Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 15 de 15
Filtrar
1.
Exp Hematol ; 111: 79-86, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35417741

RESUMEN

Identifying effective combination regimens is a high priority in multiple myeloma (MM), as most patients eventually become refractory to their current treatments. In this study, we investigated whether the proteasome inhibitor (PI) ixazomib could delay disease progression among patients who failed regimens containing another PI, bortezomib or carfilzomib. This phase 1/2, multicenter, open-label, nonrandomized study enrolled patients who were refractory to a previous regimen containing bortezomib or carfilzomib. Patients continued the other anti-MM drugs in the regimen at the same doses and frequencies. Patients with combination regimens with unknown maximum tolerated dose (MTD) of ixazomib were enrolled in phase 1, with ixazomib starting at 3 mg and then dose escalated to 4 mg. Patients on regimens with a known ixazomib MTD were enrolled in phase 2. Primary endpoints were overall response rate (ORR), clinical benefit rate (CBR), adverse events (AEs), and determination of maximum tolerated dose (MTD). Of the 46 patients enrolled, 39 were evaluable for efficacy. ORR and CBR were 12.8% and 17.9%, respectively. Ixazomib appeared to be well tolerated as a replacement for carfilzomib and bortezomib, with 23.9% of patients experiencing at least one grade ≥3 serious adverse event (SAE) and 37.0% experiencing at least one grade ≥3 AE. The most common grade ≥3 AEs were hyponatremia (8.7%), anemia (8.7%), dyspnea (8.7%), thrombocytopenia (6.5%), dehydration (4.3%), and pneumonia (4.3%). The results indicate that ixazomib is not an effective replacement for bortezomib or carfilzomib for patients with MM who have previously relapsed on other bortezomib/carfilzomib-containing regimens.


Asunto(s)
Mieloma Múltiple , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Compuestos de Boro , Bortezomib , Dexametasona/efectos adversos , Glicina/análogos & derivados , Humanos , Mieloma Múltiple/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Oligopéptidos
2.
J Oncol Pract ; 15(12): e1076-e1084, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31573829

RESUMEN

PURPOSE: Addressing unwarranted clinical variation in oncology is a high priority for health systems that aspire to ensure consistent levels of high-quality and cost-effective care. Efforts to improve clinical practice and standardize care have proven challenging. Advocate Physician Partners undertook a patient simulation-based practice measurement and feedback project that was focused on breast and lung cancer to engage oncologists in the care standardization process. METHODS: One hundred three medical oncologists cared for online simulated patients using the Clinical Performance and Value platform, receiving feedback on how their care decisions compared with evidence-based guidelines and their peers. We repeated this process every 4 months over six rounds, measuring changes in quality-of-care scores. We then compared simulated patient results with available patient-level claims data. RESULTS: Over the course of the project, overall quality-of-care scores improved 11.9% (P < .001). Diagnostic accuracy increased 6.7% (P < .001) and correlated with improved treatment scores, including a nearly 10-percentage point increase in evidence-based chemotherapy regimens (P = .009) and a 56% increase in addressing palliative needs for patients with late-stage disease (P < .001). Unnecessary test ordering declined 25% (P < .001). We compared these results with available patient data and observed concordance with the metastatic imaging workup order rate for early-stage breast cancer. As unnecessary workups declined in the simulations and became more closely aligned with evidence-based guidelines, we saw similar rates of decline in the patient-level data. CONCLUSION: This study demonstrates that an oncology care standardization system that combines simulated patients with serial feedback increases evidence-based and cost-effective clinical decisions in patient simulations and patient-level data.


Asunto(s)
Neoplasias de la Mama/epidemiología , Análisis Costo-Beneficio/economía , Oncología Médica/economía , Calidad de la Atención de Salud , Neoplasias de la Mama/economía , Neoplasias de la Mama/terapia , Toma de Decisiones , Retroalimentación , Femenino , Adhesión a Directriz , Humanos , Médicos/economía
3.
Support Care Cancer ; 25(10): 3217-3224, 2017 10.
Artículo en Inglés | MEDLINE | ID: mdl-28455546

RESUMEN

OBJECTIVE: Neuropathy is an important complication that may limit treatment options for patients with multiple myeloma. Previous studies have focused on treatment efficacy and have shown that retreatment with bortezomib (BTZ) is an effective treatment option. The goal of this study was to focus on the clinical manifestations of peripheral neuropathy (PN) and to retrospectively compare the incidence and severity of PN between the initial BTZ regimen and upon retreatment. Furthermore, this study evaluated how certain factors affect BIPN, which will help determine what conditions should be considered prior to retreatment. METHODS: Charts were reviewed from 93 patients who were retreated with a BTZ-containing regimen after previously being treated with this drug. RESULTS: Among the patients who developed PN, most patients in the study had low-grade neuropathy during the initial BTZ treatment (n = 52, 68%). The results showed no evidence of cumulative toxicity, and there was no significant difference in the incidence and severity of PN upon retreatment. Factors such as the presence of baseline PN, number of prior treatments, dose of BTZ, and comorbidities did not increase the severity of PN upon retreatment. The lapse of time between the two regimens also did not affect the severity of PN. CONCLUSION: The results suggest that retreatment with BTZ may be a feasible option, without additional risks of PN, for MM patients even with peripheral neuropathy during their initial treatment with this drug.


Asunto(s)
Antineoplásicos/efectos adversos , Bortezomib/efectos adversos , Mieloma Múltiple/tratamiento farmacológico , Enfermedades del Sistema Nervioso Periférico/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/administración & dosificación , Bortezomib/administración & dosificación , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Mieloma Múltiple/complicaciones , Mieloma Múltiple/epidemiología , Enfermedades del Sistema Nervioso Periférico/epidemiología , Enfermedades del Sistema Nervioso Periférico/etiología , Enfermedades del Sistema Nervioso Periférico/patología , Recurrencia , Retratamiento , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Resultado del Tratamiento
4.
Clin Genitourin Cancer ; 12(2): 100-5, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24169494

RESUMEN

BACKGROUND: Sorafenib promotes apoptosis through downstream pathways that can be deregulated in CRPC. We hypothesized that sorafenib could overcome chemotherapy resistance in CRPC. PATIENTS AND METHODS: Eligible patients were those whose disease had progressed during chemotherapy (docetaxel or mitoxantrone) or within 12 weeks of stopping either. Patients then continued or resumed their last chemotherapy regimen with the addition of sorafenib 400 mg twice daily. Patients received a maximum of 6 cycles of chemotherapy/sorafenib followed by sorafenib alone until disease progression. The primary end point was combination safety. Secondary end points were overall response, percentage of SD, and time to progression (TTP). RESULTS: Twenty-two patients (21 evaluable) were enrolled (16 patients with Gleason score ≥ 7). Median age was 68 years (range, 59-83 years). Median prostate-specific antigen (PSA) was 142 ng/dL (range, 13.6-9584). Visceral and bone disease were present combined in 9 patients (41%). Ten patients (47.6%) showed biochemical response (19% with > 50% PSA decline) and 16 patients (76%) achieved radiographic stability (according to Response Evaluation Criteria for Solid Tumors) after starting sorafenib for a median duration of 6 months (range, 4-12 months). Grade 3/4 nonhematologic toxicities were fatigue (n = 7, 32%), palmar-plantar erythrodysesthesia (n = 4, 18%). Dose reduction of sorafenib occurred at least once in 15 patients (68%) because of palmar-plantar erythrodysesthesia (22%) and fatigue (22%). With a median follow-up of 19 months (range, 3-46 months), median overall survival was 8 months. TTP according to PSA level was 3 months and TTP according to imaging studies and/or clinically was 6 months. Median number of treatment cycles given was 6 (range, 1-10). CONCLUSION: Sorafenib can be combined safely with chemotherapy and in some patients overcomes chemotherapy resistance.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Docetaxel , Resistencia a Antineoplásicos , Humanos , Masculino , Persona de Mediana Edad , Mitoxantrona/administración & dosificación , Niacinamida/administración & dosificación , Niacinamida/análogos & derivados , Compuestos de Fenilurea/administración & dosificación , Neoplasias de la Próstata Resistentes a la Castración/mortalidad , Sorafenib , Análisis de Supervivencia , Taxoides/administración & dosificación , Insuficiencia del Tratamiento
5.
Cancer ; 117(7): 1490-7, 2011 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-21425150

RESUMEN

BACKGROUND: Currently, no standard therapy exists for patients with relapsed and/or refractory non-Hodgkin lymphoma (NHL) who are ineligible for transplantation or who have failed after bone marrow transplantation. The authors of this report investigated the safety and efficacy of clofarabine (CLO) in these patients. METHODS: In a 2-step, open-label study, CLO (as a 1-hour intravenous infusion given daily for 5 days) was given every 28 days (maximum, 6 cycles). In the phase 1 portion (n = 7; standard 3 + 3 study design), the dose was escalated by 2 mg/m(2) to determine the maximum tolerated dose (MTD). The phase 2 study (n = 26) was initiated at the MTD, and patients were followed until disease progression. RESULTS: Of 33 patients who were enrolled, 31 patients (median age, 69 years) were evaluable; 24% failed after previous stem cell transplantation, and 72% were rituximab-refractory. The MTD for CLO was 4 mg/m(2) . The overall response rate was 42%. Seven patients (23%) achieved a complete response, and 6 patients (19%) achieved a partial response. The median response duration was 5 months. Among the rituximab-refractory patients, the overall response rate was 47% (complete response rate, 28%), and the median response duration was 7 months. At a median follow-up of 14 months, 45% of patients remained alive (median overall survival, 10 months). Toxicity was mainly hematologic (≥60% of patients had neutropenia or thrombocytopenia). Nonhematologic toxicity included tumor lysis syndrome, infection, and renal insufficiency (in 6% of patients each). No treatment-related mortality was observed. CONCLUSIONS: Single-agent CLO was active and was tolerated well in patients with refractory NHL, including patients in a rituximab-refractory subset. Reversible myelosuppression was the major toxicity. Study is registered at www.clinicaltrials.gov (NCT00156013).


Asunto(s)
Nucleótidos de Adenina/uso terapéutico , Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Arabinonucleósidos/uso terapéutico , Linfoma no Hodgkin/tratamiento farmacológico , Nucleótidos de Adenina/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Arabinonucleósidos/efectos adversos , Clofarabina , Supervivencia sin Enfermedad , Resistencia a Antineoplásicos , Femenino , Humanos , Linfoma no Hodgkin/mortalidad , Masculino , Persona de Mediana Edad , Recurrencia , Retratamiento , Rituximab , Terapia Recuperativa
7.
Avicenna J Med ; 1(1): 12-7, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23210004

RESUMEN

PURPOSE: To investigate the toxicity and efficacy of GM-CSF in castration-resistant prostate cancer (CRPC) patients who maximized their response to systemic chemotherapy. MATERIALS AND METHODS: CRPC patients who maximized their response to either docetaxel or mitoxantrone chemotherapy were eligible if they demonstrated adequate performance status, liver, kidney, and bone marrow function. Maximum response to chemotherapy was defined as either receiving at least 8 cycles of chemotherapy without radiographic or biochemical progression, receiving less than 8 cycles as long as the prostate-specific antigen (PSA) changes by less than 10%, or being off chemotherapy for less than 12 weeks without disease progression. Patients received GM-CSF at 250 mcg/m(2) subcutaneously for 14 days followed by 14 days of rest. GM-CSF was continued until disease progression. RESULTS: Fifteen patients were enrolled of which all were evaluable for toxicity and 13 were evaluable for efficacy. Median age was 78 (range 66-96) and 93% of patients had a Gleason score ≥ 7. Biochemically, 2 patients (15.3%) attained partial response (PR) and 4 (30.7%) had stable disease (SD). Median time to PSA progression was 6 months (range 4-12). Radiographically, 9 patients (69.2%) had SD that lasted a median of 6 months (range 2-10). With a median follow-up of 24 months from starting GM-CSF (range 2-38), 2 patients (13.3%) remain alive and well. Median OS from start of any chemotherapy was 21 months (range 10-44). GM-CSF was well-tolerated with minimal expected manageable toxicities. CONCLUSIONS: GM-CSF is active post-chemotherapy in CRPC patients. Further studies with GM-CSF in this setting are warranted.

8.
Biol Blood Marrow Transplant ; 16(1): 35-45, 2010 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-20053330

RESUMEN

We compared outcomes of 916 diffuse large B cell lymphoma (DLBCL) patients aged >or=18 years undergoing first autologous (n = 837) or myeloablative (MA) allogeneic hematopoietic cell transplant (HCT) (n = 79) between 1995 and 2003 reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). Median follow-up was 81 months for allogeneic HCT versus 60 months for autologous HCT. Allogeneic HCT recipients were more likely to have high-risk disease features including higher stage, more prior chemotherapy regimens, and resistant disease. Allogeneic HCT was associated with a higher 1 year treatment-related mortality (TRM) (relative risk [RR] 4.88, 95% confidence interval [CI], 3.21-7.40, P < .001), treatment failure (RR 2.06, 95% CI, 1.54-2.75, P < .001), and mortality (RR 2.75, 95% CI, 2.03-3.72, P < .001). Risk of disease progression was similar in the 2 groups (RR 1.12, 95% CI, 0.73-1.72, P = .59). In fact, for 1-year survivors, no significant differences were observed for TRM, progression, progression-free (PFS) or overall survival (OS). Increased risks of TRM and mortality were associated with older age (>50 years), lower performance score, chemoresistance, and earlier year of transplant. In a cohort of mainly high-risk DLBCL patients, upfront MA allogeneic HCT, although associated with increased early mortality, was associated with a similar risk of disease progression compared to lower risk patients receiving autologous HCT.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Linfoma de Células B Grandes Difuso/terapia , Hermanos , Adolescente , Adulto , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Trasplante de Células Madre Hematopoyéticas/mortalidad , Prueba de Histocompatibilidad , Humanos , Masculino , Persona de Mediana Edad , Sistema de Registros , Estudios Retrospectivos , Estadística como Asunto , Donantes de Tejidos , Trasplante Autólogo , Trasplante Homólogo , Resultado del Tratamiento , Adulto Joven
9.
Urology ; 74(3): 665-71, 2009 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-19616281

RESUMEN

OBJECTIVES: To investigate the efficacy and toxicity of single-agent erlotinib in chemotherapy-naive castration-resistant prostate cancer. METHODS: Eligible patients received erlotinib at 150 mg daily until disease progression. Toxicity was assessed every 2 weeks and responses every 8 weeks. Primary end point was assessing the overall clinical benefit measured as the sum of stable disease, partial response, and complete response. Secondary end points included time to disease progression, overall survival, and toxicity using the National Cancer Institute Common Toxicity Criteria version 3.0. RESULTS: A total of 29 patients were enrolled in this study. Median age was 77 and median prostate-specific antigen was 66.3 ng/mL. Of 22 evaluable patients, 2 met the criteria for partial response and 5 demonstrated stable disease for an overall clinical benefit of 31%. PSA-doubling time improved in all responding patients to a median of 6 months from 3 months before entry into the study. One patient remained in study at 28 months, and 2 had > 50% decrease in their serum PSA level. Median time to disease progression was 2 months, but at 12 months, 9% of patients were progression-free. Median overall survival was 16.3 months, with 1- and 2-year survival rates of 58% and 27%, respectively. Erlotinib was well tolerated, with only 2 patients requiring dose reductions. Adverse events were as expected with grade 3 or 4 diarrhea, fatigue, and rash occurring in 10%, 6%, and 6% of patients, respectively. CONCLUSIONS: Erlotinib has moderate activity in chemotherapy-naive castration-resistant prostate cancer, with some patients showing biochemical response. Future studies investigating this agent in combination are warranted. (This trial was registered at http://NCI.gov, NCT00272038).


Asunto(s)
Receptores ErbB/antagonistas & inhibidores , Neoplasias de la Próstata/tratamiento farmacológico , Quinazolinas/uso terapéutico , Anciano , Anciano de 80 o más Años , Antagonistas de Andrógenos/uso terapéutico , Resistencia a Antineoplásicos , Clorhidrato de Erlotinib , Humanos , Masculino , Persona de Mediana Edad
10.
Biol Blood Marrow Transplant ; 14(12): 1323-33, 2008 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19041053

RESUMEN

To compare the clinical outcomes of older (age > or =55 years) non-Hodgkin lymphoma (NHL) patients with younger NHL patients (<55 years) receiving autologous hematopoietic cell transplantation (HCT) while adjusting for patient-, disease-, and treatment-related variables, we compared autologous HCT outcomes in 805 NHL patients aged > or =55 years to 1949 NHL patients <55 years during the years 1990-2000 using data reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). In multivariate analysis, older patients with aggressive histologies were 1.86 times (95% confidence interval [CI] 1.43-2.43, P < .001) more likely than younger patients to experience treatment-related mortality (TRM). Relative death risks were 1.33 times (CI 1.04-1.71, P = .024) and 1.50 times (CI 1.33-16.9, P < .001) higher in older compared to younger patients with follicular grade I/II and aggressive histologies, respectively. Autologous HCT in older NHL patients is feasible, but most disease-related outcomes are statistically inferior to younger patients. Studies addressing supportive care particular to older patients, who are most likely to benefit from this approach, are recommended.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Linfoma no Hodgkin/mortalidad , Linfoma no Hodgkin/patología , Linfoma no Hodgkin/terapia , Adulto , Factores de Edad , Anciano , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia , Trasplante Autólogo
11.
Clin Colorectal Cancer ; 6(6): 436-41, 2007 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-17531107

RESUMEN

PURPOSE: Preoperative chemotherapy followed by surgery and adjuvant chemotherapy is a standard treatment for most patients with rectal cancer. We aimed to determine efficacy and tolerability of preoperative mitomycin, fluorouracil (5-FU), and leucovorin (LV) concurrent with hyperfractionated radiation therapy (RT) followed by surgery and adjuvant chemotherapy. PATIENTS AND METHODS: Patients with clinical stage II/III disease were treated with mitomycin 10 mg/m(2) on day 1, continuous venous infusion 5-FU 600 mg/m(2) per day for 96 hours, and oral LV 25 mg every 6 hours on days 1-5. All patients received concurrent RT in fractions of 150 cGy twice daily beginning on day 1. Unfixed tumors received 3000 cGy, whereas fixed tumors received a dose of 4500 cGy. Patients then underwent resection and postoperative adjuvant chemotherapy with oral LV and continuous venous infusion 5-FU 600 mg/m(2) per day on days 1-5 on a 28-day cycle for 6 cycles. Primary endpoints were to determine the rate of pathologic response and downstaging, long-term locoregional control, progression-free survival, and overall survival. RESULTS: Between the years 1993 and 2000, 83 patients were enrolled. Eighteen patients (31%) were downstaged. Six patients (7%) had pathologic complete response. Median follow-up was 62 months with a 5-year overall survival of 71%. Local control rate was 96%. Treatment was well tolerated with stomatitis, diarrhea, and radiation proctitis being the most common toxicities. CONCLUSION: This regimen is effective in the treatment of rectal carcinoma. The favorable toxicity profile of mitomycin and hyperfractionated RT allows these strategies to be utilized with the newer chemotherapies for this disease.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/radioterapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/radioterapia , Adenocarcinoma/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Femenino , Fluorouracilo/administración & dosificación , Humanos , Leucovorina/administración & dosificación , Masculino , Persona de Mediana Edad , Mitomicina/administración & dosificación , Terapia Neoadyuvante , Cuidados Preoperatorios/métodos , Radioterapia Adyuvante , Neoplasias del Recto/cirugía , Análisis de Supervivencia , Factores de Tiempo , Complejo Vitamínico B/administración & dosificación
15.
Biol Blood Marrow Transplant ; 9(6): 383-8, 2003 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-12813446

RESUMEN

Eleven elderly patients (older than 65 years) with relapsed large cell lymphoma were treated with high-dose myeloablative therapy and autologous peripheral blood progenitor cell support (ABMT). All 11 patients were in sensitive relapse at the time of ABMT. Treatment-related mortality was 9%. Median CD34 cell collection was 4.8 x 10(6) cells/kg. Median time to hematologic recovery was 11 days for granulocytes (range, 9 to 16 days) and 18 days for platelets (range, 14 to 42 days). Nine of 11 patients (81%) achieved a complete response following ABMT. Median time to treatment failure was 17 months. The 4-year disease-free and overall survival is projected to be 44%. When compared with a cohort of patients under age 65 years with sensitive relapsed large cell lymphoma treated with ABMT during the same time interval, disease-free and overall survival are comparable. ABMT is feasible, tolerable, and effective in elderly patients with relapsed large cell lymphoma with disease-free survival rates comparable to younger patients.


Asunto(s)
Linfoma de Células B Grandes Difuso/terapia , Trasplante de Células Madre de Sangre Periférica , Terapia Recuperativa , Acondicionamiento Pretrasplante , Factores de Edad , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Terapia Combinada , Supervivencia sin Enfermedad , Estudios de Factibilidad , Femenino , Humanos , Linfoma de Células B Grandes Difuso/mortalidad , Masculino , Recurrencia , Análisis de Supervivencia , Acondicionamiento Pretrasplante/efectos adversos , Acondicionamiento Pretrasplante/métodos , Trasplante Autólogo , Resultado del Tratamiento
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA