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1.
Cancer ; 127(17): 3060-3063, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-33957707

RESUMO

LAY SUMMARY: Although smoking has traditionally been the dominant causative factor of head and neck cancer, cancers of the tonsils and base of tongue increasingly are being driven by human papillomavirus, and these cancers are easier to cure. When radiation is used as the primary curative treatment, a number of studies have shown good outcomes with reduced doses of both radiation and chemotherapy. New techniques that access the tumor through the mouth instead of the jaw have made surgery dramatically less toxic. Outcomes are favorable, and many patients traditionally given radiation and chemotherapy afterward may be able to safely omit them.


Assuntos
Alphapapillomavirus , Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Orofaríngeas , Procedimentos Cirúrgicos Robóticos , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Neoplasias de Cabeça e Pescoço/etiologia , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Neoplasias Orofaríngeas/virologia , Papillomaviridae , Procedimentos Cirúrgicos Robóticos/efeitos adversos
2.
Cancer ; 127(23): 4447-4454, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34379792

RESUMO

BACKGROUND: Adavosertib (AZD1775) is an inhibitor of the Wee1 kinase. The authors conducted a phase 1b trial to evaluate the safety of adavosertib in combination with definitive chemoradiotherapy for patients with newly diagnosed, intermediate-risk/high-risk, locally advanced head and neck squamous cell carcinoma (HNSCC). METHODS: Twelve patients with intermediate-risk/high-risk HNSCC were enrolled, including those with p16-negative tumors of the oropharynx, p16-positive tumors of the oropharynx with ≥10 tobacco pack-years, and tumors of the larynx/hypopharynx regardless of p16 status. All patients were treated with an 8-week course of concurrent intensity-modulated radiotherapy at 70 grays (Gy) (2 Gy daily in weeks 1-7), cisplatin 30 mg/m2 weekly (in weeks 1-7), and adavosertib (twice daily on Monday, Tuesday, and Wednesday of weeks 1, 2, 4, 5, 7, and 8). The primary objective was to determine the maximum tolerated dose and the recommended phase 2 dose of adavosertib given concurrently with radiation and cisplatin. Secondary objectives were to determine the 12-week objective response rate and progression-free and overall survival. RESULTS: Three patients (25%) experienced a dose-limiting toxicity, including febrile neutropenia (n = 2) and grade 4 thromboembolism (n = 1). Two dose-limiting toxicities occurred with adavosertib at 150 mg. The median follow-up was 14.7 months. The 12-week posttreatment objective response rate determined by positron emission tomography/computed tomography was 100%. The 1-year progression-free and overall survival rates were both 90%. The maximum tolerated dose of adavosertib was 100 mg. CONCLUSIONS: Adavosertib 100 mg (twice daily on Monday, Tuesday, and Wednesday of weeks 1, 2, 4, 5, 7, and 8), in combination with 70 Gy of intensity-modulated radiotherapy and cisplatin 30 mg/m2 , is the recommended phase 2 dose for patients with HNSCC.


Assuntos
Cisplatino , Neoplasias de Cabeça e Pescoço , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Cisplatino/efeitos adversos , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Pirazóis , Pirimidinonas , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia
3.
Cancer ; 126(5): 1060-1067, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31943168

RESUMO

BACKGROUND: The selection of later-line treatment for older patients with AJCC (version 7) stage IV non-small cell lung cancer (NSCLC) remains controversial. Nanoparticle albumin-bound (nab)-paclitaxel is approved with carboplatin for the first-line treatment of patients with NSCLC and subgroup analysis of phase 3 data has suggested superior survival in older patients. METHODS: The authors conducted a phase 2 study of nab-paclitaxel in 42 patients aged ≥70 years who had been treated previously with a platinum doublet regimen; patients also could have received a PD-1 inhibitor. The primary endpoint of the current study was grade 3 to 5 toxicity (according to the National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0]). In addition to response rate, progression-free survival (PFS), and overall survival (OS), geriatric assessments also were performed before and during treatment, associations between baseline sarcopenia and outcomes were explored, and changes in T lymphocyte p16 before and during treatment were measured. The authors also performed a retrospective subgroup analysis of 19 older patients who were treated with nab-paclitaxel as part of a larger, randomized, phase 2 study; data were not combined. RESULTS: The rate of grade 3 to 5 toxicities was 33.7%. The most common grade 3 to 5 toxicities were decreased white blood cell count (11.9%), neutropenia (9.5%), and fatigue (11.9%). The response rate was 34.2% (2.6% complete response rate and 31.6% partial response rate). The median PFS was 5.2 months and the median OS was 9.3 months. Adverse prognostic factors were common: 42% of patients were frail and 39% of patients were prefrail, whereas 21% had an Eastern Cooperative Oncology Group performance status of 2 and 27% were sarcopenic. Only frailty was found to be predictive of inferior survival. A subgroup analysis of 19 older patients treated with nab-paclitaxel alone in a prior trial demonstrated a response rate of 15.8%, a PFS of 4.2 months, and an OS of 13.6 months. CONCLUSIONS: Fit and prefrail older patients with stage IV NSCLC should be considered for treatment with nab-paclitaxel after disease progression with doublet chemotherapy.


Assuntos
Adenocarcinoma de Pulmão/tratamento farmacológico , Albuminas/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma de Células Escamosas/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Paclitaxel/uso terapêutico , Platina/administração & dosagem , Terapia de Salvação , Adenocarcinoma de Pulmão/patologia , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/patologia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/patologia , Masculino , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
4.
Cancer ; 124(14): 2986-2992, 2018 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-29741773

RESUMO

BACKGROUND: The objective of this study was to demonstrate the feasibility and efficacy of induction chemotherapy, surgery, and pathology-guided adjuvant therapy to treat transorally resectable squamous head and neck cancer. METHODS: Patients had squamous head and neck cancer that was resectable by the transoral route and advanced-stage disease (American Joint Committee on Cancer stage III-IV, T3-T4 tumors, and/or positive lymph nodes). They received treatment with weekly carboplatin at an area under the curve of 2, plus paclitaxel 135 mg/m2 , and daily lapatinib 1000mg for 6 weeks followed by surgical resection. Pathology that revealed margins <5 mm, extracapsular extension, N2a of N2b lymph node status, perineural invasion, or lymphovascular space invasion resulted in adjuvant radiotherapy concurrent with weekly cisplatin. Pathology with N2c/N3 lymph node status or positive margins resulted in radiation with bolus cisplatin. The primary endpoint was the clinical response rate to induction chemotherapy, and a key secondary endpoint was feasibility. RESULTS: Toxicity was modest, and 37 of 40 patients completed study procedures as planned. The clinical response rate was 93%, the pathologic complete response rate was 36%, and the clinical response did not predict for a pathologic complete response. No patient on study follow-up has recurred or died. Twenty-nine of 39 patients who underwent surgery avoided radiation. Speech and swallowing function were well preserved. CONCLUSIONS: The study met both its primary efficacy endpoint and the secondary feasibility endpoint. Neoadjuvant, systemic therapy and surgical resection followed by risk-adapted adjuvant therapy resulted in high response rates and excellent long-term outcomes and should be further studied. Cancer 2018;124:2986-92. © 2018 American Cancer Society.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Endoscopia/métodos , Neoplasias de Cabeça e Pescoço/terapia , Recidiva Local de Neoplasia/prevenção & controle , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Adulto , Idoso , Quimiorradioterapia Adjuvante/métodos , Quimiorradioterapia Adjuvante/estatística & dados numéricos , Estudos de Viabilidade , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Seleção de Pacientes , Intervalo Livre de Progressão , Medição de Risco , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
5.
Cancer ; 122(15): 2350-5, 2016 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-27197056

RESUMO

BACKGROUND: The combination of cisplatin, 5-fluorouracil, and cetuximab is a standard treatment for patients with recurrent/metastatic head and neck cancer, with a high rate of toxicity. Identifying less toxic, equally effective regimens is imperative. Therefore, in the current study, the authors investigated first-line treatment with an all-oral regimen of capecitabine and lapatinib. METHODS: Patients were required to have incurable head and neck cancer of any primary site other than the nasopharynx, an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 2, and no prior exposure to capecitabine or lapatinib. Subjects were treated with capecitabine at a dose of 1000 mg/m(2) twice daily and lapatinib at a dose of 1250 mg daily. Capecitabine was administered for 14 days of each 21-day cycle for 4 cycles. Lapatinib was administered daily until disease progression. The primary outcome was overall survival. RESULTS: A total of 44 subjects were accrued between November 13, 2009 and April 29, 2014. Approximately 38.6% of the sample had an ECOG PS of 0, 52.3% had an ECOG PS of 1, and 9.1% had an ECOG PS of 2. Approximately 81.8% were male and the median age of the patients was 62 years. Prior attempts at curative treatment with chemotherapy had been used in 68.2% of patients (platinum was used in 55.8%). There was no grade 5 toxicity noted (toxicity was graded according to National Cancer Institute Common Terminology Criteria for Adverse Events [version 3.0]). The most common adverse events were diarrhea (18.2% of patients with grade 3) and rash (13.6% of patients with grade 3). The primary objective was met; the median overall survival was 10.7 months (90% confidence interval [90% CI], 8.7-12.9 months). The overall response rate was 25% (90% CI, 15%-38%). The median progression-free survival was 4.2 months (90% CI, 3.6-5.1 months). The results were not substantially different when subdivided by p16 status. Only 2 patients were positive for human epidermal growth factor receptor 2 by immunohistochemistry. CONCLUSIONS: The current study met its primary objective of survival comparable to the combination of cisplatin, 5-FU and cetuximab regimen, and the toxicity of this all-oral regimen was tolerable. Cancer 2016;122:2350-2355. © 2016 American Cancer Society.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/patologia , Idoso , Capecitabina/administração & dosagem , Carcinoma de Células Escamosas/mortalidade , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Lapatinib , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Quinazolinas/administração & dosagem , Retratamento , Carcinoma de Células Escamosas de Cabeça e Pescoço , Resultado do Tratamento
6.
Oncologist ; 18(8): 947-53, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23918070

RESUMO

Most patients with lung cancer have non-small cell lung cancer (NSCLC) subtype and have advanced disease at the time of diagnosis. Improvements in both first-line and subsequent therapies are allowing longer survival and enhanced quality of life for these patients. The median overall survival observed in many second-line trials is approximately 9 months, and many patients receive further therapy after second-line therapy. The cytotoxic agents pemetrexed and docetaxel and the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) erlotinib and gefitinib are standard second-line therapies. For patients with EGFR mutation, a TKI is the favored second-line therapy if not already used in first-line therapy. For patients without the EGFR mutation, TKIs are an option, but many oncologists favor cytotoxic therapy. The inhibitor of the EML4/ALK fusion protein, crizotinib, has recently become a standard second-line treatment for patients with the gene rearrangement and has promise for patients with the ROS1 rearrangement.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Inibidores de Proteínas Quinases/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Docetaxel , Receptores ErbB/antagonistas & inibidores , Cloridrato de Erlotinib , Gefitinibe , Glutamatos/administração & dosagem , Guanina/administração & dosagem , Guanina/análogos & derivados , Humanos , Mutação , Proteínas de Fusão Oncogênica/antagonistas & inibidores , Proteínas de Fusão Oncogênica/genética , Pemetrexede , Proteínas Tirosina Quinases/genética , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas p21(ras) , Quinazolinas/administração & dosagem , Taxoides/administração & dosagem , Proteínas ras/genética
7.
Otolaryngol Head Neck Surg ; 167(5): 846-851, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35259033

RESUMO

OBJECTIVE: To compare oncologic outcomes in sinonasal squamous cell carcinoma (SNSCC) treated with standard of care (SOC) definitive therapy, consisting of surgery or chemoradiotherapy, vs induction therapy followed by definitive therapy. STUDY DESIGN: Retrospective review. SETTING: Academic tertiary care hospital. METHODS: The medical records of patients with biopsy-proven SNSCC treated between 2000 and 2020 were reviewed for demographics, tumor characteristics, staging, treatment details, and oncologic outcomes. Patients were matched 1-to-1 by age, sex, and cancer stage according to treatment received. Time-to-event analyses were conducted. RESULTS: The analysis included 26 patients with locally advanced SNSCC who received either induction therapy (n = 13) or SOC (n = 13). Baseline demographics, Charlson Comorbidity Index, and median follow-up time were well balanced. Weekly cetuximab, carboplatin, and paclitaxel were the most common induction regimen utilized. Tolerance and safety to induction were excellent. Objective responses were observed in 11 of 13 patients receiving induction. No difference in disease-free survival was found between the induction and SOC groups at 1 or 3 years. However, when compared with SOC, induction therapy resulted in significant improvement in overall survival at 2 years (100% vs 65.3%, P = .043) and 3 years (100% vs 48.4%, P = .016) following completion of definitive therapy. Two patients in the SOC group developed metastatic disease, as compared with none in the induction group. CONCLUSIONS: Induction therapy was safe and effective. When compared with SOC, induction therapy improved 3-year overall survival.


Assuntos
Quimioterapia de Indução , Neoplasias dos Seios Paranasais , Humanos , Padrão de Cuidado , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Neoplasias dos Seios Paranasais/patologia , Quimiorradioterapia , Paclitaxel , Estadiamento de Neoplasias
8.
J Immunother Cancer ; 8(2)2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33004541

RESUMO

BACKGROUND: Combination treatment with chemotherapy and immune checkpoint inhibitors (ICIs) has demonstrated meaningful clinical benefit to patients. However, chemotherapy-induced damage to the immune system can potentially diminish the efficacy of chemotherapy/ICI combinations. Trilaciclib, a highly potent, selective and reversible cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor in development to preserve hematopoietic stem and progenitor cells and immune system function during chemotherapy, has demonstrated proof of concept in recent clinical trials. Furthermore, CDK4/6 inhibition has been shown to augment T-cell activation and antitumor immunity in preclinical settings. Therefore, addition of trilaciclib has the potential to further enhance the efficacy of chemotherapy and ICI combinations. METHODS: In murine syngeneic tumor models, a schedule of 3 weekly doses of trilaciclib was combined with chemotherapy/ICI regimens to assess the effect of transient CDK4/6 inhibition on antitumor response and intratumor T-cell proliferation and function. Peripheral T-cell status was also analyzed in patients with small cell lung cancer (SCLC) treated with chemotherapy with or without trilaciclib to gain insights into the effect of transient exposure of trilaciclib on T-cell activation. RESULTS: Preclinically, the addition of trilaciclib to chemotherapy/ICI regimens enhanced antitumor response and overall survival compared with chemotherapy and ICI combinations alone. This effect is associated with the modulation of the proliferation and composition of T-cell subsets in the tumor microenvironment and increased effector function. Transient exposure of trilaciclib in patients with SCLC during chemotherapy treatment both preserved and increased peripheral lymphocyte counts and enhanced T-cell activation, suggesting that trilaciclib not only preserved but also enhanced immune system function. CONCLUSIONS: Transient CDK4/6 inhibition by trilaciclib was sufficient to enhance and prolong the duration of the antitumor response by chemotherapy/ICI combinations, suggesting a role for the transient cell cycle arrest of tumor immune infiltrates in remodeling the tumor microenvironment. These results provide a rationale for combining trilaciclib with chemotherapy/ICI regimens to improve antitumor efficacy in patients with cancer.


Assuntos
Quinase 4 Dependente de Ciclina/metabolismo , Quinase 6 Dependente de Ciclina/metabolismo , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Ativação Linfocitária/efeitos dos fármacos , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Animais , Feminino , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Neoplasias Pulmonares/patologia , Camundongos , Carcinoma de Pequenas Células do Pulmão/patologia
9.
Clin Lung Cancer ; 17(2): 128-32, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26774201

RESUMO

INTRODUCTION: Bevacizumab- and pemetrexed-based therapies have demonstrated activity in patients with non-small-cell lung cancer (NSCLC) and nonsquamous histologic features. Patients with history of never or light smoking might derive greater benefit from these therapies. PATIENTS AND METHODS: The included patients had stage IIIB (malignant pleural effusion) or IV NSCLC with nonsquamous histologic features, adequate organ function, no contraindications to bevacizumab, and no previous cytotoxic therapy. The patients had also never smoked or had smoked ≤ 10 pack years and had quit ≥ 1 year before enrollment. The patients had received 4 cycles of carboplatin (area under the curve, 6), pemetrexed 500 mg/m(2), and bevacizumab 15 mg/kg. Patients without disease progression initiated maintenance therapy with pemetrexed and bevacizumab. A single-arm phase II trial with the primary endpoint of progression-free survival (PFS) was performed. The secondary endpoints were the objective response rate (ORR), overall survival (OS), and toxicity. RESULTS: From March 2010 to November 2013, 38 eligible patients were enrolled and treated in the trial. The most common histologic type was adenocarcinoma (97%). Most of the patients were women (66%) and never smokers (63%). The median PFS was 12.6 months (95% confidence interval [CI], 8.0-23.9 months). The ORR and OS were 47% (95% CI, 31%-64%) and 20.3 months (95% CI, 15.8-30.5 months). The grade 3 or 4 toxicities occurring at rate of ≥ 10% were neutropenia (18%), anemia (16%), fatigue (16%), hypertension (16%), and thrombocytopenia (11%). CONCLUSION: The combination of the carboplatin, pemetrexed, and bevacizumab demonstrated activity with acceptable toxicity in patients with a clinical history of never or light smoking.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia/etiologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/administração & dosagem , Bevacizumab/efeitos adversos , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neutropenia/etiologia , Pemetrexede/administração & dosagem , Pemetrexede/efeitos adversos , Fumar , Análise de Sobrevida , Resultado do Tratamento , Estados Unidos
10.
Adv Radiat Oncol ; 1(2): 115-121, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28740878

RESUMO

PURPOSE: Accurate assessment of toxicity allows for timely delivery of supportive measures during radiation therapy for head and neck cancer. The current paradigm requires weekly evaluation of patients by a provider. The purpose of this study is to evaluate the feasibility of monitoring patient reported symptoms via mobile devices. METHODS AND MATERIALS: We developed a mobile application for patients to report symptoms in 5 domains using validated questions. Patients were asked to report symptoms using a mobile device once daily during treatment or more often as needed. Clinicians reviewed patient-reported symptoms during weekly symptom management visits and patients completed surveys regarding perceptions of the utility of the mobile application. The primary outcome measure was patient compliance with mobile device reporting. Compliance is defined as number of days with a symptom report divided by number of days on study. RESULTS: There were 921 symptom reports collected from 22 patients during treatment. Median reporting compliance was 71% (interquartile range, 45%-80%). Median number of reports submitted per patient was 34 (interquartile range, 21-53). Median number of reports submitted by patients per week was similar throughout radiation therapy and there was significant reporting during nonclinic hours. Patients reported high satisfaction with the use of mobile devices to report symptoms. CONCLUSIONS: A substantial percentage of patients used mobile devices to continuously report symptoms throughout a course of radiation therapy for head and neck cancer. Future studies should evaluate the impact of mobile device symptom reporting on improving patient outcomes.

11.
Lung Cancer ; 86(2): 288-90, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25201721

RESUMO

OBJECTIVES: Platinum-based chemotherapy with bevacizumab is a standard therapy for patients with stage IIIB/IV non-small cell lung cancer (NSCLC) with non-squamous (NS) histology. Mechanisms of resistance to bevacizumab include increased VEGF signaling or activation of VEGF receptors. Pazopanib is a multi-targeted VEGF receptor tyrosine kinase with single agent activity in NSCLC. MATERIALS AND METHODS: Stage IIIB/IV patients with adequate organ function, who progressed on a bevacizumab containing therapy were eligible if it had been ≤8 weeks since the last bevacizumab treatment. The primary end-point was disease control rate (DCR), defined as partial or complete response, or stable disease for ≥12 weeks. Patients were assessed radiographically every 2 cycles (6 weeks). A Simon 2-stage design was used, and if in the first stage ≤4 of 17 patients experienced disease control the trial was to have been stopped for futility. An unplanned analysis was performed after 15 patients were evaluable secondary to slow accrual. RESULTS: Between December 2010 and November 2013, 15 patients were treated on trial. The median age was 61 years (range 39-74), and all patients had stage IV disease. Of the 15 patients, 4 discontinued therapy prior to cycle 2 evaluation due to adverse events (n=3) and medical illness (n=1), 5 patients had progressive disease, 4 patients had stable disease for <12 weeks, and 2 patients had stable disease for ≥12 weeks. No responses were observed. The DCR observed was 13% (2/15), and the trial did not meet the criteria to proceed to the second stage. Episodes of grade 3 treatment related toxicities observed included: increased ALT (n=2), increased AST (n=1), anorexia (n=3), fatigue (n=3), hypertension (n=1), infection (n=1), mucositis (n=2), nausea (n=3), pericardial effusion (n=1), and vomiting (n=1). CONCLUSION: Pazopanib has limited activity in NSCLC-NS in patients who have experienced disease progression on bevacizumab.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Adulto , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Bevacizumab , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Progressão da Doença , Feminino , Humanos , Indazóis , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pirimidinas/administração & dosagem , Sulfonamidas/administração & dosagem , Resultado do Tratamento
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