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BACKGROUND: We evaluated the feasibility of completing 6 cycles of nab-paclitaxel (nab-P) and carboplatin (C) in a single arm prospective clinical trial for advanced/recurrent EC and safety and efficacy of day (D) 1, 8 nab-P in combination with D1 C q3weeks. METHODS: Patients with early-stage, high-risk, advanced primary/recurrent EC without prior platinum/taxane exposure were enrolled in an open-label, single-institution trial (NCT02744898). Patients received 6 cycles of D1 nab-P 100 mg/m2 IV with C AUC 6 IV and D8 nab-P 100 mg/m2 IV q21D. The trial tested the null hypothesis that subjects completing 6 cycles was ≤0.50 versus the alternative that the proportion is ≥0.75 in a single stage design with alpha = 0.05 and power = 80% with 23 subjects. Patients who completed 6 cycles (primary outcome), objective response rate (ORR) and clinical benefit rate (CBR) were estimated with exact 95% Clopper-Pearson confidence intervals. Progression free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier methods. RESULTS: From 08/2016-03/2018, 23 patients were enrolled. Nineteen patients (82.6%, 95% CI: 61.2%, 95.0%) completed 6 cycles, thus we could reject our null. Twelve patients (52.2%) experienced ≥1 grade 3/4 treatment-related adverse events including: anemia, 6 (26.1%); neutropenia, 5 (21.7%); diarrhea, 3 (13.0%). Fourteen patients (60.1%) reported grade 1 neuropathy. Of 9 patients with measurable target lesions, the ORR was 33.3% (95% CI: 7.5%, 70.1%) and CBR was 55.6% (95% CI: 21.2%, 86.3%). Median PFS in the advanced/recurrent patients was 23.2 (95% CI: 12.1, NR) months. CONCLUSIONS: The nab-P/C D1, 8 regimen met pre-specified feasibility criteria with acceptable toxicity and efficacy. Use of nab-P decreases need for steroid pre-medications, and this carboplatin doublet may prove advantageous for trials assessing combinations with immune checkpoint inhibitors in advanced EC.
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PURPOSE: Advanced non-small cell lung cancer (NSCLC) is a common and lethal malignancy that has rarely benefited from chemotherapy. Erlotinib is highly effective in NSCLC patients selected by clinical characteristics and/or the presence of epidermal growth factor receptor-sensitizing mutations. However, the way to delay or bypass erlotinib resistance is not systematically addressed. Different erlotinib-failure modes have been reported in NSCLC, and strategies to prolong erlotinib efficacy are perhaps adaptable to them. We report the feasibility and efficacy of continued erlotinib maintenance and local salvage radiation to overcome erlotinib resistances in selected NSCLC patients. PATIENTS AND METHODS: Thirty of 52 consecutive erlotinib-treated advanced NSCLC from the NYU Langone Medical Center and the Arnau de Vilanova Hospital of Lleida responded initially to erlotinib. Twenty-six patients eventually showed a generalized-progression to erlotinib, and four progressed in solitary tumor sites. These four patients were treated with continued erlotinib maintenance and local salvage radiation. RESULTS: The progression-free survival (PFS) was statistically similar in patients with oligo or generalized-progression to erlotinib. However, all four cases with solitary-progression did benefit from continued erlotinib maintenance and salvage radiation with 41-140 % prolongation of PFS. It was reflected in an improved overall survival when they were compared with patients with generalized-progression (76.4 vs. 19.9 months; p = 0.018). CONCLUSION: Continued erlotinib maintenance and local salvage radiation is feasible and could contribute to a better outcome in selected NSCLC patients with solitary-progression to erlotinib. Prospective randomized trials of this strategy are warranted (AU)
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Humanos , Masculino , Feminino , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Sobrevivência/psicologiaRESUMO
BACKGROUND: Epithelial ovarian cancer (EOC) patients with BRCA mutations have better prognosis than nonhereditary cases matched for histology and stage and age at diagnosis, especially Ashkenazi Jews (AJ). MATERIALS AND METHODS: We retrospectively reviewed data on 700 highly ethnically heterogeneous patients diagnosed with stage Ic-IV EOC and evaluated for BRCA status between 1995 and 2009 in American, Israeli, and Italian medical centers. RESULTS: The ethnicities of the 190 patients (median age 55.5 years, range 31-83 years) were AJ, Jewish non-Ashkenazi, Caucasian, African-American, Hispanic, or unknown. Ninety were BRCA1/2 carriers (71 BRCA1 and 19BRCA2). The most common mutations in AJ and non-AJ origins were 185delAG and 6174delT. Non-Jewish Caucasians exhibited the widest variation (>20 mutation subtypes). BRCA carriers had significantly prolonged median overall survival (93.6 months) compared with noncarriers (66.6 months; 95% confidence interval 44.5-91.7, P = 0.0081). There was no difference in progression-free survival. CONCLUSIONS: Our data demonstrate a wide variety of BRCA mutations in a highly ethnically diverse EOC population, and confirm that EOC BRCA mutation carriers have better prognosis with longer median survival than patients with nonhereditary disease. The contribution of unclassified BRCA variants to cancer etiology remains undetermined.
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Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Epiteliais e Glandulares/terapia , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapia , Adulto , Negro ou Afro-Americano/genética , Idoso , Idoso de 80 Anos ou mais , Carcinoma Epitelial do Ovário , Intervalo Livre de Doença , Etnicidade/genética , Feminino , Hispânico ou Latino/genética , Humanos , Judeus/genética , Pessoa de Meia-Idade , Mutação , Neoplasias Epiteliais e Glandulares/genética , Neoplasias Ovarianas/genética , Prognóstico , Resultado do Tratamento , População Branca/genéticaRESUMO
PURPOSE: The potential synergy of modulating platinum-induced DNA damage by combining the proteasome inhibitor bortezomib with oxaliplatin was studied in patients with solid tumors, with special attention to avoidance of cumulative neurotoxicity (NT). PATIENTS AND METHODS: In a 3 + 3 dose escalation design, patients received bortezomib at 1.0-1.5 mg/m² on days 1 and 4 and oxaliplatin at 60-85 mg/m² on day 1 of a 14-day cycle. NT assessments were performed at the start of every two cycles. Oxaliplatin pharmacokinetics (PK) were determined pre- and post-bortezomib. RESULTS: Thirty patients were enrolled with 25 (11 men, 14 women) fully evaluable for NT assessments at cycle 2. The median age was 56 years (range 35-74 years); median number of cycles received 2 (range 1-10). At dose levels 2-5 (B 1.3 mg/m²), patients manifested NT grades 3 and 4 at a median 3.4 cycles (range 2-9 cycles): 3 had ataxia (one also with sensory neuropathy or neurogenic hypotension, respectively) and 3 had just sensory neuropathy. A 6th dose-level reducing bortezomib to 1.0 mg/m² with oxaliplatin 85 mg/m²) was explored and no NT or dose limiting toxicities were noted among 7 evaluable patients (5 receiving two or more cycles). Four patients experienced a partial response--one with platinum-resistant ovarian cancer, another with gastroesophageal cancer, another with ampulla of Vater carcinoma, and a patient with cholangiocarcinoma. PK studies at dose levels 1 and 2 showed greater mean ultrafiltrable platinum when oxaliplatin was dosed after bortezomib. CONCLUSIONS: Bortezomib 1.0 mg/m² × 2 every 14 days combines safely with oxaliplatin. At higher doses, cumulative NT (i.e., cerebellar signs and sensory neuropathy) occurs at an accelerated pace perhaps from a PK interaction.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ácidos Borônicos/uso terapêutico , Neoplasias/tratamento farmacológico , Síndromes Neurotóxicas/prevenção & controle , Compostos Organoplatínicos/uso terapêutico , Inibidores de Proteassoma/uso terapêutico , Pirazinas/uso terapêutico , Adulto , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/metabolismo , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Ácidos Borônicos/administração & dosagem , Ácidos Borônicos/efeitos adversos , Bortezomib , Estudos de Coortes , Relação Dose-Resposta a Droga , Monitoramento de Medicamentos , Feminino , Neoplasias Gastrointestinais/sangue , Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Gastrointestinais/metabolismo , Neoplasias Gastrointestinais/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/sangue , Neoplasias/metabolismo , Neoplasias/patologia , Síndromes Neurotóxicas/fisiopatologia , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Compostos Organoplatínicos/farmacocinética , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Oxaliplatina , Inibidores de Proteassoma/administração & dosagem , Inibidores de Proteassoma/efeitos adversos , Pirazinas/administração & dosagem , Pirazinas/efeitos adversos , Índice de Gravidade de Doença , Carga Tumoral/efeitos dos fármacosRESUMO
PURPOSE: Advanced non-small cell lung cancer (NSCLC) is a common and lethal malignancy that has rarely benefited from chemotherapy. Erlotinib is highly effective in NSCLC patients selected by clinical characteristics and/or the presence of epidermal growth factor receptor-sensitizing mutations. However, the way to delay or bypass erlotinib resistance is not systematically addressed. Different erlotinib-failure modes have been reported in NSCLC, and strategies to prolong erlotinib efficacy are perhaps adaptable to them. We report the feasibility and efficacy of continued erlotinib maintenance and local salvage radiation to overcome erlotinib resistances in selected NSCLC patients. PATIENTS AND METHODS: Thirty of 52 consecutive erlotinib-treated advanced NSCLC from the NYU Langone Medical Center and the Arnau de Vilanova Hospital of Lleida responded initially to erlotinib. Twenty-six patients eventually showed a generalized-progression to erlotinib, and four progressed in solitary tumor sites. These four patients were treated with continued erlotinib maintenance and local salvage radiation. RESULTS: The progression-free survival (PFS) was statistically similar in patients with oligo or generalized-progression to erlotinib. However, all four cases with solitary-progression did benefit from continued erlotinib maintenance and salvage radiation with 41-140 % prolongation of PFS. It was reflected in an improved overall survival when they were compared with patients with generalized-progression (76.4 vs. 19.9 months; p = 0.018). CONCLUSION: Continued erlotinib maintenance and local salvage radiation is feasible and could contribute to a better outcome in selected NSCLC patients with solitary-progression to erlotinib. Prospective randomized trials of this strategy are warranted.
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Adenocarcinoma Bronquioloalveolar/terapia , Adenocarcinoma/terapia , Carcinoma Pulmonar de Células não Pequenas/terapia , Quimiorradioterapia , Neoplasias Pulmonares/terapia , Inibidores de Proteínas Quinases/uso terapêutico , Quinazolinas/uso terapêutico , Adenocarcinoma/mortalidade , Adenocarcinoma/secundário , Adenocarcinoma Bronquioloalveolar/mortalidade , Adenocarcinoma Bronquioloalveolar/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/secundário , Progressão da Doença , Cloridrato de Erlotinib , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Dosagem Radioterapêutica , Estudos Retrospectivos , Terapia de Salvação , Taxa de SobrevidaRESUMO
BACKGROUND: Hypercalcemia has been reported in association with a number of malignancies, but it is an unusual manifestation of ovarian cancer. This finding at presentation (possibly aggravated by oral calcium intake) led to discovery of a clear cell carcinoma of the ovary. The implications and pathophysiology of this association are reviewed. CASE REPORT: Following presentation with abdominal symptoms, this premenopausal woman was found to have bilateral adnexal masses and hypercalcemia. Her parathormone-related polypeptide was found to be elevated. After surgery and staging, she received adjuvant carboplatin and paclitaxel (later substituted by docetaxel). She has done well on her long-term follow-up. CONCLUSIONS: This rare paraneoplastic manifestation of ovarian cancer may be associated with long-term survival if discovered at an early stage. In this instance, further benefit may have been obtained from adjuvant platinum-based chemotherapy.
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BACKGROUND: Suppression of neoangiogenesis and pegylated liposomal doxorubicin (PLD) each contribute to the management of platinum-resistant/refractory ovarian cancer. The aim of this study is to test the combination of bevacizumab and PLD in women with resistant or refractory ovarian cancer. METHODS: Eligibility criteria were no more than two prior treatments with platinum-containing regimens and one additional regimen, without anthracyclines. Treatment was administered every 3 weeks (bevacizumab 15 mg/kg beginning on cycle 2 and PLD 30 mg/m(2)). The primary end point was progression-free survival (PFS) at 6 months; the secondary end points included side-effects, overall response rates (ORR) and survival (OS). RESULTS: Forty-six patients were enrolled. The average number of courses administered was 7. The median PFS was 6.6 months (range 1-24.6 months) according to Gynecologic Cancer Intergroup Committee (GCIC) criteria and 7.8 months (range 2-13.3 months) according to Response Evaluation Criteria in Solid Tumors (RECIST). The median OS was 33.2 months (range 3-37.5+ months). The ORR was 30.2% [95% confidence interval (CI) 17.2-46.1] and the clinical benefit rate (CBR) was 86.1% (95% CI 72.1-94.7). Adverse events included mucosal and dermal erosions (30% grade 3) and asymptomatic cardiac dysfunction. Additional toxic effects included hypertension, headache, renal dysfunction and proteinuria, wound healing delay, and one episode each of central nervous system (CNS) ischemia and hemolytic uremic syndrome. CONCLUSION: PLD with bevacizumab has improved activity in recurrent ovarian cancer with increased toxicity.
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Anticorpos Monoclonais Humanizados/uso terapêutico , Doxorrubicina/uso terapêutico , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Epiteliais e Glandulares/mortalidade , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/efeitos adversos , Inibidores da Angiogênese/uso terapêutico , Antibióticos Antineoplásicos/efeitos adversos , Antibióticos Antineoplásicos/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab , Hidrocarbonetos Aromáticos com Pontes/farmacologia , Carcinoma Epitelial do Ovário , Intervalo Livre de Doença , Doxorrubicina/efeitos adversos , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Platina/farmacologia , Taxoides/farmacologia , Resultado do TratamentoRESUMO
Genes implicated in the devastating occurrences of cancers mostly arising in the breast and ovaries within certain 'high-risk' families were mapped and then cloned not even two decades ago. Some clairvoyant students of the subject anticipated that this 'assignation of risk' would herald a new era in the prevention, treatment and insights into pathogenesis of neoplasia. However, few would have predicted the accelerated pace of knowledge that ensued. The successive symposia that we held on this subject have given us a unique perspective on the extent of this progress. This supplement and the selected papers that have been assembled document accomplishments in genetics, epidemiology, early detection, treatment, preventive measures, as well as in the ethical and psychosocial consequences enveloping families at risk. It also reveals how the convergence of the laboratory, the clinic and the public across two continents is able to ignite discovery and its applications.
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Neoplasias da Mama/genética , Neoplasias da Mama/prevenção & controle , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/prevenção & controle , Feminino , Genes BRCA1 , Genes BRCA2 , Predisposição Genética para Doença , HumanosRESUMO
Advances in the study of BRCA1 and BRCA2 gene functions have relied on the development of animal models for seeking to explore further what we have learned from the human disease. Specifically, mouse models of a 'triple-negative' breast cancer (utilizing conditional knockout of BRCA1 and p53 in the breast), of an endometrioid ovarian cancer (based on oncogenic kras and loss of function of pten), and of anatomic and functional consequences of BRCA1 mutations in granulosa cells, have led to further inquiry into the pathogenesis and therapeutic consequences of genetic alterations. A striking susceptibility of these murine malignancies to platinum drugs has emerged, providing further confidence in their relevance to the human disease. In addition to these models, the pathogenesis of high-grade serous disease derived from risk-reducing surgeries in mutation carriers has pointed to a role of mutations in p53 commonly encountered in tubal intraepithelial carcinomas.
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Neoplasias da Mama/genética , Carcinoma Endometrioide/genética , Modelos Animais de Doenças , Genes BRCA1 , Genes BRCA2 , Neoplasias Mamárias Experimentais/genética , Neoplasias Ovarianas/genética , Animais , Feminino , Genes p53 , Humanos , Camundongos , Camundongos KnockoutRESUMO
Details on the 28-year treatment history of a patient with an endocrine-responsive breast cancer are provided. She was originally diagnosed as having a T1N0M0 cancer after a modified radical mastectomy at age 41. Fifteen years later, in 1998, she presented with hemoptysis and pleuritic chest pain: a 10 cm right atrial tumor and estrogen receptor (ER) positive endobronchial and adjacent lung parenchyma adenocarcinoma were documented. Epithelial markers normalized as she manifested a partial response (PR) lasting 3 years with tamoxifen treatment. From 2001 to 2007 she benefitted from exemestane treatment. Upon progression in the previous lung area and left adrenal, exemestane withdrawal led to transient decrease in markers. Six months later (in July 2008), with growth in her adrenal tumor, laparoscopic adrenalectomy was performed: in addition to ER positivity, the tumor showed Her2 overexpression and amplification. She has subsequently had some control of disease with fulvestrant, letrozole + trastuzumab, and subsequently letrozole + lapatinib. In addition to the chronicity of disease, this history illustrates the expanding range of treatments available for endocrine-responsive breast cancer commensurate to our greater understanding of tumor biology.
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BACKGROUND: Cisplatin is a highly effective chemotherapeutic agent against epithelial ovarian cancer but is associated with significant toxicities. SPI-77 is a liposomal pegylated formulation of cisplatin that was developed to reduce systemic toxicity and to better deliver cisplatin to tumors. We assessed the response rates and safety of SPI-77, in patients with recurrent epithelial ovarian cancer. PATIENTS AND METHODS: Patients were selected for having previously achieved a platinum treatment free interval of greater than 6 months (e.g. platinum-sensitive) and high potential of achieving responses when rechallenged with a platinum drug. SPI-77 was administered at a dose of 260 mg/m(2) every 21 days until disease progression. RESULTS: Enrollment was terminated after 5 patients were treated because of concern with the adequacy of the formulation. Four out of the five patients had stable disease as best response. While no serious, unexpected adverse events occurred in spite of large cumulative doses of SPI-77, there were concerns related to the large lipid load and prolonged persistence of residual platinum in body stores. CONCLUSION: The results of this study, although inconclusive regarding its primary endpoints, provide some important lessons for the development of similar liposomal platinum agents.
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Adenocarcinoma Papilar/tratamento farmacológico , Adenocarcinoma/tratamento farmacológico , Cisplatino/uso terapêutico , Cistadenocarcinoma Seroso/tratamento farmacológico , Neoplasias do Endométrio/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Adenocarcinoma/secundário , Adenocarcinoma Papilar/secundário , Adulto , Cistadenocarcinoma Seroso/secundário , Neoplasias do Endométrio/secundário , Feminino , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia/patologia , Neoplasias Ovarianas/patologia , PrognósticoRESUMO
This clinical vignette illustrates how our therapeutic approaches to early stages of multiple myeloma have changed over the past decade with novel therapies reducing disease and preventing disease progression. Recent paradigms of multiple myeloma describe the disease as a spectrum of clinical stages, including asymptomatic 'smoldering' states that progress to symptomatic states. The average 5-year survival rate of patients with multiple myeloma diagnosed between 1996 and 2004 according to surveillance epidemiology and end results (SEER) data is 35.9%. Here, we describe the use of novel therapeutic agents including bortezomib, lenalidomide, bisphosphonates, Doxil/Caelyx, and dexamethasone, and their success in affecting the course of disease. Multiple trials have shown an increased benefit of these newer agents over prior multiple myeloma treatment regimens. At 13 years and 8 months from diagnosis, our patient is doing well, and thus is a model of how long-term control of multiple myeloma prolongs survival.
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Antineoplásicos/farmacologia , Proteína BRCA1/deficiência , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos , Neoplasias Experimentais/tratamento farmacológico , Animais , Proteína BRCA1/genética , Resistencia a Medicamentos Antineoplásicos/genética , Camundongos , Camundongos Knockout , Neoplasias Experimentais/genética , Neoplasias Experimentais/patologiaRESUMO
To date, the presence of a hereditary background has not influenced the selection of drug treatment in breast cancer. However, increasingly, negative hormone receptors and Her2 (often referred to as 'triple negative') or a medullary carcinoma histology has been reported in BRCA mutation carriers. Accordingly, such patients are often considered for adjuvant protocols based on chemotherapy (and not based on endocrine manipulations or trastuzumab). Mouse models introducing a conditional BRCA-null expression in the breast have recently provided powerful support for cisplatin-based treatment and have implications for the design of adjuvant studies in these patients.
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Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Modelos Animais de Doenças , Desenho de Fármacos , Genes BRCA1 , Genes BRCA2 , Animais , Neoplasias da Mama/genética , Resistencia a Medicamentos Antineoplásicos , HumanosRESUMO
INTRODUCTION: We describe a screening and prevention programme primarily targeting under-served minority women at high risk of breast and/or ovarian cancer. Women attending this Bellevue Hospital Center (BHC) Clinic were either self-referred from a variety of special outreach programmes or referred internally by medical professionals caring for relatives or friends. Our objective was to delineate referral sources and preliminary risk-assessment findings in relation to demographic features in this population. METHODS: Following a detailed family and personal history intake and physical examination, each woman on her initial visit is categorized into a low (standard) risk, high-risk or indeterminate-risk group. Women found to be at high risk of developing breast and/or ovarian cancers are referred for further testing, additional screening measures, or participation in chemoprevention trials. All other women are counselled concerning follow-up and lifestyle issues. RESULT: Between 2003 and 2007, 171 women for whom complete information was obtained were analysed. Thirty-four of the women were Caucasians (19.8%) and 137 (80.2%) were ethnically diverse minority women. Sixty-two (36.2%) were found to be at high risk with a median age of 42 years. The majority of the high-risk women were referred to the clinic by medical professionals (58%), most of whom were from within the BHC health care system. In fact, one-fourth of the referrals were women who carried a diagnosis of cancer, mostly arising in the breast, and who were concerned with risks to other family members. Trends in genetic testing results indicate fewer mutations among high-risk Asians than among other ethnicities. CONCLUSION: Accurate risk assessments and implementation of screening and prevention measures have been challenging during the first few years of operation. Nevertheless, the need for providing consultation from internal referrals and the potential for genetic and psychosocial research in an ethnically diverse population are powerful incentives for continuing to evolve these services.
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Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/secundário , Coriocarcinoma/diagnóstico por imagem , Coriocarcinoma/secundário , Neoplasias Uterinas/patologia , Adulto , Neoplasias Encefálicas/terapia , Coriocarcinoma/terapia , Evolução Fatal , Feminino , Humanos , Gravidez , Tomografia Computadorizada por Raios X , Neoplasias Uterinas/diagnóstico por imagem , Neoplasias Uterinas/terapiaRESUMO
BACKGROUND: We have previously established the recommended phase II dose (RPTD) of ixabepilone as 40 mg/m(2) administered over 1 h repeated every 3 weeks with neuropathy as a cumulative dose-limiting toxicity. We expanded the cohort at the RPTD to include detailed assessment of nerve damage in these patients. We report our findings on vibration perception threshold (VPT) and neuropathy. PATIENTS AND METHODS: Forty-four patients were treated with a median (range) of three (1-14) cycles of ixabepilone. The VPT (5-min duration) and nerve conduction test (NCT, 10-min duration) were carried out in the office, before ixabepilone dosing, and every two cycles thereafter. RESULTS: Neuropathy (grade 1 and grades 2-3) was observed in 17 (38.6%) and 11 (25%) patients, respectively. The mean increase in VPT as a function of grade 0-1 versus grades 2-3 neuropathy was 0.235 +/- 0.03 versus 0.869 +/- 0.09 (P = 0.049) vibration units. The F-wave frequency and distal motor latency, as assessed using the NCT, did not correlate with clinical neurotoxicity. CONCLUSION: The change in VPT is observed early and likely reflects early vibration perception change. Mean change in VPT correlates with the severity of clinical neuropathy. Whether VPT change predicts onset of severe neuropathy warrants prospective testing and validation.
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Antineoplásicos/efeitos adversos , Epotilonas/efeitos adversos , Neoplasias/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Distúrbios Somatossensoriais/induzido quimicamente , Vibração , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Condução Nervosa/efeitos dos fármacos , Exame Neurológico/métodosRESUMO
The co-existence of breast and ovarian cancers in the same individual should raise suspicion of a hereditary process. Patients with either BRCA1 or BRCA2 germ-line mutations have an average risk of 39% and 11% respectively of developing ovarian cancer by the age of 70; they have a risk of 35-85% of developing breast cancer in their lifetime. We report here unusual pathologic features in a BRCA2 germ-line mutation carrier recently diagnosed with synchronous breast and ovarian cancers, and summarize the findings in six other women who were diagnosed with ovarian cancer either simultaneously with the diagnosis of breast cancer or at varying times after the diagnosis. While in most instances this may be a coincidental occurrence in highly susceptible individuals, the patient we highlight raises the provocative hypothesis that at times breast cancer metastasizes to the ovaries of mutation carriers and stimulates the development of an ovarian cancer as well as other cancers. In addition, these ovarian cancers may have different mechanisms of metastases predisposing them to travel to unusual sites.