatment modalities as well as ER level were known, were included in this retrospective analysis. Their level of ER expression was documented as immunoreactive score (IRS). A high ER group was defined as ER IRS ≥ 9; primary endpoint was RFS. RFS was associated with ER, with the best outcome for strong and the worst result for negative expression. Adjusted to Nottingham prognostic index (NPI), RFS did not differ between the treatment cohorts of endocrine treatment and chemoendocrine treatment (P = 0.828) in the high ER group. Patients with chemotherapy alone fared significantly worse (P = 0.003). Even in high risk patients (according to NPI) the chemoendocrine and the endocrine treatment only groups did not differ significantly (HR = 1.15; 95% CI (0.56-2.34), P = 0.709). Omission of endocrine treatment led to significantly worse outcome (P = 0.013). In conclusion, RFS was significantly longer in patients with high ER expression than with weak or no ER expression. In the high expression group, there was no significant difference in RFS between endocrine treatment only and chemoendocrine therapy-even in high risk patients, for whom chemoendocrine treatment is routinely indicated. It seems insufficient for high ER patients to only consider tumor size, nodal status, and grading in order to decide which patient will benefit from adding chemotherapy to endocrine treatment.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/metabolismo , Detecção Precoce de Câncer , Receptores de Estrogênio/metabolismo , Adulto , Idoso , Antraciclinas/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Cisplatino/uso terapêutico , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Fluoruracila/uso terapêutico , Humanos , Estimativa de Kaplan-Meier , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Taxoides/uso terapêutico , Resultado do Tratamento
9.
Ann Oncol ; 21(3): 633-639, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19880436

RESUMO

BACKGROUND: Sagopilone (ZK-EPO) is a fully synthetic microtubule-stabilizing agent that has demonstrated high antitumor activity in preclinical models. This first-in-human phase I study aimed to determine the maximum tolerated dose (MTD) and dose-limiting toxic effects (DLTs) of 3-weekly sagopilone treatment. PATIENTS AND METHODS: A total of 52 patients with advanced solid tumors received a 30-min infusion of escalating doses of sagopilone (0.6-29.4 mg/m(2)) every 3 weeks. Nine additional patients were recruited to a 3-h infusion arm (16.53- or 22.0-mg/m(2) dose) to assess the incidence of neuropathy with prolonged infusion. RESULTS: The MTD was established as 22.0 mg/m(2). DLTs comprised peripheral sensory neuropathy (PNP), infection, hyponatremia, diarrhea, and central ataxia. PNP was the most common grade 3 event, with a similar incidence in the 30-min and 3-h arms. Hematologic adverse events were rare and of low intensity. One confirmed partial response (PR) and one unconfirmed PR were reported in the 30-min arm, and a further unconfirmed PR was observed in the 3-h arm. Eleven patients achieved disease stabilization. Sagopilone showed high levels of tissue binding and no obvious serum accumulation in both arms. CONCLUSIONS: These data demonstrate that sagopilone therapy is feasible and well tolerated. The recommended dose for phase II studies is 16.53 mg/m(2), once every 3 weeks.


Assuntos
Antineoplásicos/uso terapêutico , Benzotiazóis/uso terapêutico , Epotilonas/uso terapêutico , Neoplasias/tratamento farmacológico , Terapia de Salvação , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/farmacocinética , Benzotiazóis/farmacocinética , Resistencia a Medicamentos Antineoplásicos , Epotilonas/farmacocinética , Estudos de Viabilidade , Feminino , Humanos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias/patologia , Taxa de Sobrevida , Distribuição Tecidual , Resultado do Tratamento
10.
Ann Oncol ; 20(11): 1771-85, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19608616

RESUMO

BACKGROUND: Treatment options for patients with metastatic breast cancer (MBC) include a rapidly expanding repertoire of medical, surgical and supportive care measures. DESIGN: To provide timely and evidence-based recommendations for the diagnostic workup and treatment of patients with MBC, an international expert panel reviewed and discussed the evidence available from clinical trials regarding diagnostic, therapeutic and supportive measures with emphasis on their impact on the quality of life and overall survival of patients with MBC. RESULTS: Evidence-based recommendations for the diagnostic workup, endocrine therapy, chemotherapy, use of targeted therapies and bisphosphonates, surgical treatment and supportive care measures in the management of patients with MBC were formulated. CONCLUSIONS: The present consensus manuscript updates evidence-based recommendations for state-of-the-art treatment of MBC depending on disease-associated and biological variables.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Ensaios Clínicos como Assunto , Medicina Baseada em Evidências , Feminino , Humanos , Mastectomia , Metanálise como Assunto , Prognóstico
11.
Breast Cancer Res Treat ; 117(2): 305-17, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19130218

RESUMO

Therapy decisions in advanced breast cancer (ABC) increasingly require assessment not only of treatment efficacy but also of cost-effectiveness. To this end, we performed a cost-utility analysis by comparing treatment sequences including/omitting fulvestrant in a hypothetical population of hormone receptor-positive (HR+) postmenopausal women with ABC. The analysis was performed from the German health care perspective. Using a first-order sequential Markov model, expected costs and utilities were calculated over a time horizon of 10 years for cohorts of patients with HR+ ABC, previously treated for at least 5 years using adjuvant endocrine therapies. Utilities were primarily quantified in terms of quality adjusted life years (QALY). "Base-case" estimates of state transition rates, resource utilization, and other model parameters were derived from published evidence and expert assessment. The impacts of uncertainties in all key model parameters were evaluated by sensitivity analysis. Costs and benefits were discounted at 3% annually. Including second-line fulvestrant in the treatment sequence led to greater estimated health gains (0.021 QALY) and cost savings of 564 euros ($745, 380 pounds) per patient, i.e. the fulvestrant-containing sequence was "dominant". The prediction of a cost savings was robust with respect to variations in all key parameters. The probability of acceptable cost-effectiveness for the fulvestrant sequence was 72% at a willingness to pay (WTP) of 30,000 euros/QALY ($39,621/QALY, 20,198 pounds/QALY); the probability was even higher at lower WTP and substantially exceeded 50% for any realistic WTP. In a representative population of women with HR+ advanced breast cancer, inclusion of fulvestrant in the treatment sequence provides a cost-effective alternative from the German health care perspective. A high probability of cost-effectiveness is maintained under variations in all key parameters. The results reflect a tendency for patients receiving fulvestrant at an early stage to maintain high quality of life for a longer interval.


Assuntos
Antineoplásicos Hormonais/economia , Neoplasias da Mama/economia , Estradiol/análogos & derivados , Anos de Vida Ajustados por Qualidade de Vida , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Análise Custo-Benefício , Estradiol/economia , Estradiol/uso terapêutico , Feminino , Fulvestranto , Alemanha , Humanos , Cadeias de Markov , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo
12.
Ann Oncol ; 19(6): 1082-9, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18304964

RESUMO

Investigation of high-dose chemotherapy (HD-CT) compared with standard-dose chemotherapy (SD-CT) as adjuvant treatment in patients with primary breast cancer and >/=10 axillary lymph nodes. From November 1993 to September 2000, 307 patients were randomized to receive after four cycles of epirubicin (90 mg/m(2)), cyclophosphamide (600 mg/m(2)) i.v. (every 21 days) and either HD-CT of cyclophosphamide (1500 mg/m(2)), thiotepa (150 mg/m(2)) and mitoxantrone (10 mg/m(2)) i.v. for four consecutive days followed by stem cell transplantation or a SD-CT of three cycles CMF (cyclophosphamide 500 mg/m(2), methotrexate 40 mg/m(2), 5-fluorouracil 600 mg/m(2), i.v. on day 1 and 8, respectively, every 28 days). After a median follow-up of 6.1 years, 166 events with respect to event-free survival (EFS) (SD-CT: 91, HD-CT: 75) have been observed. The hazard ratio of HD-CT versus SD-CT is estimated as 0.80 [95% confidence interval (0.59, 1.08)], P = 0.15. The trend to a superiority of HD-CT as compared with SD-CT with respect to EFS seems to be more pronounced in premenopausal patients as compared with postmenopausal patients and in patients with tumor grade 3 as compared with patients with tumor grade 1/2. With a follow-up of 6 years, there was a trend in favor of HD-CT with respect to EFS not being significant. A proper meta-analysis needs to be undertaken for an evaluation of subgroups of patients who might benefit from HD-CT.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/mortalidade , Neoplasias da Mama/terapia , Transplante de Células-Tronco Hematopoéticas , Linfonodos/patologia , Adulto , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Ciclofosfamida/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Mitoxantrona/administração & dosagem , Estadiamento de Neoplasias , Estudos Prospectivos , Análise de Sobrevida , Tiotepa/administração & dosagem , Transplante Autólogo
13.
Ann Oncol ; 19(5): 871-6, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18209010

RESUMO

BACKGROUND: Proteasome inhibitors are a novel class of compounds entering clinical trials as a method to increase tumour sensitivity to standard chemotherapy. This phase I/II trial was carried out to evaluate the combination of capecitabine and the proteasome inhibitor bortezomib in anthracycline and/or taxane-pretreated patients with metastatic breast cancer. PATIENTS AND METHODS: A total of 35 patients were treated with bortezomib (1.0-1.3 mg/m(2) on days 1, 4, 8 and 11) and capecitabine (1500-2500 mg/m(2) on days 1-14) in 3-week intervals for up to eight cycles. RESULTS: The maximum tolerated doses (MTDs) were bortezomib 1.3 mg/m(2) and capecitabine 2500 mg/m(2). The treatment was generally well tolerated and associated with toxic effects that were consistent with the known side-effects of the individual agents. The intent-to-treat overall response rate was 15% and an additional 27% of patients had stable disease (SD). In the 20 patients treated at the MTD, the response rate was 15% and 40% had SD. Median time to progression and overall survival were 3.5 months [95% confidence interval (CI) 1.9-4.4] and 7.5 months (95% CI 5.6-14.6), respectively. Median duration of response was 4.4 months. CONCLUSION: The combination of bortezomib and capecitabine is well tolerated and has moderate antitumour activity in heavily pretreated patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Carcinoma/secundário , Terapia de Salvação , Antraciclinas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ácidos Borônicos/administração & dosagem , Ácidos Borônicos/efeitos adversos , Bortezomib , Capecitabina , Carcinoma/tratamento farmacológico , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Fluoruracila/análogos & derivados , Doenças Hematológicas/induzido quimicamente , Humanos , Dose Máxima Tolerável , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Pirazinas/administração & dosagem , Pirazinas/efeitos adversos , Análise de Sobrevida , Taxoides/administração & dosagem , Resultado do Tratamento
14.
Anticancer Res ; 28(6B): 3961-4, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-19192656

RESUMO

BACKGROUND: Cisplatin is one of the most active chemotherapeutic agents used in the treatment of advanced squamous cell carcinoma of the head and neck (SCCHN). However, its clinical efficacy is limited by its renal and hematotoxicity profile. In a randomized, multicenter phase III trial, we replaced conventional cisplatin by a liposomal formulation of cisplatin (lipoplatin) and compared the safety and efficacy profiles of patients in the two treatment arms. PATIENTS AND METHODS: Main inclusion criteria were: histologically confirmed SCCHN, age between 18-75 years with sufficient renal function. Main endpoints for this interims analysis were hemato- and nephrotoxicity. First response data were collected. RESULTS: Forty-six patients were evaluable for outcome and toxicity. Grade III and IV hematotoxicity were more frequent in the cisplatin arm (31.7% vs. 12%), with grade IV leucopenia occurring in 22.2%. However, 16% of the patients in that treatment arm experienced grade III anemia compared to only 9.5% treated with the cisplatin regimen. A total 4% of the patients in the lipoplatin arm developed grade IV neuropathy, whereas in the cisplatin arm, 19% developed grade III neuropathy and none developed grade IV. The renal toxicity profile of both drugs also showed marked differences. In the cisplatin arm, 23.8% of patients suffered grade III toxicity. In contrast, no grade III or IV renal toxicity occurred in patients treated with lipoplatin. The efficacy results showed 38.8% objective partial remission in the cisplatin arm vs. 19% in the lipoplatin arm. However 64% of the patients achieved stable disease while being treated with lipoplatin/5-fluorouracil (5-FU), vs. 50% in the cisplatin/5-FU arm. CONCLUSION: Liposomal cisplatin seems to reduce both the renal and hematological toxicity to a clinically relevant extent as compared to conventional cisplatin. The clinical benefit rate is similar for both regimens.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Cisplatino/uso terapêutico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade
15.
Zentralbl Chir ; 132(5): 396-9, 2007 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-17907081

RESUMO

Due to its low incidence there is only few information on optimal systemic therapy of male breast cancer. There are no prospective randomized trials, neither for early breast cancer nor for advanced stages. Retrospective analyses mostly comprise long-term-data from a small number of patients. In terms of epidemiology, cellular receptors or genetics there exist some significant differences between male and female breast cancer. Therefore, the possibility to extrapolate treatment recommendation for male patients from female breast cancer-trials is limited. Despite a high rate of receptor positivity, hormonal therapy seems to be less efficient in men, possibly due to different biological factors. The current standard in endocrine therapy is tamoxifen. It is not known whether tamoxifen therapy is as effective as orchiectomy, but tamoxifen is favoured because of its low side effects. The use of aromatase inhibitors needs to be considered carefully, since aromatization is blocked, but 5-alpha-reductase increases estrogen-like androstanediole. There might be a benefit from additional therapy with GnRH-analoga respectively 5-alpha-reductase inhibitors, but data is not available yet. Combination of GnRH-analoga and antiandrogens does induce tumor remission, but comparison to other endocrine therapies is still lacking. Currently, the efficiency of fulvestrant, an estrogen receptor destructor, is being examined. Cytostatic therapy seems to be as effective as in female breast cancer patients. Nevertheless, convincing prospective trials for the management of early and advanced male breast cancer need to be performed.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama Masculina/tratamento farmacológico , Tamoxifeno/uso terapêutico , Inibidores de 5-alfa Redutase , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Inibidores da Aromatase/uso terapêutico , Terapia Combinada , Ciclofosfamida/efeitos adversos , Estradiol/análogos & derivados , Estradiol/uso terapêutico , Fluoruracila/efeitos adversos , Fulvestranto , Humanos , Masculino , Metotrexato/efeitos adversos , Orquiectomia , Ensaios Clínicos Controlados Aleatórios como Assunto , Taxa de Sobrevida , Resultado do Tratamento
16.
Anticancer Res ; 27(4A): 1759-68, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17649770

RESUMO

The therapeutic opportunities for an improved management of malignant bone disease are currently extensively studied. The conventional management of symptomatic bone lesions in patients with advanced cancer involves various combinations of local and systemic standard anticancer therapies and the symptomatic treatment of skeletal complications. In recent years, bisphosphonates have demonstrated high efficacy to avoid skeletal complications from metastatic bone lesions and to prevent cancer treatment-induced bone loss. Especially in the treatment of patients with bone metastases, secondary to breast cancer, a widespread use of bisphosphonates has been established. With the development of highly potent new-generation bisphosphonates, such as zoledronate, the therapeutic opportunities for bisphosphonates are going to expand. Several current studies have investigated the benefit of zoledronate therapy for bone metastases from a variety of tumor types, including prostate cancer, lung and renal cell cancer and multiple myeloma. Furthermore, bisphosphonates have been shown to significantly reduce antineoplastic therapy-induced bone loss. According to recently published data, it is suggested that bisphosphonates not only play a role in the inhibition of osteoclast-mediated bone resorption, but also have antitumor effects inhibiting tumor cell proliferation, adhesion and invasion, as well as angiogenesis and induction of apoptosis. Further preclinical and clinical investigations are necessary to elucidate the role of bisphosphonates, and large randomized clinical trials should be conducted to confirm the clinical value of bisphosphonates for the prevention of relapse, as well as for the maintainance of net bone density, e.g. during aromatase inhibitor therapy.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Difosfonatos/uso terapêutico , Antineoplásicos/efeitos adversos , Ensaios Clínicos como Assunto , Humanos , Osteoporose/tratamento farmacológico , Osteoporose/etiologia
17.
Anticancer Res ; 27(4A): 1853-62, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17649784

RESUMO

BACKGROUND: The efficacy control for the treatment of bone metastases in breast cancer is difficult and usually initiated later and with longer time between treatment cycles than the restaging of visceral or soft tissue metastases. The amino-terminal propeptide (PINP) of type I collagen as a biochemical indicator of bone turnover might facilitate early and valid disease surveillance. The utility of total PINP was investigated in metastatic breast cancer patients, with or without bone metastases (for monitoring of therapy). The results were compared to the established markers, osteocalcin and beta-carboxyterminal telopeptide (CTX) or crosslaps concentration. PATIENTS AND METHODS: Baseline serum samples of 51 patients with metastastic breast cancer under chemotherapy were investigated. In total, 38 patients had been diagnosed with bone metastases while 13 had no evidence of metastastic spread to the bone. All the patients with bone spread received bisphosphonates in addition to systemic chemotherapy and/or antibody therapy or hormonal treatment. Osteocalcin, CTX and PINP levels were measured on an Elecsys 2010 analyzer (electrochemiluminescence immunoassay--ECLIA). The normal cut-off values were: osteocalcin < 41.3 pg/ml, CTX < 1008 pg/ml and PINP < 95 ng/ml. Based on overall treatment outcome, the patients were grouped as responders (CR/PR), with stable disease (SD) or displaying primary progression (PD). RESULTS: The baseline levels of PINP were significantly higher in patients with bone metastases (median: 92.8 ng/ml) than in those without (median: 63.2 ng/ml, p = 0.044). Patients with more than seven bone metastases had significantly higher PINP levels (median: 149.7 ng/ml) than those with fewer than seven (median: 67.6 ng/ml, p = 0.04). Significant differences were also found for osteocalcin and CTX, at p = 0.02 and p = 0.04, respectively, although the median levels remained under the normal cut-off levels. In terms of response assessment of bone spread, the PINP concentrations decreased in responders from 194.3 ng/ml to 100.4 ng/ml (p = 0.23). In patients with SD, PINP remained at the same level of approximately 70 ng/ml (p = 0.16), but increased in patients with PD from 83.4 ng/ml to 176.5 ng/ml (p = 0.14). These trends rather than statistical difference were probably due to the limited patient cohort. No differences were found for the serum concentrations of PINP, CTX and osteocalcin between post- and pre-menopausal women. CONCLUSION: The PINP levels of the osseous metastatic breast cancer patients were elevated at baseline in comparison to those without bone involvement; the levels correlated to the number of bone metastases but were independent of the menopausal status. Thus, the levels of PINP under therapy might correlate with the response to therapy. Osteocalcin and CTX did not show similar sensitivity for the surveillance of bone metastases.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias Ósseas/secundário , Neoplasias da Mama/patologia , Fragmentos de Peptídeos/sangue , Pró-Colágeno/sangue , Adulto , Idoso , Neoplasias Ósseas/sangue , Remodelação Óssea , Neoplasias da Mama/sangue , Colágeno Tipo I/sangue , Feminino , Humanos , Imunoensaio , Pessoa de Meia-Idade , Osteocalcina/sangue , Peptídeos/sangue , Sensibilidade e Especificidade
18.
Anticancer Res ; 27(1A): 471-5, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17352269

RESUMO

BACKGROUND: Lipoplatin, a novel liposomal formulation of cisplatin, is composed of cisplatin and liposomes based on dipalmityl phosphatidyl glycerol (DPPG), soy phosphatidyl choline (SPC-3), cholesterol and methoxypolyethylene glycol-distearoyl phosphatidylethanolamine (mPEG2000-DSPE). Liposomal encapsulation of cisplatin is designed to increase safety and tolerability by decreasing, e.g., nephrotoxicity through decreased exposure of organs to cisplatin, while effectively delivering the drug to the tumor. In an ongoing phase III trial comparing cisplatin to lipoplatin (both in combination with infusional high-dose 5-Fluoruracil) in advanced head and neck cancer (HNC), a sub-study to determine the pharmacokinetic profile of lipoplatin in comparison to conventional cisplatin was undertaken. MATERIALS AND METHODS: In total, twelve patients with advanced HNC received a combination chemotherapy with either lipoplatin/5-FU or cisplatin/5-FU. Plasma samples were analyzed for concentration of total platinum in patients from both arms. RESULTS: All twelve patients from the pharmacokinetic sub-study were male Caucasians at a mean age of 60 years. There was no difference in age or kidney function between the two treatment groups. The total body clearance for cisplatin was 1.25 L/(hxm2) for the liposomal formulation, compared to 0.62 L/(hxm2) for conventional cisplatin. The terminal half life was half as long for lipoplatin (10.98 h) as compared to cisplatin (24.5h). Even though the maximum observed concentration in the plasma (C(max) was greater for lipoplatin than for cisplatin, the area under the concentration time-curve (AUC) was less (6.5 microg/ml vs. 4.07 microg/ml and 66.85 microg/h/ml vs. 130.33 microg/h/ml, respectively). CONCLUSION: The pharmacokinetic profile of lipoplatin (in combination with 5-FU) suggests that the liposomal formulation results in a greater body clearance and shorter half life than conventional cisplatin, which confirms the clinical observation of decreased taxicity, especially renal deterioration.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Carcinoma de Células Escamosas/metabolismo , Cisplatino/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/sangue , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/tratamento farmacológico , Cisplatino/administração & dosagem , Cisplatino/sangue , Fluoruracila/administração & dosagem , Neoplasias de Cabeça e Pescoço/sangue , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/metabolismo , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade
19.
Ann Oncol ; 18(2): 215-25, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16831851

RESUMO

The present consensus manuscript defines evidence-based recommendations for state-of-the-art treatment of metastatic breast cancer depending on disease-associated and biologic variables.


Assuntos
Neoplasias da Mama/terapia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/metabolismo , Humanos
20.
Internist (Berl) ; 47(12): 1223-4, 1226-8, 2006 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-17063333

RESUMO

Breast cancer, as one of the most frequent tumor entities, is the object of intensive research activity. Clinical research over the last few years has resulted in an increasing differentiation in treatment strategies in the adjuvant setting as well as in metastatic breast cancer. Treatment decision is guided by different risk groups, and relevant changes in clinical practice have arisen in hormonal treatment as well as in chemotherapy. Furthermore, new agents have shown clinical activity, in particular trastuzumab has emerged as standard treatment in HER2 positive breast cancer. It was even licensed in 2006 for adjuvant treatment.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Adulto , Fatores Etários , Idoso , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Antineoplásicos Hormonais/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/mortalidade , Quimioterapia Adjuvante , Ensaios Clínicos como Assunto , Terapia Combinada , Feminino , Humanos , Pessoa de Meia-Idade , Taxa de Sobrevida , Trastuzumab , Resultado do Tratamento
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