Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 11 de 11
Filtrar
1.
Qual Life Res ; 32(1): 183-196, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36029412

RESUMO

PURPOSE: Trial E1609 demonstrated superior overall survival with ipilimumab 3 mg/kg (ipi3) compared to high-dose interferon (HDI) for patients with resected high-risk melanoma. To inform treatment tolerability, we compared health-related quality of life (HRQoL), gastrointestinal (GI), and treatment-specific physical and cognitive/emotional symptoms. We also compared treatment-specific concerns between all arms. METHODS: We assessed HRQoL using the Functional Assessment of Cancer Therapy-General, physical and cognitive/emotional concerns using the FACT-Biologic Response Modifier subscale, and GI symptoms with the Functional Assessment of Chronic Illness Therapy-Diarrhea subscale pre-treatment and every 3 months. The primary outcome was the difference in HRQoL at 3 months between ipi3/ipi10 vs. HDI. RESULTS: 549 patients (n = 158 ipi3; n = 191 ipi10; n = 200 HDI) were analyzed. 3-month completion was 58.7%. Compared to HDI, ipilimumab patients reported better HRQoL (ipi3 = 87.5 ± 14.6 vs. HDI = 74.7 ± 15.4, p < .001; ipi10 = 84.9 ± 16.5 vs. HDI, p < .001) and fewer physical (ipi3 = 22.3 ± 4.6 vs. HDI = 17.1 ± 5.4, p < .001; ipi10 = 21.8 ± 5.0 vs. HDI p < .001) and cognitive/emotional (ipi3 = 18.6 ± 4.4 vs. HDI = 15.0 ± 5.3, p < .001; ipi10 = 17.7 ± 4.8 vs. HDI p < .001) concerns, but worse GI symptoms (ipi3 = 40.8 ± 5.0 vs. HDI = 42.2 ± 2.9, p = .011; ipi10 = 39.5 ± 7.0 vs. HDI, p < .001). Fewer ipilimumab patients reported worsening treatment-specific concerns (e.g., 52% of ipi3 and 58% of ipi10 reported worsening fatigue vs. 82% HDI, p's < .001). CONCLUSION: PROs demonstrated less toxicity of ipi3 compared to HDI and ipi10. Priorities for symptom management among patients receiving ipilimumab include GI toxicities, fatigue, weakness, appetite loss, arthralgia, and depression. TRIAL REGISTRATION: NCT01274338, January 11, 2011 (first posted date) https://clinicaltrials.gov/ct2/show/NCT01274338?term=NCT01274338&draw=2&rank=1 .


Assuntos
Melanoma , Qualidade de Vida , Humanos , Ipilimumab/efeitos adversos , Interferon alfa-2/uso terapêutico , Qualidade de Vida/psicologia , Estadiamento de Neoplasias , Melanoma/tratamento farmacológico , Melanoma/cirurgia , Medidas de Resultados Relatados pelo Paciente , Melanoma Maligno Cutâneo
2.
Am J Obstet Gynecol ; 227(1): 61.e1-61.e18, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35216968

RESUMO

BACKGROUND: Risk-reducing salpingo-oophorectomy is an effective ovarian cancer risk reduction strategy. However, bilateral oophorectomy has also been associated with increased long-term nonneoplastic sequelae, effects suggested to be mediated through reductions in systemic sex steroid hormone levels. Currently, it is unclear whether the postmenopausal ovary contributes to the systemic hormonal milieu or whether postmenopausal ovarian volume or other factors, such as body mass index and age, affect systemic hormone levels. OBJECTIVE: We examined the impact of oophorectomy on sex steroid hormone levels in postmenopausal women. Furthermore, we explored how well ovarian volume measured by transvaginal ultrasound correlated with direct ovarian measures obtained during surgical pathology evaluation and investigated the association between hormone levels and ovarian volumes. STUDY DESIGN: Postmenopausal women who underwent risk-reducing salpingo-oophorectomy (180 cases) or ovarian cancer screening (38 controls) enrolled in an international, prospective study of risk-reducing salpingo-oophorectomy and risk of ovarian cancer algorithm-based screening among women at increased risk of ovarian cancer (Gynecologic Oncology Group-0199) were included in this analysis. Controls were frequency matched to the cases on age at menopause, age at study entry, and time interval between blood draws. Ovarian volume was calculated using measurements obtained from transvaginal ultrasound in both cases and controls and measurements recorded in surgical pathology reports from cases. Serum hormone levels of testosterone, androstenedione, androstenediol, dihydrotestosterone, androsterone, dehydroepiandrosterone, estrone, estradiol, and sex hormone-binding globulin were measured at baseline and follow-up. Spearman correlation coefficients were used to compare ovarian volumes as measured on transvaginal ultrasound and pathology examinations. Correlations between ovarian volumes by transvaginal ultrasound and measured hormone levels were examined using linear regression models. All models were adjusted for age. Paired t tests were performed to evaluate individual differences in hormone levels before and after risk-reducing salpingo-oophorectomy. RESULTS: Ovarian volumes measured by transvaginal ultrasound were only moderately correlated with those reported on pathology reports (Spearman rho [ρ]=0.42). The median time interval between risk-reducing salpingo-oophorectomy and follow-up for the cases was 13.3 months (range, 6.0-19.3), and the median time interval between baseline and follow-up for the controls was 12.7 months (range, 8.7-13.4). Sex steroid levels decreased with age but were not correlated with transvaginal ultrasound ovarian volume, body mass index, or time since menopause. Estradiol levels were significantly lower after risk-reducing salpingo-oophorectomy (percentage change, -61.9 post-risk-reducing salpingo-oophorectomy vs +15.2 in controls; P=.02), but no significant differences were seen for the other hormones. CONCLUSION: Ovarian volumes measured by transvaginal ultrasound were moderately correlated with volumes directly measured on pathology specimens and were not correlated with sex steroid hormone levels in postmenopausal women. Estradiol was the only hormone that declined significantly after risk-reducing salpingo-oophorectomy. Thus, it remains unclear whether the limited post-risk-reducing salpingo-oophorectomy changes in sex steroid hormones among postmenopausal women impact long-term adverse outcomes.


Assuntos
Neoplasias Ovarianas , Salpingo-Ooforectomia , Estradiol , Feminino , Hormônios Esteroides Gonadais , Humanos , Neoplasias Ovarianas/prevenção & controle , Pós-Menopausa , Estudos Prospectivos
3.
J Immunother Cancer ; 6(1): 19, 2018 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-29510745

RESUMO

BACKGROUND: Despite improved survival following checkpoint inhibitors, there is still a potential role for anti-cancer therapeutic vaccines. Because of biological heterogeneity and neoantigens resulting from each patient's mutanome, autologous tumor may be the best source of tumor-associated antigens (TAA) for vaccines. Ex vivo loading of autologous dendritic cells with TAA may be associated with superior clinical outcome compared to injecting irradiated autologous tumor cells. We conducted a randomized phase II trial to compare autologous tumor cell vaccines (TCV) and autologous dendritic cell vaccines (DCV) loaded with autologous TAA. METHODS: Short-term autologous tumor cell lines were established from metastatic tumor. Vaccines were admixed with 500 micrograms of GM-CSF and injected weekly for 3 weeks, then at weeks 8, 12,16, 20, and 24. The primary endpoint was overall survival. Secondary objectives were identification of adverse events, and results of delayed type hypersensitivity (DTH) reactions to intradermal tumor cell injections. RESULTS: Forty-two patients were randomized. All were followed from randomization until death or for five years; none were lost to follow-up. DCV was associated with longer survival: median 43.4 versus 20.5 months (95% CI, 18.6 to > 60 versus 9.3 to 32.3 months) and a 70% reduction in the risk of death (hazard ratio = 0.304, p = 0.0053, 95% CI, 0.131 to 0.702). Tumor DTH reactions were neither prognostic nor predictive. The most common treatment-related adverse events were mild to moderate local injection site reactions and flu-like symptoms; but grade 2 treatment-related adverse events were more frequent with TCV. Serum marker analyses at week-0 and week-4 showed that serum markers were similar at baseline in each arm, but differed after vaccination. CONCLUSIONS: This is the only human clinical trial comparing DCV and TCV as platforms for autologous TAA presentation. DCV was associated with minimal toxicity and long-term survival in patients with metastatic melanoma. DTH to autologous tumor cells was neither prognostic for survival nor predictive of benefit for either vaccine. TRIAL REGISTRATION: Clinical trials.gov NCT00948480 retrospectively registered 28 July 2009.


Assuntos
Vacinas Anticâncer/uso terapêutico , Células Dendríticas/transplante , Melanoma/terapia , Citocinas/sangue , Feminino , Humanos , Hipersensibilidade Tardia , Masculino , Melanoma/sangue , Pessoa de Meia-Idade , Análise de Sobrevida , Transplante Autólogo/efeitos adversos
4.
Cancer Biother Radiopharm ; 30(5): 187-94, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26083950

RESUMO

In patients with metastatic melanoma, sequential single-arm and randomized phase II trials with a therapeutic vaccine consisting of autologous dendritic cells (DCs) loaded with antigens from self-renewing, proliferating, irradiated autologous tumor cells (DC-TC) showed superior survival compared with similar patients immunized with irradiated tumor cells (TC). We wished to determine whether this difference was evident in cohorts who at the time of treatment had (1) no evidence of disease (NED) or (2) had detectable disease. Eligibility criteria and treatment schedules were the same for all three trials. Pooled data confirmed that overall survival (OS) was longer in 72 patients treated with DC-TC compared with 71 patients treated with TC (median OS 60 versus 22 months; 5-year OS 51% versus 32%, p=0.004). Treatment with DC-TC was associated with longer OS in both cohorts. Among 70 patients who were NED at the time that treatment was started, OS was better for DC-TC: 5-year OS 73% versus 43% (p=0.015). Among 73 patients who had detectable metastases, OS was better for DC-TC: median 38.8 months versus 14.7 months, 5-year OS 33% versus 20% (p=0.025). This approach is promising as an adjunct to other therapies in patients who have had metastatic melanoma.


Assuntos
Vacinas Anticâncer/uso terapêutico , Células Dendríticas/transplante , Imunoterapia/métodos , Melanoma/terapia , Células-Tronco Neoplásicas/transplante , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapia , Carga Tumoral , Apresentação de Antígeno , Células Dendríticas/imunologia , Feminino , Fator Estimulador de Colônias de Granulócitos e Macrófagos/administração & dosagem , Humanos , Interferon gama/administração & dosagem , Masculino , Melanoma/imunologia , Melanoma/secundário , Antígenos Específicos de Melanoma/imunologia , Pessoa de Meia-Idade , Células-Tronco Neoplásicas/imunologia , Neoplasias Cutâneas/imunologia , Taxa de Sobrevida , Células Tumorais Cultivadas/imunologia
5.
Anticancer Res ; 35(1): 301-9, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25550564

RESUMO

BACKGROUND/AIM: Sentinel lymph node (SLN) biopsy provides useful prognostic information for patients with melanoma. The present study sought to determine the prognostic value of SLN tumor burden on overall survival (OS) and disease-free survival (DFS). We also assessed its association with non-sentinel lympth node (NSLN) involvement. PATIENTS AND METHODS: We conducted a retrospective review of 138 patients with cutaneous melanoma, who were found to have positive SLNs from 2000 to 2011. SLN tumor burden was measured in the maximum diameter of the largest tumor focus. OS and DFS were assessed by the Kaplan-Meier method and Cox proportional hazard regression model. A logistic regression model was used to evaluate the association between SLN tumor burden and NSLN positivity. RESULTS: On multivariable analysis, SLN tumor burden was significantly associated with OS (hazard ratio (HR)>1 vs. ≤ 1 mm=5.15; 95% confidence interval (CI)=2.32-11.44; p<0.0001) and DFS rate (HR>1 vs. ≤ 1 mm=3.02; 95% CI=1.37-6.67; p=0.0064). On univariate analysis, SLN tumor burden was significantly associated with NSLN positivity (OR>1 vs. ≤ 1 mm=3.41; 95% CI=1.03-11.27; p=0.04). CONCLUSION: SLN tumor burden, by measuring the maximum diameter of the largest tumor focus, is significantly associated with OS, DFS and NSLN involvement.


Assuntos
Melanoma/secundário , Neoplasias Cutâneas/patologia , Adulto , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Melanoma/mortalidade , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Biópsia de Linfonodo Sentinela , Neoplasias Cutâneas/mortalidade , Carga Tumoral
6.
Cancer ; 119(3): 586-92, 2013 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-22915053

RESUMO

BACKGROUND: Increasing evidence shows chemotherapy in combination with vascular endothelial growth factor (VEGF) inhibition is a clinically active therapy for patients with metastatic melanoma (MM). METHODS: A phase 2 trial was conducted in chemotherapy-naive patients with unresectable stage IV MM who were randomized to temozolomide (200 mg/m(2) on days 1 through 5) and bevacizumab (10 mg/kg intravenously on days 1 and 15) every 28 days (Regimen TB) or nab-paclitaxel (100 mg/m(2) , or 80 mg/m(2) post-addendum 5 secondary to toxicity, on days 1, 8, and 15), bevacizumab (10 mg/kg on days 1 and 15), and carboplatin (area under the curve [AUC] 6 on day 1, or AUC 5 post-addendum 5) every 28 days (Regimen ABC). Accrual goal was 41 patients per regimen. The primary aim of this study was to estimate progression-free survival rate at 6 months (PFS6) in each regimen. A regimen would be considered promising if its PFS6 rate was > 60%. RESULTS: Ninety-three eligible patients (42 TB and 51 ABC) were enrolled. The majority of patients had M1c disease (20 TB and 26 ABC). The median PFS and overall survival times with ABC were 6.7 months and 13.9 months, respectively. Median PFS time and median overall survival with TB were 3.8 months and 12.3 months, respectively. The most common severe toxicities (≥ grade 3) in both regimens were cytopenias, fatigue, and thrombosis. Among the first 41 patients enrolled onto each regimen, PFS6 rate was 32.8% (95% confidence interval: 21.1%-51.2%) for TB and 56.1% (90% confidence interval: 44.7%-70.4%) for ABC. CONCLUSIONS: The addition of bevacizumab to nab-paclitaxel and carboplatin shows promising activity despite tolerability issues.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Melanoma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Albuminas/administração & dosagem , Albuminas/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Dacarbazina/administração & dosagem , Dacarbazina/efeitos adversos , Dacarbazina/análogos & derivados , Feminino , Humanos , Masculino , Melanoma/mortalidade , Melanoma/patologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Análise de Sobrevida , Temozolomida , Resultado do Tratamento , Adulto Jovem
7.
J Immunother ; 35(8): 641-9, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22996370

RESUMO

Only 10% of metastatic melanoma patients survive 5 years, even though many can achieve substantial tumor reduction by surgical resection and/or radiation therapy and/or systemic therapy. An effective, nontoxic, consolidation immunotherapy could benefit such patients. We initiated a randomized trial to compare 2 promising patient-specific immunotherapy cell products. Patients had to have a diagnosis of metastatic melanoma and availability of an autologous melanoma cell line. Patients were stratified by whether their most advanced stage had been regional or distant metastases, and by whether they had measurable disease at the time of treatment, then they were randomized to receive irradiated autologous proliferating tumor cells or autologous dendritic cells (DC) loaded with antigens from such cells. Both products were injected subcutaneously in 500 µg of granulocyte-macrophage colony stimulating factor, weekly for 3 weeks and then monthly for 5 months. Patients in the 2 arms did not differ in baseline characteristics. All patients received prescribed therapy. Treatment was well tolerated. At the time of initial analysis, with no patients lost to follow-up, 50% of patients deceased, and all surviving patients followed for at least 6 months after randomization, survival is superior in the DC arm (hazard ratio, 0.27; 95% confidence interval, 0.098-0.729) with median survival not reached versus 15.9 months, and 2-year survival rates of 72% versus 31% (P=0.007). This trial provides evidence that a DC vaccine is associated with longer survival compared with a tumor cell vaccine, and is consistent with previous data suggesting a survival benefit from this patient-specific immunotherapy.


Assuntos
Vacinas Anticâncer/uso terapêutico , Células Dendríticas/transplante , Imunoterapia/métodos , Melanoma/terapia , Células-Tronco Neoplásicas/transplante , Neoplasias Cutâneas/terapia , Antígenos de Neoplasias/imunologia , Antígenos de Neoplasias/metabolismo , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Feminino , Seguimentos , Fator Estimulador de Colônias de Granulócitos e Macrófagos/administração & dosagem , Humanos , Masculino , Melanoma/imunologia , Melanoma/secundário , Pessoa de Meia-Idade , Células-Tronco Neoplásicas/imunologia , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/patologia , Análise de Sobrevida
8.
Clin Cancer Res ; 16(8): 2402-8, 2010 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-20371696

RESUMO

PURPOSE: Molecular biomarkers in blood are promising for assessment of tumor progression and treatment response. We hypothesized that serial monitoring of circulating tumor cells (CTC) with the use of multimarker quantitative real-time reverse transcriptase-PCR assays could be a surrogate predictor of outcome for melanoma patients enrolled in a multicenter phase II clinical trial of biochemotherapy (BCT) combined with maintenance biotherapy (mBT). EXPERIMENTAL DESIGN: Blood specimens were collected from 87 patients before and during induction BCT and mBT for stage IV melanoma. Expression of five melanoma-associated CTC biomarkers (MART-1, GalNAc-T, PAX-3, MAGE-A3, and Mitf) was assessed by quantitative real-time reverse transcriptase-PCR, and correlated with treatment response and disease outcome. RESULTS: The number of positive CTC biomarkers decreased overall during induction BCT (P < 0.0001). CTC biomarker detection after two cycles of BCT was correlated with treatment response (P = 0.005) and overall survival (P = 0.001): an increase in the number of CTC biomarkers was associated with poor response (P = 0.006) and overall survival (P < 0.0001). Multivariate analyses with the use of a Cox proportional hazards model identified the change in CTC biomarkers after two cycles of BCT as an independent prognostic factor for disease progression (risk ratio, 12.6; 95% confidence interval, 4.78-33.4; P < 0.0001) and overall survival (risk ratio, 6.11; 95% confidence interval, 2.37-15.7; P = 0.0005). CONCLUSION: Serial monitoring of CTC during induction BCT may be useful for predicting therapeutic efficacy and disease outcome in patients receiving BCT and mBT for stage IV melanoma.


Assuntos
Biomarcadores Tumorais/genética , Melanoma/tratamento farmacológico , Células Neoplásicas Circulantes/patologia , RNA Neoplásico/genética , Neoplasias Cutâneas/tratamento farmacológico , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/metabolismo , Ensaios Clínicos Fase II como Assunto , Feminino , Humanos , Masculino , Melanoma/sangue , Melanoma/patologia , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Estudos Prospectivos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Indução de Remissão , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias Cutâneas/sangue , Neoplasias Cutâneas/patologia , Taxa de Sobrevida , Resultado do Tratamento , Adulto Jovem
9.
J Clin Oncol ; 24(19): 3157-63, 2006 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-16809738

RESUMO

PURPOSE: To determine the relapse-free survival, overall survival, and response rate of patients with stage III melanoma treated with neoadjuvant biochemotherapy in a multicenter setting. PATIENTS AND METHODS: Patients with pathologically proven stage III melanoma, either via clinical detection or sentinel lymph node positivity, were eligible for enrollment. Patients received two cycles of preoperative biochemotherapy followed by complete regional lymphadenectomy and two postoperative courses of biochemotherapy. The biochemotherapy regimen consisted of the following: cisplatin 20 mg/m2 on days 1 to 4, dacarbazine 800 mg/m2 on day 1 only, vinblastine 1.6 mg/m2 on days 1 to 4, interleukin-2 total dose of 36 MU/m2 during 4 days, and interferon alfa 5 MU/m2 on days 1 to 5. Growth factor support was administered with each cycle. RESULTS: Ninety-two patients were eligible for the study. At a median follow-up of 40.4 months, relapse-free survival and overall survival are 64% and 78%, respectively. There was a lower relapse rate and improved survival for patients with a positive sentinel lymph node compared with patients with clinically detected lymph nodes, although this difference did not reach statistical significance. Of the 50 patients with measurable disease, the overall response rate was 26%. Toxicity of the biochemotherapy was high but generally manageable. CONCLUSION: The current study has expanded the preliminary evidence on neoadjuvant biochemotherapy for stage III melanoma.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Melanoma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Adolescente , Adulto , Idoso , Cisplatino/administração & dosagem , Dacarbazina/administração & dosagem , Feminino , Humanos , Interferon-alfa/administração & dosagem , Interleucina-2/administração & dosagem , Excisão de Linfonodo , Masculino , Melanoma/patologia , Melanoma/cirurgia , Pessoa de Meia-Idade , Terapia Neoadjuvante , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia , Análise de Sobrevida , Vimblastina/administração & dosagem
10.
Clin Cancer Res ; 12(4): 1137-43, 2006 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-16489066

RESUMO

PURPOSE: Microphthalmia transcription factor (Mitf), which is important in melanocyte development and melanoma growth, was assessed using real-time quantitative reverse transcription-PCR assay to investigate its expression as a marker for circulating melanoma cells in blood and determine the correlation with disease stage and survival in melanoma patients. EXPERIMENTAL DESIGN: In optimization studies for Mitf, we tested 15 melanoma cell lines, 41 peripheral blood lymphocytes from healthy volunteers, and 21 metastatic melanoma tissues. Blood specimens were procured from 90 patients with stage I (n = 20), stage II (n = 20), stage III (n = 28), and stage IV (n = 22) melanoma. Blood specimens were also obtained at four bleed intervals from 58 patients enrolled in a prospective multicenter trial of biochemotherapy before and after surgical treatment of American Joint Committee on Cancer stage III melanoma. RESULTS: Under the optimized conditions, Mitf was negative in healthy peripheral blood lymphocytes and positive in all melanoma cell lines and 18 (86%) melanoma tissues. In the 90 patients, the rate of Mitf detection was higher with increasing American Joint Committee on Cancer stage (P < 0.0001). In the 58 patients treated with biochemotherapy and surgery, Mitf detection decreased with treatment (P = 0.019). Mitf detection after treatment was associated with a significantly lower relapse-free (P < 0.0001) and overall (P = 0.001) survival and was a significant independent prognostic factor for relapse-free (risk ratio, 5.63; P = 0.0004) and overall (risk ratio, 5.36; P = 0.005) survival. CONCLUSIONS: Mitf detection in blood can indicate subclinical metastatic disease and predict treatment outcome in melanoma patients.


Assuntos
Melanoma/sangue , Fator de Transcrição Associado à Microftalmia/genética , Células Neoplásicas Circulantes/metabolismo , Adolescente , Adulto , Idoso , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Feminino , Expressão Gênica , Humanos , Linfócitos/metabolismo , Masculino , Melanoma/patologia , Melanoma/terapia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Prognóstico , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sobrevida
11.
J Clin Oncol ; 23(31): 8057-64, 2005 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-16258104

RESUMO

PURPOSE: Circulating tumor cells (CTCs) in blood may be important in assessing tumor progression and treatment response. We hypothesized that quantitative real-time reverse transcriptase polymerase chain reaction using multimarker mRNA assays could detect CTCs and be used as a surrogate predictor of outcome in patients receiving neoadjuvant biochemotherapy (BC) for melanoma. PATIENTS AND METHODS: Blood specimens were collected at four sampling points from 63 patients enrolled on a prospective multicenter phase II trial of BC before and after surgical treatment of American Joint Committee on Cancer stage III melanoma. Each specimen was assessed by quantitative real-time reverse transcriptase polymerase chain reaction for expression of four melanoma-associated markers: melanoma antigen recognized by T cells 1; beta1 --> 4-N-acetylgalactosaminyltransferase; paired box homeotic gene transcription factor 3; and melanoma antigen gene-A3 family, and the changes of CTCs during treatment and prognostic effect of CTCs after overall treatment on recurrence and survival were investigated. RESULTS: At a median postoperative follow-up time of 30.4 months, 44 (70%) patients were clinically disease free. In relapse-free patients, the number of detected markers significantly decreased during preoperative BC (P = .036), during postoperative BC (P = .002), and during overall treatment (P < .0001). Marker detection after overall treatment was associated with significant decreases in relapse-free and overall survival (P < .0001). By multivariate analysis using a Cox proportional-hazards model, the number of markers detected after overall treatment was a significant independent prognostic factor for overall survival (risk ratio, 12.6; 95% CI, 3.16 to 50.5; P = .0003). CONCLUSION: Serial monitoring of CTCs in blood may be useful for indicating systemic subclinical disease and predicting outcome of patients receiving neoadjuvant BC for metastatic melanoma.


Assuntos
Antígenos de Neoplasias/sangue , Melanoma/sangue , Terapia Neoadjuvante , Recidiva Local de Neoplasia/sangue , Células Neoplásicas Circulantes/metabolismo , Neoplasias Cutâneas/sangue , Adolescente , Adulto , Idoso , Antígenos de Neoplasias/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/metabolismo , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Dacarbazina/administração & dosagem , Feminino , Humanos , Interferon-alfa/administração & dosagem , Interleucina-2/administração & dosagem , Antígeno MART-1 , Masculino , Melanoma/tratamento farmacológico , Melanoma/patologia , Pessoa de Meia-Idade , N-Acetilgalactosaminiltransferases/sangue , N-Acetilgalactosaminiltransferases/genética , Invasividade Neoplásica/patologia , Proteínas de Neoplasias/sangue , Proteínas de Neoplasias/genética , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Células Neoplásicas Circulantes/patologia , Fator de Transcrição PAX3 , Fatores de Transcrição Box Pareados/sangue , Fatores de Transcrição Box Pareados/genética , Estudos Prospectivos , RNA Mensageiro/sangue , RNA Mensageiro/genética , RNA Neoplásico/sangue , RNA Neoplásico/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Risco , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Taxa de Sobrevida , Resultado do Tratamento , Vimblastina/administração & dosagem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...