RESUMO
Patients with indolent non-Hodgkin lymphoma (NHL) have multiple treatment options yet there is no consensus as to the best initial therapy. Lenalidomide, an immunomodulatory agent, has single agent activity in relapsed lymphoma. This trial was conducted to assess feasibility, efficacy, and safety of adding lenalidomide to rituximab, cyclophosphamide, and dexamethasone (LR-CD) in untreated indolent NHL patients requiring therapy. This was a single institution phase II trial. Treatment consisted of IV rituximab 375 mg/m2 day 1; oral lenalidomide 20 mg days 1-21; cyclophosphamide 250 mg/m2 days 1, 8, and 15; and dexamethasone 40 mg days 1, 8, 15, and 22 of a 28-day cycle. Treatment continued 2 cycles beyond best response for a maximum of 12 cycles without rituximab maintenance. Thirty-three patients were treated. Median age was 68 (43-83 years). 39% had stage IV disease. Histologic subtypes included 8 follicular lymphoma (FL), 7 marginal zone lymphoma (MZL) (1 splenic, 2 extranodal, and 4 nodal), 15 Waldenström's macroglobulinemia (WM), 1 lymphoplasmacytic lymphoma, 1 small lymphocytic lymphoma, and 1 low-grade B-cell lymphoma with plasmacytic differentiation (unable to be classified better as MZL or LPL). Hematologic toxicity was the most common adverse event. Median time of follow-up was 23.4 months (range 1.8-50.9). The overall response rate was 87.9%, with 30.3% complete response. The median duration of response was 38.7 months. The median progression free survival was 39.7 months, while median overall survival (OS) has not yet been reached. Lenalidomide can be safely added to a simple regimen of rituximab, oral cyclophosphamide, and dexamethasone and is an effective combination as initial therapy for low-grade B-cell NHL.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma não Hodgkin/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/administração & dosagem , Dexametasona/administração & dosagem , Intervalo Livre de Doença , Feminino , Humanos , Lenalidomida , Linfoma de Células B/tratamento farmacológico , Linfoma não Hodgkin/patologia , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Rituximab/administração & dosagem , Análise de Sobrevida , Talidomida/administração & dosagem , Talidomida/análogos & derivados , Resultado do TratamentoAssuntos
Complicações Hematológicas na Gravidez/epidemiologia , Mielofibrose Primária/epidemiologia , Aborto Habitual/epidemiologia , Aborto Habitual/etiologia , Adulto , Anticoagulantes/uso terapêutico , Aspirina/uso terapêutico , Diabetes Gestacional/epidemiologia , Feminino , Morte Fetal/etiologia , Hemorragia/epidemiologia , Hemorragia/etiologia , Humanos , Mutação , Trabalho de Parto Prematuro/epidemiologia , Hemorragia Pós-Parto/epidemiologia , Hemorragia Pós-Parto/etiologia , Pré-Eclâmpsia/epidemiologia , Gravidez , Complicações Hematológicas na Gravidez/tratamento farmacológico , Complicações Hematológicas na Gravidez/genética , Resultado da Gravidez , Mielofibrose Primária/tratamento farmacológico , Mielofibrose Primária/genética , Trombose/epidemiologia , Trombose/etiologiaRESUMO
Everolimus is an oral raptor mTOR inhibitor and has shown activity in patients with Waldenstrom's macroglobulinemia (WM). This study examines a large cohort of patients with relapsed/refractory WM with long-term follow up for survival. Patients were eligible if they had measurable disease, a platelet count >75,000 x 10(6)/L, an absolute neutrophil count >1,000 x 10(6)/L. Patients received everolimus 10 mg PO daily and were evaluated monthly. A success was defined as a complete or partial response (PR); minor responses (MR) were recorded and considered to be of clinical benefit. Sixty patients were enrolled and treated. The overall response rate (ORR) was 50% (all PR); the clinical benefit rate including MR or better was 73% (95% CI: 60-84%) with 23% MR. The median time to response for patients who achieved PR was 2 months (range, 1-26). The median duration of response has not been reached and median progression-free survival (PFS) was 21 months. Grade 3 or higher toxicities (at least possibly related to everolimus) were observed in 67% of patients. The most common grade 3 or 4 toxicities were anemia (27%), leukopenia (22%), and thrombocytopenia (20%). Other nonhematological toxicities were diarrhea (5%), fatigue (8%), stomatitis (8%) and pulmonary toxicity (5%). Everolimus has a high single-agent activity of 73% including MR, with a progression free survival of 21 months, indicating that this agent is active in relapsed/refractory WM.
Assuntos
Sirolimo/análogos & derivados , Serina-Treonina Quinases TOR/antagonistas & inibidores , Macroglobulinemia de Waldenstrom/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Alquilantes/uso terapêutico , Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais Murinos/uso terapêutico , Antimetabólitos/uso terapêutico , Medula Óssea/patologia , Diarreia/induzido quimicamente , Intervalo Livre de Doença , Resistência a Medicamentos , Everolimo , Fadiga/induzido quimicamente , Feminino , Doenças Hematológicas/induzido quimicamente , Humanos , Imunoglobulina M/sangue , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Dor/induzido quimicamente , Paraproteínas/análise , Recidiva , Rituximab , Sirolimo/efeitos adversos , Sirolimo/farmacologia , Sirolimo/uso terapêutico , Estomatite/induzido quimicamente , Resultado do Tratamento , Macroglobulinemia de Waldenstrom/sangueRESUMO
BACKGROUND: The use of telemedicine (TELE) increased exponentially during the COVID-19 pandemic. While patient experience with TELE has been studied in other medical disciplines, its impact and applicability to integrative medicine practices remain unknown. OBJECTIVE: The aim of this study is to assess the impact of visit modality, TELE versus face-to-face (F2F) encounters, on patient experience at an integrative medicine practice at a single academic medical center. Given the significant role of the patient-physician relationship, therapeutic presence, and touch in integrative medicine, we hypothesized that TELE would result in reduced patient experience compared to traditional F2F encounters. METHODS: A retrospective examination of Press Ganey surveys at an academic, consultative, and integrative medicine practice was conducted. Anonymous surveys completed by patients, older than 18 years of age, who had TELE or F2F appointments from April 1, 2020, to March 31, 2023, were included. At our medical center, patients commonly travel in from out of state for complex care. We examined percentage "top box" scores (ie, the percentage of respondents who selected the most positive response category on the survey, "very good"), across a variety of experience metrics. ANOVA and chi-square analyses were completed, with a significance threshold of P<.05. RESULTS: Over the 36 months, a total of 1066 surveys were completed and returned (TELE: n=333; F2F: n=733). Overall, 73% (n=778) of respondents were female with an average age of 57.6 (SD 13.84) years. Most patients were English-speaking (n=728, 99.3%), White (n=1059, 92.7%), and not Hispanic or Latino (n=985, 92.4%). There was significantly higher satisfaction with access to care for TELE visits compared to F2F visits. There were no differences in satisfaction with the care provider or in overall experience. When examining the specific aspects of using technology during TELE visits, there were no differences in audio quality, visual quality, or ease of talking to the care provider based on sex. There was, however, a difference in video quality based on age, where those 80 years and older rated significantly lower video quality compared to all other age groups. CONCLUSIONS: Top-level patient experience can be attained with TELE integrative medicine visits. Additional studies, particularly those correlating positive experience findings with specific behaviors used during TELE visits, would further our understanding of the integrative medicine patient experience. In the meantime, efforts should be made to ensure a policy that promotes the ongoing provision of TELE in integrative medicine.
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The Philadelphia negative myeloproliferative neoplasms, including polycythemia vera, essential thrombocythemia, and myelofibrosis, are associated with substantial vascular and transformative complications. Standard therapy for high-risk disease, particularly in patients that have failed initial therapy, remains controversial. Non-pegylated interferon has previously been shown to be effective in controlling erythrocytosis, thrombocytosis and thrombotic complications, but was found to have poor tolerability and excessive adverse effects. Recently, pegylated interferon alpha-2a was introduced and found to be better tolerated and less toxic than standard interferon. In addition, in recent phase II trials, pegylated interferon alpha-2a therapy was found to induce both hematologic and molecular remissions. We retrospectively analyzed 118 myeloproliferative patients who underwent pegylated interferon alpha-2a treatment. Responses were evaluated by ELN, IWG-MET and EUMNET standardized criteria sets and adverse effects were analyzed.
Assuntos
Antineoplásicos/uso terapêutico , Interferon-alfa/uso terapêutico , Transtornos Mieloproliferativos/tratamento farmacológico , Polietilenoglicóis/uso terapêutico , Adolescente , Adulto , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Estudos de Coortes , Feminino , Humanos , Interferon-alfa/administração & dosagem , Interferon-alfa/efeitos adversos , Masculino , Pessoa de Meia-Idade , Transtornos Mieloproliferativos/patologia , Estadiamento de Neoplasias , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/efeitos adversos , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: To evaluate the efficacy and biological effects of the gemcitabine/tanespimycin combination in patients with advanced ovarian and peritoneal cancer. To assess the effect of tanespimycin on tumor cells, levels of the chaperone proteins HSP90 and HSP70 were examined in peripheral blood mononuclear cells (PBMC) and paired tumor biopsy lysates. METHODS: Two-cohort phase II clinical trial. Patients were grouped according to prior gemcitabine therapy. All participants received tanespimycin 154 mg/m(2) on days 1 and 9 of cycle 1 and days 2 and 9 of subsequent cycles. Patients also received gemcitabine 750 mg/m(2) on day 8 of the first treatment cycle and days 1 and 8 of subsequent cycles. RESULTS: The tanespimycin/gemcitabine combination induced a partial response in 1 gemcitabine naïve patient and no partial responses in gemcitabine resistant patients. Stable disease was seen in 6 patients (2 gemcitabine naïve and 4 gemcitabine resistant). The most common toxicities were hematologic (anemia and neutropenia) as well as nausea and vomiting. Immunoblotting demonstrated limited upregulation of HSP70 but little or no change in levels of most client proteins in PBMC and paired tumor samples. CONCLUSIONS: Although well tolerated, the tanespimycin/gemcitabine combination exhibited limited anticancer activity in patients with advanced epithelial ovarian and primary peritoneal carcinoma, perhaps because of failure to significantly downregulate the client proteins at clinically achievable exposures.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Peritoneais/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Benzoquinonas/administração & dosagem , Benzoquinonas/efeitos adversos , Biomarcadores Tumorais/metabolismo , Carcinoma Epitelial do Ovário , Linhagem Celular Tumoral , Estudos de Coortes , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Feminino , Proteínas de Choque Térmico HSP70/metabolismo , Proteínas de Choque Térmico HSP90/metabolismo , Humanos , Lactamas Macrocíclicas/administração & dosagem , Lactamas Macrocíclicas/efeitos adversos , Pessoa de Meia-Idade , Neoplasias Epiteliais e Glandulares/metabolismo , Neoplasias Ovarianas/metabolismo , Neoplasias Peritoneais/metabolismo , Taxa de Sobrevida , GencitabinaRESUMO
Castleman's disease (CD) is a rare, poorly understood lymphoproliferative disease. The spectrum of symptoms and course of disease are broad, but there is no large study describing the natural history of this disease. Basic clinic and laboratory data from the records of 113 patients with CD evaluated at the Mayo Clinic and University of Nebraska were abstracted. The impact of these variables on overall survival (OS) from time of diagnosis was evaluated. Sixty patients had multicentric disease. Of the patients with multicentric CD, 32% had criteria sufficient for a diagnosis of POEMS syndrome. For all patients, 2, 5, and 10-year OS was 92%, 76%, 59%, respectively. Most of the factors identified as risk factors for death on univariate analysis cosegregated with diagnostic criteria for POEMS syndrome, which supported the concept of four categories of CD, which are (along with their 5-year OS): (1) unicentric CD (91%); (2) multicentric CD associated with the osteosclerotic variant of POEMS syndrome (90%); (3); multicentric CD without POEMS syndrome (65%); and (4) multicentric CD with POEMS syndrome without osteosclerotic lesions (27%). We have demonstrated that CD represents a spectrum of disease that can be differentiated by simple prognostic factors that provide a framework for further study.
Assuntos
Hiperplasia do Linfonodo Gigante/diagnóstico , Síndrome POEMS/diagnóstico , Adolescente , Adulto , Idoso , Biópsia por Agulha , Hiperplasia do Linfonodo Gigante/complicações , Hiperplasia do Linfonodo Gigante/mortalidade , Hiperplasia do Linfonodo Gigante/terapia , Criança , Pré-Escolar , Interpretação Estatística de Dados , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Síndrome POEMS/complicações , Síndrome POEMS/mortalidade , Síndrome POEMS/terapia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
We have previously reported the benefits of combination therapy with thalidomide and prednisone for the improvement of cytopenias and splenomegaly for patients with myelofibrosis (MF); both primary and those arising from an antecedent polycythemia vera (PV) and essential thrombocythemia (ET). We report here the overall efficacy of three different thalidomide-prednisone based regimens (alone or in combination with either oral cyclophosphamide for three months or continuous weekly etanercept) when assessed by the IWG-MRT response criteria which were developed after completion of these studies. Additionally we report on the durability of response and long-term follow-up. We observed an overall response rate of 28% by IWG-MRT criteria (mostly clinical improvement - 22% anemia, 8% splenomegaly) with a median duration of response of 8.5 months. Toxicities primarily consisted of neuropathy (Grade 3 or higher neuropathy in 6%) and cytopenias (Grade 3 or higher in 20%). After a median follow-up of three years, fourteen patients (28%) had expired from MF at the time of this analysis with median survival of 36 months.
Assuntos
Prednisona/uso terapêutico , Mielofibrose Primária/tratamento farmacológico , Talidomida/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: We describe a phase II clinical trial of the combination of ribociclib and letrozole for treatment of relapsed oestrogen receptor (ER)-positive ovarian cancer (OC) and endometrial cancer (EC). The primary endpoint was the proportion of patients alive, progression-free survival (PFS), and still on treatment at 12 weeks (PFS12), with 45% or greater considered positive. METHODS: Patients with measurable, relapsed ER-positive OC or EC (platinum-sensitive or resistant) were eligible and treated with 400 mg of oral ribociclib and 2.5 mg of oral letrozole daily. Patient-derived xenografts (PDXs) were created from imaging-guided tumour biopsies. RESULTS: Forty patients (20 OC and 20 EC) were enrolled. A PFS12 of 55% was observed in the EC cohort and 50% in the OC cohort. A PFS greater or equal to 24 weeks (PFS24) was seen in 20% (4/20) of the OC cohort and 35% (7/20) of the EC cohort. The greatest benefit was seen in low-grade serous OC (LGSOC) (3/3, 100% PFS24) and grades 1 and 2 EC (5/11, 45% PFS24). All three LGSOC patients obtained at least a partial response lasting for over 2 years, with two of the three patients still on treatment. PDX tumour engraftment was feasible in 45% of patients. Positive survival effects of the combination of ribociclib and letrozole were observed in two of three EC PDX models. CONCLUSION: Ribociclib and letrozole have promising clinical activity in relapsed ER-positive OC and EC, particularly in LGSOC and relapsed ER-positive grade 1 and 2 EC. Generation of PDX models is feasible with positive survival effects observed in EC models. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov registry (NCT02657928).
Assuntos
Neoplasias do Endométrio , Receptores de Estrogênio , Aminopiridinas , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Intervalo Livre de Doença , Neoplasias do Endométrio/tratamento farmacológico , Feminino , Humanos , Letrozol/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Purinas , Receptores de Estrogênio/uso terapêuticoRESUMO
Hemophagocytic lymphohistiocytosis (HLH) is a rare syndrome of pathologic immune activation in children that is increasingly being recognized in adults. Efficacy data for the HLH-04 protocol in adults is lacking. This study retrospectively analyzed 31 adult patients, median age 46 years, who received HLH-04 from 1/1/2004 to 5/1/2018. HLH etiology included malignancy (n = 9), autoimmune (n = 8), infection (n = 8), and idiopathic (n = 6). Eighteen patients were evaluable for response at week 4 with 7 having no response, 11 reaching partial response, and 0 reaching complete response (CR). Six patients eventually achieved CR at a median 195 days. The 1-year overall survival (OS) was 35% and median OS was 3.2 months. Univariate analysis showed shorter survival for hemoglobin <9 g/dL (HR 4.29, p = 0.003), platelets <100 × 109/L (HR 4.06, p = 0.027), ANC <1 × 109/L (HR 5.24, p = 0.001), and total bilirubin >1.2 mg/dL (HR 3.30, p = 0.022). Outcomes of adults treated with HLH-04 remain dismal and newer treatment modalities are needed.
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Linfo-Histiocitose Hemofagocítica , Neoplasias , Adulto , Criança , Humanos , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Pessoa de Meia-Idade , Indução de Remissão , Estudos RetrospectivosRESUMO
Despite the clinical importance of health-related quality of life (QOL) in patients suffering from myelodysplastic syndromes (MDS), few data exist on the prevalence of key MDS-associated symptoms, or the correlation of those symptoms with specific disease features such as hemoglobin level. In order to better understand the burden of disease-associated symptoms in patients with MDS, we designed a 120-question Internet-based survey of QOL appropriate for patients with MDS, incorporating validated QOL measurement instruments and questions about specific therapies. The 359 survey respondents were typical of MDS patients in terms of demographics, blood counts, and disease subtype. Patients reported high levels of excessive fatigue and poor scores on QOL assessments such as the Functional Assessment of Cancer Therapy-Anemia (FACT-An) and the Brief Fatigue Inventory (BFI). Patients' debilitating fatigue correlated poorly with hemoglobin level, and fatigue was associated with significant impairment of both health-related QOL and ability to work or participate in desired activities. Within the limitations of self-reported data, these results provide a benchmark for future interventions to improve QOL in patients with MDS.
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Síndromes Mielodisplásicas/psicologia , Qualidade de Vida , Adulto , Idoso , Idoso de 80 Anos ou mais , Darbepoetina alfa , Epoetina alfa , Eritropoetina/efeitos adversos , Eritropoetina/análogos & derivados , Exantema/induzido quimicamente , Exantema/psicologia , Fadiga/etiologia , Fadiga/psicologia , Feminino , Hemoglobinas/análise , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/sangue , Síndromes Mielodisplásicas/tratamento farmacológico , Proteínas RecombinantesRESUMO
Mayo Clinic Scottsdale has extended the concept of an integrated, multispecialty clinical practice to the management of information technology. This adaptation of a traditional patient care model has been highly successful in a recent decade of extensive technology investment and deployment that has culminated in a paperless, filmless multicampus electronic medical record to support the mission of the clinic.
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Sistemas de Informação em Atendimento Ambulatorial/organização & administração , Prática de Grupo/organização & administração , Sistemas de Informação Hospitalar/organização & administração , Hospitais de Prática de Grupo/organização & administração , Medicina/organização & administração , Modelos Organizacionais , Especialização , Integração de Sistemas , Centros Médicos Acadêmicos/organização & administração , Arizona , Humanos , Sistemas Computadorizados de Registros Médicos , Estudos de Casos Organizacionais , Objetivos Organizacionais , Administração da Prática Médica , Comitê de ProfissionaisRESUMO
Rarely does an organization have the luxury of employing full-time staff whose sole purpose is to seek out, select, pilot, and recommend new technology. If such an effort is not a dedicated activity, an organization will have a hard time keeping abreast of technological development with an eye towards successful deployment to the benefit of the business. This paper summarizes the role and activities of the Office of Advanced Technology (OAT) at the Mayo Clinic in Scottsdale, AZ. The OAT has been in existence since 2001 and is staffed on a part-time basis by three individuals: a member of the physician consulting staff, a nurse informaticist, and a member of the allied health Information Technology staff. The office has successfully conducted pilot projects in several new technology areas, advocating the adoption of some technologies and deferring on others. Moreover, they have been instrumental serving as a spokesperson and single point of contact for all new technology initiatives of this multi-specialty practice.
Assuntos
Instituições de Assistência Ambulatorial/organização & administração , Avaliação da Tecnologia Biomédica , Projetos Piloto , Estados UnidosRESUMO
Interferon- α (IFN-α) alone or in combination with other chemotherapeutic agents has been used in the management of many malignant and non-malignant conditions. Pericarditis with or without pericardial effusion has been reported with IFN-α therapy, and available literature is limited to case reports. Pericardial constriction after interferon use has not been described in the published literature to date. We performed a systematic review of literature to address the demographic features, clinical presentation, diagnosis, treatment and outcome of interferon-related pericardial injury.
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OBJECTIVES: Few effective options are available for the treatment of unresectable hepatocellular carcinoma (HCC). Several phase I trials suggest promising activity of a combination of gemcitabine and docetaxel. METHODS: Patients with unresectable or metastatic HCC were treated with docetaxel 40 mg/m (later reduced to 30 mg/m) and gemcitabine 800 mg/m on days 1 and 8 every 3 weeks. Twenty-five patients were enrolled in 26 months. Median age was 64 (range, 27-078), 17 were male, 14 had liver-only disease, and 11 had extrahepatic disease. RESULTS: Of 25 patients evaluable for the primary end point (response), 2 (8%) have a confirmed partial response. The median time to progression is 2.76 months (95% confidence interval, 1.84-6.64 mo). Median survival was 12.8 months (95% confidence interval, 5.26-28.00). Two patients died on study owing to adverse events (1 hepatic and 1 renal failure), neither of which were attributed to the study medications. Twenty patients (81%) have experienced grade 3+ adverse events, including 11 with grade 4+ adverse events, primarily neutropenia, thrombocytopenia, diarrhea, and fatigue. CONCLUSIONS: Although this combination seems to have potential benefit, as measured by overall survival, its toxicity and the recent introduction of sorafenib has further limited the use of chemotherapy. Approaches other than chemotherapy are likely to be of the greatest potential benefit.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Carcinoma Hepatocelular/mortalidade , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Docetaxel , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Taxa de Sobrevida , Taxoides/administração & dosagem , Distribuição Tecidual , Resultado do Tratamento , GencitabinaRESUMO
The prognosis for patients with Philadelphia-negative myeloproliferative neoplasms (MPN) who evolve into acute myeloid leukemia (AML) or blast phase (MPN-BP) is extremely poor. Although allogeneic stem cell transplantation (allo-SCT) is considered potentially curative, very few patients have been reported who have undergone allo-SCT for MPN-BP; therefore the success rate remains unknown. In a retrospective review, we identified 13 patients with an MPN transformation to blast phase after a median 9 years (range 5 months to 30 years); 8 (median age 55) continued to allo-SCT within 6 months. Induction chemotherapy cleared blood/marrow blasts in 60% (6/10) (2 declined therapy, 1 had early death). At the time of allo-SCT, 5/8 patients were in complete remission (CR) of their leukemia or had returned to MPN chronic phase (CP), 2 had residual blood blasts and 1 was refractory with >5% marrow blasts. At follow-up (median 20.3 months), 6 patients are alive in CR of both their leukemia/MPN. All 5 patients in CR/CP at pre-allo-SCT remain alive in remission, while 2/3 with persistent blood/marrow blasts relapsed and expired. We conclude that MPN-BP can be cured by allo-SCT in a significant percentage of patients, but that adequate leukemic clearance prior to allo-SCT offers an optimal outcome.
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Crise Blástica/terapia , Neoplasias Hematológicas/terapia , Transtornos Mieloproliferativos/patologia , Transtornos Mieloproliferativos/terapia , Transplante de Células-Tronco/métodos , Adulto , Idoso , Feminino , Seguimentos , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Mieloproliferativos/diagnóstico , Transtornos Mieloproliferativos/genética , Indução de Remissão , Estudos Retrospectivos , Transplante Homólogo , Resultado do TratamentoRESUMO
PURPOSE The phosphatidylinositol 3-kinase/mammalian target of rapamycin (mTOR) signal transduction pathway controls cell proliferation and survival. Everolimus is an oral agent targeting raptor mTOR (mTORC1). The trial's goal was to determine the antitumor activity and safety of single-agent everolimus in patients with relapsed/refractory Waldenström macroglobulinemia (WM). PATIENTS AND METHODS Eligible patients had measurable disease (immunoglobulin M monoclonal protein > 1,000 mg/dL with > 10% marrow involvement or nodal masses > 2 cm), a platelet count more than 75,000 x 10(6)/L, a neutrophil count more than 1,000 x 10(6)/L, and a creatinine and bilirubin less than 2 x the laboratory upper limit of normal. Patients received everolimus 10 mg orally daily and were evaluated monthly. Tumor response was assessed after cycles 2 and 6 and then every three cycles until progression. Results Fifty patients were treated. The median age was 63 years (range, 43 to 85 years). The overall response rate (complete response plus partial remission [PR] plus minimal response [MR]) was 70% (95% CI, 55% to 82%), with a PR of 42% and 28% MR. The median duration of response and median progression-free survival (PFS) have not been reached. The estimated PFS at 6 and 12 months is 75% (95% CI, 64% to 89%) and 62% (95% CI, 48% to 80%), respectively. Grade 3 or higher related toxicities were observed in 56% of patients. The most common were hematologic toxicities with cytopenias. Pulmonary toxicity occurred in 10% of patients. Dose reductions due to toxicity occurred in 52% of patients. CONCLUSION Everolimus has high single-agent activity with an overall response rate of 70% and manageable toxicity in patients with relapsed WM and offers a potential new therapeutic strategy for this patient group.
Assuntos
Imunossupressores/uso terapêutico , Sirolimo/análogos & derivados , Macroglobulinemia de Waldenstrom/tratamento farmacológico , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Farmacológicos/sangue , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Everolimo , Feminino , Humanos , Imunoglobulina M/sangue , Imunossupressores/efeitos adversos , Imunossupressores/farmacologia , Masculino , Pessoa de Meia-Idade , Recidiva , Sirolimo/efeitos adversos , Sirolimo/farmacologia , Sirolimo/uso terapêutico , Análise de Sobrevida , Tomografia Computadorizada por Raios X , Macroglobulinemia de Waldenstrom/patologiaAssuntos
Antineoplásicos/uso terapêutico , Mielofibrose Primária/tratamento farmacológico , Pirazóis/uso terapêutico , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Aprovação de Drogas , Humanos , Janus Quinases/antagonistas & inibidores , Nitrilas , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Pirimidinas , Resultado do Tratamento , Estados Unidos , United States Food and Drug AdministrationRESUMO
Quality of life (QoL) in patients with myelofibrosis (MF) is severely compromised by severe constitutional symptoms (i.e. fatigue, night sweats, fever, weight loss), pruritus, and symptoms from frequently massive hepatosplenomegaly. Given that no current instrument of patient reported outcomes (PRO) exists that covers the unique spectrum of symptomatology seen in MF patients, we sought to develop a new PRO instrument for MF patients for use in therapeutic clinical trials. Utilizing data from an international Internet-based survey of 458 patients with MF we created a 20-item instrument (MFSAF: Myelofibrosis Symptom Assessment Form) which measures the symptoms reported by >10% of MF patients and includes a measure of QoL. We subsequently validated the MFSAF in a prospective trial of MF patients involving patient and provider feedback, as well as comparison to other validated instruments used in cancer patients. The MFSAF results were highly correlated with other instruments, judged comprehensive and understandable by patients, and should be considered for evaluation of MF symptoms in therapeutic trials.
Assuntos
Mielofibrose Primária/terapia , Qualidade de Vida , Humanos , Mielofibrose Primária/fisiopatologia , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Hepatocellular carcinoma (HCC) is a common cancer in certain portions of the world. Currently no effective therapies exist for patients with advanced or metastatic HCC. KW-2189, a DNA minor groove-binding agent, has shown promising activity against HCC in preclinical evaluations. METHODS: A phase II study was conducted to evaluate the activity of KW-2189 in patients with histologic or cytologic confirmed advanced or metastatic HCC who had no prior systemic therapy. Patients received KW-2189 at a dose of 0.5 mg/m2 administered on day 1 of a 6-week cycle. The primary endpoint of the trial was objective regression. Other endpoints included toxicity, disease-free survival, and overall survival. RESULTS: Due to hematologic toxicity the dose of KW-2189 was reduced to 0.375 mg/m2 after 11 patients had been enrolled into the trial. Due to continued significant hematologic toxicity in the next five patients enrolled at the lower dose the trial was closed to accrual. Two responses were seen in patients enrolled at the higher dose, including one sustained CR. CONCLUSION: KW-2189 showed evidence of anti-tumor activity in HCC. However, because of significant and prolonged hematologic toxicity, when given as a single dose every 6 weeks, further development of this drug in HCC is not possible. Further exploration of DNA minor groove-binding agents in the treatment of HCC appears warranted.