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1.
J Natl Compr Canc Netw ; 17(4): 358-364, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30959472

RESUMO

BACKGROUND: Chemotherapy-induced oral thermal hyperalgesia (OTH) is a common and debilitating side effect of platinum-based anticancer agents. This study evaluated the efficacy of oral cryotherapy in preventing OTH during oxaliplatin chemotherapy infusion. METHODS: Patients with gastrointestinal cancer treated with biweekly oxaliplatin (85 mg/m2 over 120 minutes) at Abramson Cancer Center at the University of Pennsylvania were randomized to receive oral cryotherapy (ice chips) during oxaliplatin infusion or standard-of-care treatment. All patients completed baseline questionnaires regarding oral and peripheral symptoms and on-treatment questionnaires on day 1 of each subsequent chemotherapy cycle. Those in the treatment arm were asked to document how long they kept the ice chips in their mouths (0, <30, 30, 60, 90, or 120 minutes) and to report their discomfort associated with oral cryotherapy. Evaluable patients were those who had completed at least 2 cycles of oxaliplatin therapy. RESULTS: Of 62 randomized patients with a variety of gastrointestinal malignancies, 50 (25 per treatment arm) were evaluable for efficacy. The rate of patients with oral symptoms after the first treatment cycle was significantly lower in the intervention arm (n=8; 32%) than in the control arm (n=18; 72%), meeting the primary study objective (P=.01). The magnitude of difference in symptom scores before versus after the first treatment cycle was significantly less in the intervention versus control arm (P=.001). No difference in oral symptoms over time was seen between the intervention and control groups (P=.20), although a high attrition rate was noted. Duration of ice chip exposure was associated with improved oral symptoms over time (P=.02). CONCLUSIONS: Oral cryotherapy is a tolerable and cost-effective method of diminishing OTH in patients receiving oxaliplatin chemotherapy, and seems to be most effective in the early stages of treatment.


Assuntos
Antineoplásicos/uso terapêutico , Crioterapia/métodos , Hiperalgesia/tratamento farmacológico , Oxaliplatina/uso terapêutico , Administração Oral , Adulto , Idoso , Antineoplásicos/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oxaliplatina/farmacologia
2.
Cancer ; 118(23): 5783-92, 2012 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-22569917

RESUMO

BACKGROUND: Detailed information about how patients with head and neck carcinoma (HNC) are treated across practice settings does not exist. The authors conducted a prospective, observational study to examine the patterns of care for a series of patients with newly diagnosed HNC in the United States and to test 2 hypotheses: 1) There is no difference in the pattern of care between community and academic settings; and 2) the results of major randomized clinical trials will change the pattern of care in both practice settings within 1 year of publication in peer-reviewed journals. METHODS: Patients aged ≥ 18 years were enrolled in the Longitudinal Oncology Registry of Head and Neck Carcinoma (LORHAN) after providing written informed consent if they had a confirmed diagnosis of new HNC and were scheduled to receive treatment other than surgery alone. RESULTS: Between 2005 and 2010, 100 centers enrolled 4243 patients, including 2612 patients (62%) from academic investigators and 1631 patients (38%) from community centers. Initial treatments were radiation with concurrent chemotherapy (30%) or cetuximab (9%), adjuvant radiotherapy (21%), induction chemotherapy (16%), and other (24%). Intensity modulated radiation therapy was the dominant radiation technique (84%). Single-agent cisplatin was prescribed in nearly half of patients and more often in academic centers (53% vs 43% of patients; P < .0001). Single-agent cetuximab was the next most common drug used (19%) and was prescribed more frequently in community settings (24% vs 17%; P = .0001). The data rejected the 2 prospective hypotheses. CONCLUSIONS: LORHAN documented differences in patient characteristics and treatments between community and academic settings for a large series of patients in the United States.


Assuntos
Neoplasias de Cabeça e Pescoço/epidemiologia , Sistema de Registros , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimiorradioterapia , Ensaios Clínicos como Assunto , Feminino , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estados Unidos/epidemiologia
3.
Surgery ; 171(6): 1473-1479, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34862070

RESUMO

BACKGROUND: Adjuvant systemic therapy is selectively considered for high-risk stage II colon cancer, but which patients benefit most from adjuvant systemic therapy is unclear. METHODS: Patients who underwent resection of stage II colon cancer were identified from the National Cancer Database (2010-2016). Risk-factors for decreased overall survival on multivariable analysis were used to establish a predictive risk-score model for all-cause mortality. After propensity matching within each risk group, 5-year overall survival was estimated based on receipt of adjuvant systemic therapy. RESULTS: Of the 15,241 patients evaluated, 2,857 (18.8%) received adjuvant systemic therapy. Risk factors for decreased overall survival included age >75 (hazard ratio 3.3, P < .001), male sex (hazard ratio 1.2, P < .001), White/Black race (hazard ratio 1.4, P = .020), preoperative carcinoembryonic antigen >3.5 ng/mL (hazard ratio 1.6, P < .001), T4a T-stage (hazard ratio 2.0, P < .001), T4b T-stage (hazard ratio 2.4, P < .001), lymphovascular invasion (hazard ratio 1.2, P = .003), perineural invasion (hazard ratio 1.3, P = .003), and non-R0 proximal/distal resection margins (hazard ratio 1.7, P < .001). An internally validated risk-score model using these factors was developed composed of low-risk (n = 8,489), moderate-risk (n = 4,623), and high-risk (n = 2,129) groups; within each group, 19.9%, 15.7%, and 20.8% of patients, respectively, received adjuvant systemic therapy. After propensity matching, adjuvant systemic therapy was not associated with improved 5-year overall survival for low-risk patients (89.8% vs 88.3%, P = .280), but was for moderate-risk (80.5% vs 70.8%, P < .001), and high-risk (65.2% vs 45.7%, P < .001) patients. CONCLUSION: A predictive risk-score model incorporating patient and tumor factors identifies a high-risk cohort of stage II colon cancer patients who may benefit from adjuvant systemic therapy, although the minority of these patients appear to be receiving treatment.


Assuntos
Neoplasias do Colo , Quimioterapia Adjuvante , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Neoplasias do Colo/cirurgia , Humanos , Masculino , Estadiamento de Neoplasias , Seleção de Pacientes , Estudos Retrospectivos , Fatores de Risco
4.
JCO Precis Oncol ; 6: e2200060, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35939771

RESUMO

PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) is associated with a poor prognosis. Multianalyte signatures, including liquid biopsy and traditional clinical variables, have shown promise for improving prognostication in other solid tumors but have not yet been rigorously assessed for PDAC. MATERIALS AND METHODS: We performed a prospective cohort study of patients with newly diagnosed locally advanced pancreatic cancer (LAPC) or metastatic PDAC (mPDAC) who were planned to undergo systemic therapy. We collected peripheral blood before systemic therapy and assessed circulating tumor cells (CTCs), cell-free DNA concentration (cfDNA), and circulating tumor KRAS (ctKRAS)-variant allele fraction (VAF). Association of variables with overall survival (OS) was assessed in univariate and multivariate survival analysis, and comparisons were made between models containing liquid biopsy variables combined with traditional clinical prognostic variables versus models containing traditional clinical prognostic variables alone. RESULTS: One hundred four patients, 40 with LAPC and 64 with mPDAC, were enrolled. CTCs, cfDNA concentration, and ctKRAS VAF were all significantly higher in patients with mPDAC than patients with LAPC. ctKRAS VAF (cube root; 0.05 unit increments; hazard ratio, 1.11; 95% CI, 1.03 to 1.21; P = .01), and CTCs ≥ 1/mL (hazard ratio, 2.22; 95% CI, 1.34 to 3.69; P = .002) were significantly associated with worse OS in multivariate analysis while cfDNA concentration was not. A model selected by backward selection containing traditional clinical variables plus liquid biopsy variables had better discrimination of OS compared with a model containing traditional clinical variables alone (optimism-corrected Harrell's C-statistic 0.725 v 0.681). CONCLUSION: A multianalyte prognostic signature containing CTCs, ctKRAS, and cfDNA concentration outperformed a model containing traditional clinical variables alone suggesting that CTCs, ctKRAS, and cfDNA provide prognostic information complementary to traditional clinical variables in advanced PDAC.


Assuntos
Adenocarcinoma , Carcinoma Ductal Pancreático , Ácidos Nucleicos Livres , DNA Tumoral Circulante , Células Neoplásicas Circulantes , Neoplasias Pancreáticas , Adenocarcinoma/genética , Biomarcadores Tumorais/genética , Carcinoma Ductal Pancreático/genética , Ácidos Nucleicos Livres/genética , DNA Tumoral Circulante/genética , Humanos , Células Neoplásicas Circulantes/patologia , Neoplasias Pancreáticas/diagnóstico , Prognóstico , Estudos Prospectivos , Neoplasias Pancreáticas
5.
Case Rep Oncol ; 14(2): 849-853, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34248549

RESUMO

Immunotherapy (IO) has increasingly been demonstrated to provide therapeutic benefit to patients with metastatic colorectal cancer (mCRC). However, only a subset of mCRC tumors respond to IO. Monitoring response with tumor biomarkers like carcinoembryonic antigen (CEA) has been challenging in patients with microsatellite stable (MSS) mCRC due to low expression of CEA (CEA/lo). Noninvasive blood-based biomarkers such as circulating tumor DNA (ctDNA) can inform early treatment response and augment radiographic monitoring. We describe a case study of a patient with chemotherapy-refractory CEA/lo MSS mCRC, with metastatic disease present in a cardiophrenic lymph node. The patient was given 2 cycles of combination IO (ipilimumab/nivolumab). Response was monitored by ctDNA using a multiplex PCR next-generation sequencing assay, CEA, and CT scan. After IO administration, ctDNA levels rapidly declined, becoming undetectable. This was concurrent with radiographic resolution of the lymph node metastasis. Serial monitoring of CEA during this same period was uninformative, with no significant changes observed. Significant decline in ctDNA identified metastatic response to IO in a patient with CEA/lo, MSS mCRC and was concurrently validated by CT scan. This case study provides evidence that ctDNA can be used as a prospective surrogate for radiographic tumor response.

6.
J Clin Oncol ; 38(5): 472-479, 2020 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-31815582

RESUMO

PURPOSE: Platinum-based therapy is the standard of care in patients who have HER2-negative, advanced esophagogastric cancer (AEGC). Retrospective data suggest that intratumoral ERCC1 levels may determine platinum sensitivity. A randomized, phase II study was performed in patients with AEGC to explore whether the efficacy of a platinum-based therapy with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) versus a non-platinum-containing regimen of irinotecan and docetaxel (IT) differed according to ERCC1 levels. PATIENTS AND METHODS: Overall, 202 untreated patients with HER2-negative AEGC and a Zubrod performance status of 0-1 were evaluated prospectively for mRNA expression of ERCC1 level and then randomly assigned to FOLFOX or IT, stratified by the intratumoral statuses of ERCC1 low (< 1.7) or high (≥ 1.7). Objectives were to assess progression-free survival (PFS) and overall survival (OS) in all patients treated with FOLFOX compared with IT, stratified by low and high ERCC1 levels, and to assess for interactive effects between ERCC1 expression and treatment arm. RESULTS: Eighty-six percent of patients had ERCC1 values < 1.7. Thus, evaluation of the ERCC1-high subgroup was limited. Grade ≥ 3 anemia, dehydration, diarrhea, and fatigue were greater in patients with IT. Occurrences of grade ≥ 3 neuropathy and decreased neutrophils were greater in patients with FOLFOX. In all patients, FOLFOX had a statistically superior median PFS compared with IT (5.7 v 2.9 months; hazard ratio, 0.68; P = .02). In patients with ERCC1 levels < 1.7 receiving FOLFOX, PFS and response rate were statistically superior to IT, with no significant difference in OS. CONCLUSION: The evaluation of ERCC1 in patients with upper GI tumors was thwarted by an overwhelming predominance of low ERCC1 mRNA expression. Nonetheless, distribution of treatment effects on PFS did not vary with expression. For all patients and for those with low ERCC1 expression, FOLFOX was superior in efficacy to IT.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Proteínas de Ligação a DNA/genética , Endonucleases/genética , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/genética , Junção Esofagogástrica/patologia , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Proteínas de Ligação a DNA/biossíntese , Endonucleases/biossíntese , Neoplasias Esofágicas/patologia , Junção Esofagogástrica/efeitos dos fármacos , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Expressão Gênica , Humanos , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Oxaliplatina/administração & dosagem , Oxaliplatina/efeitos adversos , Prognóstico , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Estudos Prospectivos , Neoplasias Gástricas/patologia , Adulto Jovem
7.
Oncologist ; 14(2): 119-24, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19182243

RESUMO

PURPOSE: To determine the optimal dose of the antiepidermal growth factor receptor (EGFR) monoclonal antibody cetuximab that can be safely administered in combination with a standard daily dose of erlotinib in patients with advanced solid malignancies. PATIENTS AND METHODS: Patients with advanced solid malignancies who had failed standard chemotherapies received escalating doses of cetuximab without a loading dose (100, 200, 250 mg/m(2) i.v. weekly) in combination with a fixed dose of erlotinib (150 mg daily orally) until disease progression or unacceptable toxicity. RESULTS: Twenty-two patients were treated, including 14 patients (64%) with non-small cell lung cancer. Twenty patients received combination treatment at the highest dose level for a median of 5.5 weeks (range, 1-31 weeks). One dose-limiting toxicity was observed: grade 3 skin rash. Overall, the most common adverse events (any grade, grade 3/4) were consistent with the safety profiles of the individual drugs: acneform rash (100%, 9%), diarrhea (77%, 5%), and hypomagnesemia (59%, 12%). Seven of 18 evaluable patients (38.9%) had stable disease lasting for a median of 16.6 weeks (range, 6.1-25.1 weeks). CONCLUSION: Dual EGFR inhibition with cetuximab and erlotinib is feasible; the observed toxicities were manageable and consistent with the safety profiles of the individual drugs. The recommended doses for phase II studies are 250 mg/m(2) i.v. weekly for cetuximab and 150 mg daily orally for erlotinib.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Receptores ErbB/antagonistas & inibidores , Neoplasias/tratamento farmacológico , Adulto , Idoso , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cetuximab , Relação Dose-Resposta a Droga , Receptores ErbB/metabolismo , Cloridrato de Erlotinib , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/enzimologia , Neoplasias/patologia , Quinazolinas/administração & dosagem , Quinazolinas/efeitos adversos
8.
Invest New Drugs ; 27(6): 565-70, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19214387

RESUMO

PURPOSE: Enzastaurin is a potent, serine-threonine kinase inhibitor which selectively targets PKCß and PI3K/AKT signaling pathways to reduce cell proliferation, induce apoptosis, and inhibit angiogenesis. As PKCbeta and PI3K/AKT signaling are both involved in breast cancer pathogenesis, this phase II study evaluated the efficacy and toxicity of enzastaurin in previously treated patients with metastatic breast cancer (MBC). PATIENTS AND METHODS: Eligible patients had histologically confirmed MBC with measurable disease, and must have received prior anthracycline and taxane chemotherapy, but not more than two prior regimens for MBC. Human epidermal growth factor 2 (HER2)-positive patients must have progressed on prior trastuzumab therapy. Enzastaurin, 1,125-mg loading dose on day 1 followed by 500 mg daily, was administered orally in 28-day cycles. Response was assessed every 2 cycles according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. RESULTS: Twenty-one patients enrolled between November 2006 and September 2007. Fourteen (66.7%) patients completed at least two cycles of therapy. No patients developed Grade 3/4 hematologic toxicity. Grade 3 nonhematologic toxicity was rare (<5%) and most commonly attributed to MBC progression. There were no objective responses and no patients with stable disease for >/=6 months. Median progression-free survival was 1.68 months (95%CI: 1.02, 1.74). CONCLUSIONS: Enzastaurin monotherapy was well tolerated, but demonstrated no activity in patients with heavily pretreated MBC.


Assuntos
Antraciclinas/uso terapêutico , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Hidrocarbonetos Aromáticos com Pontes/uso terapêutico , Indóis/administração & dosagem , Indóis/uso terapêutico , Taxoides/uso terapêutico , Administração Oral , Adulto , Idoso , Neoplasias da Mama/patologia , Feminino , Humanos , Indóis/efeitos adversos , Pessoa de Meia-Idade , Metástase Neoplásica , Resultado do Tratamento
9.
J Clin Oncol ; 37(34): 3266-3274, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31618129

RESUMO

PURPOSE: We evaluated the addition of bevacizumab, a humanized monoclonal antibody that targets vascular endothelial growth factor, to platinum-based chemotherapy in recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: Patients with chemotherapy-naïve (or with prior platinum as part of multimodal therapy completed ≥ 4 months earlier) recurrent or metastatic SCCHN were randomly assigned to receive a platinum-based chemotherapy doublet with or without bevacizumab 15 mg/kg given intravenously every 3 weeks until disease progression. Chemotherapy could be discontinued after six cycles if a maximum response was achieved. RESULTS: The study randomly assigned 403 patients. Median overall survival (OS) was 12.6 months with bevacizumab plus chemotherapy (BC) and 11.0 months with chemotherapy alone (hazard ratio, 0.87; 95% CI, 0.70 to 1.09; P = .22). At 2, 3, and 4 years, the OS rates were 25.2% v 18.1%, 16.4% v 10.0%, and 11.8% v 6.4% for BC versus chemotherapy, respectively. In an analysis of 365 eligible patients who started treatment, the hazard ratio was 0.82 (95% CI, 0.65 to 1.04; P = .10), with a median OS of 14.2 months on BC v 11.1 months on chemotherapy. Median progression-free survival with BC was 6.0 months v 4.3 months with chemotherapy (P = .0014). Overall response rates were 35.5% with BC and 24.5% with chemotherapy (P = .016). There was increased toxicity, including a higher rate of treatment-related grade 3 to 5 bleeding events (6.7% v 0.5%; P < .001) and treatment-related deaths (9.3% v 3.5%; P = .022) with BC versus chemotherapy. CONCLUSION: The addition of bevacizumab to chemotherapy did not improve OS but improved the response rate and progression-free survival with increased toxicities. These results encourage biomarker-driven studies of angiogenesis inhibitors with better toxicity profiles in select patients with SCCHN.


Assuntos
Antineoplásicos Imunológicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bevacizumab/administração & dosagem , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Recidiva Local de Neoplasia , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Idoso , Antineoplásicos Imunológicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/efeitos adversos , Progressão da Doença , Esquema de Medicação , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Intervalo Livre de Progressão , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/secundário , Fatores de Tempo , Estados Unidos
10.
Mol Cancer Res ; 5(6): 585-603, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17579118

RESUMO

A dynamic interplay between prostate cancer cells and reactive bone stroma modulates growth of metastases within bone. We used microarray analysis to screen for changes in gene expression in bone marrow stromal cells cocultured with prostate cancer cells and found reduced expression of endoglin, a transmembrane glycoprotein that functions as an auxiliary coreceptor for members of the transforming growth factor beta (TGF-beta) family of cytokines. The downstream TGF-beta/bone morphogenetic protein signaling pathway including Smad1 and Smad2/3 also was attenuated, as was Smad-dependent gene transcription. Smad1/5/8-dependent inhibitor of DNA binding 1 expression and Smad2/3-dependent plasminogen activator inhibitor I expression both were decreased and were accompanied by decreased cell proliferation. Small interfering RNA-mediated knockdown of endoglin in HS-5 cells verified that the effects on signaling were a direct result of the attenuation of endoglin. These data illustrate that endoglin acts as a positive regulator of both activin receptor-like kinase 1-induced Smad1/5/8 activation and activin receptor-like kinase 5-induced Smad2/3 activation in bone marrow stromal cells. In addition, the data illustrate that one early event of metastasis upon the arrival of prostate cancer cells into the bone stroma is attenuated endoglin expression in the stromal cells, which subsequently alters Smad signaling and cell proliferation. We hypothesize that coculture of bone marrow stromal cells with prostate cancer cells alters TGF-beta signaling in the stromal cells, ultimately facilitating growth of the cancer cells in the bone compartment. Collectively, these studies suggest that prostate cancer cells modulate TGF-beta responsiveness of bone marrow stroma as one means of facilitating their own growth in bone.


Assuntos
Células da Medula Óssea/citologia , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Células Estromais/citologia , Fator de Crescimento Transformador beta/metabolismo , Antígenos CD/metabolismo , Apoptose , Osso e Ossos/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Técnicas de Cocultura , Meios de Cultivo Condicionados/farmacologia , Endoglina , Humanos , Masculino , Metástase Neoplásica , Receptores de Superfície Celular/metabolismo , Transdução de Sinais
11.
Surg Oncol Clin N Am ; 17(1): 197-218, x, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18177807

RESUMO

Survival from differentiated thyroid carcinoma is generally good, but postoperative management plays an important role in minimizing the likelihood of disease recurrence. Postoperative management is generally performed by endocrinologists and nuclear medicine physicians, who exploit thyroid cells' inherent iodineavidity and sensitivity to hormonal manipulation in a unique cancer management paradigm. Endocrinologists manage thyroid hormone replacement/thyroid stimulating hormone suppression and coordinate surveillance. Nuclear physicians administer targeted therapy with radioactive iodine and perform imaging studies to assess disease status. This article provides an overview of the postoperative assessment, treatment, and follow-up of patients who have thyroid carcinoma.


Assuntos
Cuidados Pós-Operatórios , Neoplasias da Glândula Tireoide/cirurgia , Humanos , Compostos de Iodo , Recidiva Local de Neoplasia , Radioisótopos , Radioterapia , Medição de Risco , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/patologia
12.
Oral Oncol ; 78: 102-107, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29496036

RESUMO

OBJECTIVES: The objective of this study was to investigate the safety, tolerability and preliminary efficacy of radiotherapy plus cetuximab in high risk CSCC patients. MATERIALS AND METHODS: Patients with high-risk CSCC diagnosed between 2006 and 2013 were analyzed. Patients were divided into two groups: radiotherapy alone versus radiotherapy plus cetuximab. Among 68 patients meeting study criteria, we identified 29 treated with cetuximab plus RT and 39 with RT alone. Primary analysis examined disease-free and overall survival, freedom from local and distant recurrence in the propensity score matched cohort. Propensity score analysis was performed with weighted factors including: Charlson Comorbidity Index score, age. KPS, primary location, T and N stage, recurrent status, margin status, LVSI, PNI and grade. Toxicity was assessed using the CTCAE v4.0. RESULTS: Median follow-up for living patients was 30 months. Patients in the cetuximab group were more likely to have advanced N stage, positive margins and recurrent disease. After propensity score matching the groups were well balanced. Six patients experienced ≥ grade 3 acute toxicity in the cetuximab group. The 1-year, 2-year and 5-year progression free survival (PFS) for patients in the cetuximab group were 86%, 72% and 66%, respectively. The 1-year, 2-year and 5-year overall survival (OS) for patients in the cetuximab group was 98%, 80% and 80%, respectively. CONCLUSIONS: Although limited by small numbers, the combination of cetuximab and radiotherapy in CSCC appears well tolerated there were more long-term survivors and less distant metastasis in the cetuximab group. These promising finding warrant further studies.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Cetuximab/uso terapêutico , Quimiorradioterapia , Neoplasias Cutâneas/terapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Cuidados Pós-Operatórios , Análise de Sobrevida
13.
Cancer Med ; 7(7): 2969-2973, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29905018

RESUMO

Lung cancer remains the leading cause of cancer death throughout the world. Despite new chemotherapeutic, immunomodulating and molecularly targeted agents, patients with locally advanced or metastatic disease still have a poor prognosis. This trial looked to combine antiangiogenic therapy with a first-line cytotoxic chemotherapy doublet, hoping to extend median progression-free survival (PFS) while minimizing toxicity in patients with advanced nonsquamous non-small-cell lung cancer (NSCLC). In this single institution, single-arm study, 51 patients (age >18 yo) were followed from 2007 to 2012. Patients with stage IV nonsquamous NSCLC and patients with recurrent unresectable disease (nonradiation candidates) were eligible. Treatment consisted of carboplatin AUC 5 IV 30-60 minutes, pemetrexed 500/mg2 IV 10 minutes, bevacizumab 15 mg/kg IV (90 minutes 1st dose, 60 minutes 2nd dose, 30 minutes subsequent doses). Treatment was administered every 21 days and planned for 6 cycles, in the absence of disease progression or unacceptable toxicities. Growth factor support was not permitted prophylactically but allowed for toxicities, as were dose reductions. Maintenance treatment for those with stable disease or better consisted of Bevacizumab 15 mg/kg every 3 weeks for up to 1 year. Between November 2007 and March 2012, 51 patients were followed in the phase II trial of carboplatin, pemetrexed, and bevacizumab. Patients were enrolled over a 24-month period. After the end of treatment visits, subjects were followed at least every 3 months for survival data. The median follow-up period was 49 weeks (6 weeks to 178), and the median number of treatment cycles was 6 (range, 1-6). Among the 50 patients assessable for response, median overall survival was 49 weeks (95% CI, 0-62.7) with median PFS of 28 weeks (95% CI, 0-132.4). A complete or partial response was seen in 28 (59.5%) patients. Grade 3-4 treatment-related adverse events occurred in 9 (17.6%) of 51 patients; the most common were thrombocytopenia (4 [7.8%]) and neutropenia (3 [5.9%]). Three (5.8%) of 51 patients were discontinued because of treatment-related adverse events (grade 3 diarrhea, thrombocytopenia, dehydration, fatigue, and grade 4 respiratory distress), and 1 patient (1.9%) was found to be ineligible due to anticoagulation use. A novel 3-drug combination for advanced nonsquamous NSCLC shows promising efficacy with modest toxicity.

14.
JAMA Oncol ; 4(11): 1583-1588, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-29931076

RESUMO

Importance: Immunotherapy for recurrent and/or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN) is promising. The toll-like receptor 8 (TLR8) agonist motolimod may stimulate innate and adaptive immunity. Objective: To determine whether motolimod improves outcomes for R/M SCCHN when combined with standard therapy. Design, Setting, and Participants: The Active8 study was a multicenter, randomized, double-blind, placebo-controlled clinical trial enrolling adult patients (age ≥18 years) with histologically confirmed R/M SCCHN of the oral cavity, oropharynx, hypopharynx, or larynx between October 2013 and August 2015. Follow-up ended September 2016. Analysis for the present report was conducted between June 2016 and December 2017. Interventions: Combination treatment with platinum (carboplatin or cisplatin), fluorouracil, cetuximab (the EXTREME regimen), and either placebo or motolimod, each administered intravenously every 3 weeks. Patients received a maximum of 6 chemotherapy cycles, after which patients received weekly cetuximab with either placebo or motolimod every 4 weeks. Main Outcomes and Measures: Progression-free survival (PFS) as determined by independent central review using immune-related RECIST (Response Evaluation Criteria in Solid Tumors). Key secondary end points included overall survival (OS) and safety. Results: Of 195 patients enrolled, 85% were men (n = 166); 82% were white (n = 159); median age was 58 years (range 23-81 years). Median PFS was 6.1 vs 5.9 months (hazard ratio [HR], 0.99; 1-sided 90% CI, 0.00-1.22; P = .47), and median OS was 13.5 vs 11.3 months (HR, 0.95; 1-sided 90% CI, 0.00-1.22; P = .40) for motolimod vs placebo. Increased incidence of injection site reactions, pyrexia, chills, anemia, and acneiform rash were noted with motolimod. Of 83 cases oropharyngeal cancer, 52 (63%) were human papillomavirus (HPV) positive. In a prespecified subgroup analysis of HPV-positive participants, motolimod vs placebo resulted in significantly longer PFS (7.8 vs 5.9 months; HR, 0.58; 1-sided 90% CI, 0.00-0.90; P = .046) and OS (15.2 vs 12.6 months; HR, 0.41; 1-sided 90% CI, 0.00-0.77; P = .03). In an exploratory analysis, patients with injection site reactions had longer PFS and OS (median PFS, 7.1 vs 5.9 months; HR, 0.69; 1-sided 90% CI, 0.00-0.93; P = .06; and median OS, 18.7 vs 12.6; HR, 0.56; 1-sided 90% CI, 0.00-0.81; P = .02). Conclusions and Relevance: Adding motolimod to the EXTREME regimen was well tolerated but did not improve PFS or OS in the intent-to-treat population. Significant benefit was observed in HPV-positive patients and those with injection site reactions, suggesting that TLR8 stimulation may benefit subset- and biomarker-selected patients. Trial Registration: ClinicalTrials.gov identifier: NCT01836029.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Benzazepinas/uso terapêutico , Cetuximab/uso terapêutico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/farmacologia , Benzazepinas/farmacologia , Cetuximab/farmacologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Adulto Jovem
15.
Clin Cancer Res ; 23(19): 5711-5719, 2017 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-28679770

RESUMO

Purpose: We evaluated a Trop-2-targeting antibody conjugated with SN-38 in metastatic small cell lung cancer (mSCLC) patients.Experimental Design: Sacituzumab govitecan was studied in patients with pretreated (median, 2; range, 1-7) mSCLC who received either 8 or 10 mg/kg i.v. on days 1 and 8 of 21-day cycles. The primary endpoints were safety and objective response rate (ORR); duration of response, progression-free survival (PFS), and overall survival (OS) were secondary endpoints.Results: Sixty percent of patients showed tumor shrinkage from baseline CTs. On an intention-to-treat basis (N = 50), the ORR was 14% (17% for the 10-mg/kg group); the median response duration, 5.7 months; the clinical benefit rate (CBR ≥4 months), 34%; median PFS, 3.7 months; and median OS, 7.5 months. There was a suggested improvement in PR, CBR, and PFS with sacituzumab govitecan in second-line patients who were sensitive to first-line therapy, but no difference between first-line chemosensitive versus chemoresistant patients in the overall population. There was a statistically significant higher OS in those patients who received prior topotecan versus no topotecan therapy in a small subgroup. Grade ≥3 adverse events included neutropenia (34%), fatigue (13%), diarrhea (9%), and anemia (6%). Trop-2 tumor staining was not required for patient selection. No antibodies to the drug conjugate or its components were detected on serial blood collections.Conclusions: Sacituzumab govitecan appears to have a safe and effective therapeutic profile in heavily pretreated mSCLC patients, including those who are chemosensitive or chemoresistant to first-line chemotherapy. Additional studies as a monotherapy or combination therapy are warranted. Clin Cancer Res; 23(19); 5711-9. ©2017 AACR.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Antígenos de Neoplasias/imunologia , Camptotecina/análogos & derivados , Camptotecina/administração & dosagem , Moléculas de Adesão Celular/imunologia , Imunoconjugados/administração & dosagem , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/efeitos adversos , Camptotecina/efeitos adversos , Camptotecina/imunologia , Moléculas de Adesão Celular/antagonistas & inibidores , DNA Topoisomerases Tipo I/genética , DNA Topoisomerases Tipo I/imunologia , Intervalo Livre de Doença , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/classificação , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Humanos , Imunoconjugados/efeitos adversos , Imunoconjugados/química , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Carcinoma de Pequenas Células do Pulmão/imunologia , Carcinoma de Pequenas Células do Pulmão/patologia , Inibidores da Topoisomerase I/administração & dosagem , Inibidores da Topoisomerase I/efeitos adversos
16.
Oral Oncol ; 51(6): 616-21, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25868716

RESUMO

PURPOSE: To update the outcomes of an institutional clinical management approach using ipsilateral neck radiotherapy in the treatment of node-positive squamous cell carcinoma of the tonsil with a well-lateralized primary lesion. METHODS AND MATERIALS: Between August 2003 and April 2014, 61 consecutive patients with ipsilateral node-positive squamous cell carcinoma of the tonsil without involvement of the base of the tongue or midline soft palate were treated at a community hospital-based cancer center with radiotherapy to the primary site and ipsilateral neck. Overall survival, disease-free survival and freedom from contralateral failure were calculated. RESULTS: Median follow up was 37.2months (range 4-121months). Freedom from contralateral nodal failure at 5years was 98% with one contralateral nodal failure noted. The patient underwent a salvage neck dissection and was treated with post-operative radiotherapy with no evidence of disease to date. 5-year overall survival (OS) was 92.4% and 5year disease-free survival (DFS) was 86.7%. CONCLUSIONS: This represents the single largest series reported from a community hospital-based cancer center in which lateralized tonsil cancers with N+ disease were treated with ipsilateral neck radiotherapy. In this carefully selected cohort of patients with well-lateralized tonsil cancers, the risk of contralateral nodal failure appears to be <5%, suggesting that prophylactic radiation of the contralateral neck may not be necessary. Future planned studies will focus on prospectively selecting subgroups of patients eligible for treatment de-intensification as survivorship issues in excellent prognosis HPV positive patients are increasingly becoming relevant.


Assuntos
Carcinoma de Células Escamosas/radioterapia , Terapia Combinada/métodos , Neoplasias Tonsilares/radioterapia , Adulto , Idoso , Carcinoma de Células Escamosas/cirurgia , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esvaziamento Cervical/métodos , Prognóstico , Estudos Retrospectivos , Neoplasias Tonsilares/cirurgia
17.
J Clin Oncol ; 32(22): 2311-7, 2014 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-24934787

RESUMO

PURPOSE: Optimal adjuvant chemotherapy for early-stage breast cancer balances efficacy and toxicity. We sought to determine whether single-agent paclitaxel (T) was inferior to doxorubicin and cyclophosphamide (AC), when each was administered for four or six cycles of therapy, and whether it offered less toxicity. PATIENTS AND METHODS: Patients with operable breast cancer with 0 to 3 positive nodes were enrolled onto the study to address the noninferiority of single-agent T to AC, defined as the one-sided 95% upper-bound CI (UCB) of hazard ratio (HR) of T versus AC less than 1.30 for the primary end point of relapse-free survival (RFS). As a 2 × 2 factorial design, duration of therapy was also addressed and was previously reported. RESULTS: With 3,871 patients enrolled onto the trial, a median follow-up period of 6.1 years, and 437 RFS events, we achieved an HR of 1.26 (one sided 95% UCB, 1.48; favoring AC does not allow a conclusion of noninferiority of T with AC; UCB > 1.3). With 266 patient deaths, the HR for overall survival (OS) was 1.27 favoring AC (UCB, 1.56). The estimated absolute advantage of AC at 5 years is 3% for RFS (91 v 88%) and 1% for OS (95 v 94%). All nine treatment-related deaths were patients receiving AC and are included in the analyses of both RFS and OS. Hematologic toxicity was more common in patients treated with AC, and neuropathy was more common in patients treated with T. CONCLUSION: This trial did not show noninferiority of T to AC, a conclusion that is unlikely to change with additional events and follow-up. T was less toxic than AC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Paclitaxel/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Paclitaxel/efeitos adversos , Resultado do Tratamento
18.
J Clin Oncol ; 30(33): 4071-6, 2012 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-22826271

RESUMO

PURPOSE: The ideal duration of adjuvant chemotherapy for patients with lower risk primary breast cancer is not known. Cancer and Leukemia Group B trial 40101 was conducted using a phase III factorial design to define whether six cycles of a chemotherapy regimen are superior to four cycles. We also sought to determine whether paclitaxel (T) is as efficacious as doxorubicin/cyclophosphamide (AC), but with reduced toxicity. PATIENTS AND METHODS: Between 2002 and 2008, the study enrolled women with operable breast cancer and zero to three positive nodes. Patients were randomly assigned to either four or six cycles of either AC or T. Study stratifiers were estrogen receptor/progesterone receptor (ER/PgR), human epidermal growth factor receptor 2 (HER2), and menopausal status. After 2003, all treatment was administered in dose-dense fashion. The primary efficacy end point was relapse-free survival (RFS). RESULTS: A total of 3,171 patients were enrolled; 94% were node-negative and 6% had one to three positive nodes. At a median follow-up of 5.3 years, the 4-year RFS was 90.9% and 91.8% for six and four cycles, respectively. The adjusted hazard ratio (HR) of six to four cycles regarding RFS was 1.03 (95% CI, 0.84 to 1.28; P=.77). The 4-year OS was 95.3% and 96.3% for six and four cycles, respectively, with an HR of six to four cycles of 1.12 (95% CI, 0.84 to 1.49; P=.44). There was no interaction between treatment duration and chemotherapy regimen, ER/PgR, or HER2 status on RFS or OS. CONCLUSION: For women with resected primary breast cancer and zero to three positive nodes, we found no evidence that extending chemotherapy regimens of AC or single-agent T from four to six cycles improves clinical outcome.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Esquema de Medicação , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Fatores de Risco
19.
J Clin Oncol ; 29(20): 2808-14, 2011 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-21670453

RESUMO

PURPOSE: Oral mucositis (OM) is a debilitating toxicity of chemoradiotherapy for head and neck cancer (HNC). This randomized, placebo-controlled, double-blind study evaluated the efficacy and safety of palifermin to reduce OM associated with definitive chemoradiotherapy for locally advanced HNC. PATIENTS AND METHODS: Patients receiving conventionally fractionated radiotherapy (2.0 Gy/d, 5 days/wk to 70 Gy) with cisplatin (100 mg/m(2) on days 1, 22, and 43) received palifermin (180 µg/kg) or placebo before starting chemoradiotherapy and then once weekly for 7 weeks. The primary end point was the incidence of severe, observable, and functional OM (WHO grade 3 to 4). RESULTS: The palifermin (n = 94) and placebo (n = 94) arms were well balanced. The incidence of severe OM was significantly lower for palifermin than for placebo (54% v 69%; P = .041). In the palifermin arm, median time to severe OM was delayed (47 v 35 days), median duration of severe OM was shortened (5 v 26 days), and the incidence of xerostomia grade ≥ 2 was lower (67% v 80%), favoring palifermin; however, the differences were not significant after multiplicity adjustment. Opioid analgesic use, average mouth and throat soreness scores, and chemoradiotherapy compliance were not significantly different between treatment arms. Adverse events were similar between arms (98%, palifermin; 93%, placebo). The most common study drug-related adverse events were rash, flushing, and dysgeusia. After median follow-up of 25.8 months, overall survival and progression-free survival were similar between treatment arms. CONCLUSION: Although palifermin reduced severe functional OM, its role in the management of locally advanced HNC during chemoradiotherapy remains to be elucidated.


Assuntos
Fator 7 de Crescimento de Fibroblastos/uso terapêutico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Estomatite/prevenção & controle , Antineoplásicos/efeitos adversos , Cisplatino/efeitos adversos , Terapia Combinada/efeitos adversos , Método Duplo-Cego , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Fator 7 de Crescimento de Fibroblastos/efeitos adversos , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Estomatite/etiologia , Análise de Sobrevida
20.
Oncologist ; 7(6): 509-15, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12490738

RESUMO

PURPOSE: To determine the optimal dose of combination topotecan, cisplatin, and gemcitabine in advanced non-small cell lung cancer patients. MATERIALS AND METHODS: This single-center, single-practice, phase I trial enrolled chemotherapy-naïve patients with inoperable stage IIIB/IV disease. Initial treatment was topotecan (0.5-2.0 mg/m(2)), cisplatin (20 mg/m(2)), and gemcitabine (1,000 mg/m(2)) on days 1, 8, and 15 of a 28-day cycle. Dose-limiting thrombocytopenia at week 3 necessitated less frequent gemcitabine dosing (days 1 and 15 of each cycle). Thereafter, topotecan dose escalation proceeded to the target dose of 2 mg/m(2). RESULTS: Thirty patients were enrolled and evaluable for toxicity assessment. Treatment was extremely well tolerated: only one grade 4 adverse event (leukopenia); no hospitalizations for treatment-related toxicities; no fever/neutropenia. Although no dose-limiting toxicities developed, 1.75 mg/m(2) topotecan is considered optimal and recommended for further study because it was well tolerated, active, and did not require dose adjustments or delays in therapy. Eleven of 29 (38%) evaluable patients achieved a partial response. Median survival was 38 weeks (range 4-110 weeks), median progression-free survival was 17 weeks, and the 1-year survival rate was 33%. Two patients remain alive after 108-122 weeks of follow-up. CONCLUSION: A 28-day cycle of topotecan (1.75 mg/m(2) days 1, 8, 15), cisplatin (20 mg/m(2) days 1, 8, 15), and gemcitabine (1,000 mg/m(2) days 1, 15) was a safe and well-tolerated outpatient treatment for advanced non-small cell lung cancer. The favorable preliminary efficacy and safety of this regimen suggest that further study in phase II trials, including quality-of-life end points, is warranted.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Desoxicitidina/análogos & derivados , Neoplasias Pulmonares/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Cisplatino/administração & dosagem , Desoxicitidina/administração & dosagem , Progressão da Doença , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Análise de Sobrevida , Trombocitopenia/induzido quimicamente , Topotecan/administração & dosagem , Resultado do Tratamento , Gencitabina
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