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1.
Int J Gynecol Cancer ; 2022 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-35318277

RESUMO

BACKGROUND: Poly (ADP-ribose) polymerase inhibitors have transformed the management landscape for patients with ovarian cancer, demonstrating remarkable improvements in progression-free survival and overall survival. Unfortunately, most relapses are due to an acquired mechanism of resistance to these agents. We hypothesize that secondary cytoreductive surgery, removing resistant clones, might help to overcome the development of resistance to poly (ADP-ribose) polymerase inhibitors, prolonging their therapeutic effect. PRIMARY OBJECTIVE: To determine the efficacy of olaparib beyond progression compared with standard platinum-based chemotherapy in patients with recurrent ovarian cancer progressed during or after poly (ADP-ribose) polymerase inhibitor maintenance therapy after secondary cytoreductive surgery. STUDY HYPOTHESIS: Olaparib administered beyond progression is more effective in increasing progression-free survival and progression-free survival 2 compared with second-line platinum-based chemotherapy in patients after secondary cytoreductive surgery. TRIAL DESIGN: Phase III, randomized, open-label, multicenter trial. Eligible patients will be randomized in a 1:1 ratio to receive olaparib or platinum-based chemotherapy of the investigator's choice. MAJOR ELIGIBILITY CRITERIA: Eligible patients must have high-grade serous or endometrioid ovarian cancer progressed during or after first-line poly (ADP-ribose) polymerase inhibitor maintenance therapy and must have undergone secondary cytoreductive surgery. PRIMARY ENDPOINT: The dual primary endpoints will include progression-free survival and progression-free survival 2. Progression-free survival is defined by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as the time between randomization and progression or death from any cause. Progression-free survival 2 is defined by the investigator using RECIST version 1.1 as the time frame from randomization to the second progression or death from any cause after subsequent treatment. SAMPLE SIZE: Approximately 200 patients will be enrolled in this study. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Enrollment will be completed in 2024. Results will be presented in 2026. TRIAL REGISTRATION: EudraCT 2021-000245-41 NCT05255471.

3.
Life (Basel) ; 11(11)2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34833129

RESUMO

Randomized clinical trials are considered the milestones of clinical research in oncology, and guided the development and approval of new compounds so far. In the last few years, however, molecular and genomic profiling led to a change of paradigm in therapeutic algorithms of many cancer types, with the spread of different biomarker-driven therapies (or targeted therapies). This scenario of "personalized medicine" revolutionized therapeutic strategies and the methodology of the supporting clinical research. New clinical trial designs are emerging to answer to the unmet clinical needs related to the development of these targeted therapies, overcoming the "classical" structure of randomized studies. Innovative trial designs able to evaluate more than one treatment in the same group of patients or many groups of patients with the same treatment (or both) are emerging as a possible future standard in clinical trial methodology. These are identified as "master protocols", and include umbrella, basket and platform trials. In this review, we described the main characteristics of these new trial designs, focusing on the opportunities and limitations of their use in the era of personalized medicine.

5.
Cancers (Basel) ; 13(20)2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34680301

RESUMO

BACKGROUND: Epithelial ovarian cancer (EOC) is a rare, highly lethal disease. In a subset of high grade EOC patients, maintenance therapy with the antiangiogenic drug Bevacizumab (BEV) is a valuable option. To date, no validated predictive or prognostic biomarkers exist for selecting EOC patients that might benefit from BEV treatment. METHODS: Immunohistochemistry and RT-qPCR evaluated the expression of seven angiogenesis-related proteins and of a twelve microRNAs angio-signature in EOC patients, treated in first line with chemotherapy plus BEV (MITO16A/ManGO OV-2 phase IV trial). Centralized statistical analyses assessed the associations between each biomarker, clinical prognostic factors and survival outcomes. RESULTS: High miR-484 expression was associated with longer progression-free and overall survival. Notably, the combined expression of miR-484 and its target VEGFB identified a subset of patients that might mostly benefit from BEV treatment. No other significant correlations were found between the other analyzed biomarkers and patients' survival. The application of a shrinkage procedure to adjust for over-fitting hazard ratio estimates reduced the association significance. CONCLUSIONS: The analysis of angiogenesis related biomarkers in EOC patients homogenously treated with BEV in first line provides novel insight in their prognostic value and suggests that some of them might merit to be tested as predictive markers of drug activity in dedicated randomized trials.

6.
Int J Gynecol Cancer ; 31(10): 1348-1355, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34462317

RESUMO

INTRODUCTION: The use of routine antithrombotic prophylaxis is not recommended for advanced cancer patients receiving chemotherapy. The effect of bevacizumab-containing therapy on the risk of thromboembolic events remains controversial in ovarian cancer patients. We report on the incidence of thromboembolic events and the prevalence of antithrombotic therapy in patients enrolled in the single arm, phase IV, MITO-16A/MaNGO-OV2A trial. METHODS: In this trial, potential prognostic factors for patients with previously untreated ovarian cancer receiving a combination of platinum-based chemotherapy and bevacizumab were explored and the final analysis has already been reported. In this secondary analysis, the occurrence of thromboembolic events and the use of antithrombotic therapy were described according to the clinical characteristics of the patients. The prognostic role of thromboembolic events for progression-free and overall survival were also evaluated. RESULTS: From October 2012 to November 2014, 398 eligible patients were enrolled. 76 patients (19.1%) were receiving some type of anticoagulant or anti-aggregant treatment at baseline. Overall, 24 thromboembolic events were reported (cumulative incidence of 6.0%). The occurrence of thromboembolic events was not associated with baseline patient characteristics and was not modified by the use of antithrombotic prophylaxis (HR 0.60, 95% CI 0.18 to 2.0). Occurrence of thromboembolic events was not associated with progression-free survival (HR 1.34, 95% CI 0.83 to 2.15) or overall survival (HR 0.78, 95% CI 0.37 to 1.61). CONCLUSIONS: In our study, a 6.0% rate of thromboembolic events was reported during treatment with bevacizumab plus chemotherapy. Thromboembolic events were not associated with the clinical characteristics of the patients or with the use of antithrombotic prophylaxis, nor did they significantly affect the long-term prognosis. TRIAL REGISTRATION NUMBER: NCT01706120.


Assuntos
Carcinoma Epitelial do Ovário/tratamento farmacológico , Fibrinolíticos/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Tromboembolia/prevenção & controle , Idoso , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica , Bevacizumab/administração & dosagem , Bevacizumab/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade
7.
BMC Cancer ; 21(1): 549, 2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-33985435

RESUMO

BACKGROUND: Chemotherapy-induced neutropenia (CIN) has been demonstrated to be a prognostic factor in several cancer conditions. We previously found a significant prognostic value of CIN on overall survival (OS), in a pooled dataset of patients with advanced non-small-cell lung cancer (NSCLC) receiving first line chemotherapy from 1996 to 2001. However, the prognostic role of CIN in NSCLC is still debated. METHODS: We performed a post hoc analysis pooling data prospectively collected in six randomized phase 3 trials in NSCLC conducted from 2002 to 2016. Patients who never started chemotherapy and those for whom toxicity data were missing were excluded. Neutropenia was categorized on the basis of worst grade during chemotherapy: absent (grade 0), mild (grade 1-2), or severe (grade 3-4). The primary endpoint was OS. Multivariable Cox model was applied for statistical analyses. In the primary analysis, a minimum time (landmark) at 180 days from randomization was applied in order to minimize the time-dependent bias. RESULTS: Overall, 1529 patients, who received chemotherapy, were eligible; 572 of them (who received 6 cycles of treatment) represented the landmark population. Severe CIN was reported in 143 (25.0%) patients and mild CIN in 135 (23.6%). At multivariable OS analysis, CIN was significantly predictive of prognosis although its prognostic value was entirely driven by severe CIN (hazard ratio [HR] of death 0.71; 95%CI: 0.53-0.95) while it was not evident with mild CIN (HR 1.21; 95%CI: 0.92-1.58). Consistent results were observed in the out-of-landmark group (including 957 patients), where both severe and mild CIN were significantly associated with a reduced risk of death. CONCLUSION: The pooled analysis of six large trials of NSCLC treatment shows that CIN occurrence is significantly associated with a longer overall survival, particularly in patients developing severe CIN, confirming our previous findings.


Assuntos
Antineoplásicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Neutropenia/induzido quimicamente , Idoso , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Neutropenia/terapia , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos
8.
J Transl Med ; 18(1): 405, 2020 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-33087150

RESUMO

BACKGROUND: Tocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients. METHODS: A multicenter, single-arm, hypothesis-driven trial was planned, according to a phase 2 design, to study the effect of tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints, a priori expected rates being 20 and 35%, respectively). A further prospective cohort of patients, consecutively enrolled after the first cohort was accomplished, was used as a secondary validation dataset. The two cohorts were evaluated jointly in an exploratory multivariable logistic regression model to assess prognostic variables on survival. RESULTS: In the primary intention-to-treat (ITT) phase 2 population, 180/301 (59.8%) subjects received tocilizumab, and 67 deaths were observed overall. Lethality rates were equal to 18.4% (97.5% CI: 13.6-24.0, P = 0.52) and 22.4% (97.5% CI: 17.2-28.3, P < 0.001) at 14 and 30 days, respectively. Lethality rates were lower in the validation dataset, that included 920 patients. No signal of specific drug toxicity was reported. In the exploratory multivariable logistic regression analysis, older age and lower PaO2/FiO2 ratio negatively affected survival, while the concurrent use of steroids was associated with greater survival. A statistically significant interaction was found between tocilizumab and respiratory support, suggesting that tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline. CONCLUSIONS: Tocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Possibly, this effect could be limited to patients not requiring mechanical respiratory support at baseline. Registration EudraCT (2020-001110-38); clinicaltrials.gov (NCT04317092).


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus/imunologia , COVID-19 , Estudos de Coortes , Infecções por Coronavirus/epidemiologia , Feminino , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Mortalidade , Uso Off-Label , Pandemias , Pneumonia Viral/epidemiologia , SARS-CoV-2 , Resultado do Tratamento , Estudos de Validação como Assunto
9.
Int J Mol Sci ; 21(18)2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32962091

RESUMO

Fibroblast growth factor receptors (FGFRs) are tyrosine kinase receptors involved in many biological processes. Deregulated FGFR signaling plays an important role in tumor development and progression in different cancer types. FGFR genomic alterations, including FGFR gene fusions that originate by chromosomal rearrangements, represent a promising therapeutic target. Next-generation-sequencing (NGS) approaches have significantly improved the discovery of FGFR gene fusions and their detection in clinical samples. A variety of FGFR inhibitors have been developed, and several studies are trying to evaluate the efficacy of these agents in molecularly selected patients carrying FGFR genomic alterations. In this review, we describe the most frequent FGFR aberrations in human cancer. We also discuss the different approaches employed for the detection of FGFR fusions and the potential role of these genomic alterations as prognostic/predictive biomarkers.


Assuntos
Terapia de Alvo Molecular/métodos , Neoplasias/metabolismo , Neoplasias/terapia , Receptores de Fatores de Crescimento de Fibroblastos/antagonistas & inibidores , Receptores de Fatores de Crescimento de Fibroblastos/genética , Progressão da Doença , Fusão Gênica , Genômica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Mutação , Neoplasias/diagnóstico , Neoplasias/genética , Receptores de Fatores de Crescimento de Fibroblastos/metabolismo , Transdução de Sinais
10.
Gynecol Oncol ; 154(1): 83-88, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31029508
11.
Curr Pharm Des ; 20(24): 3894-900, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24138713

RESUMO

The epidermal growth factor receptor (EGFR) is among the most important targets in the treatment of advanced non-small cell lung cancer (NSCLC). Erlotinib and gefitinib, two small molecules, are reversible EGFR tyrosine kinase inhibitors (TKIs). Non-small cell lung cancers with EGFR mutations, are characterized by excellent responses when treated with the EGFR-TKIs gefitinib and erlotinib. However, all the patients with tumors harbouring EGFR mutations experience disease progression after a median of 10 to 14 months of treatment with gefitinib or erlotinib. A group of new generation EGFR-TKIs irreversibly inhibit EGFR-TK and represent one of the strategies that may potentially overcome the acquired resistance to gefitinib and erlotinib or achieve better outcomes than reversible inhibitors in the first-line treatment of EGFR mutant lung cancers. Afatinib (BIBW 2992) and PF299804 are the irreversible EGFR-TKIs with the most relevant data in the treatment of advanced NSCLC, as primary EGFR-targeted therapy and after resistance to reversible EGFR-TKIs. However, to date, the role of irreversible EGFR inhibitors remains to be defined.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Receptores ErbB/antagonistas & inibidores , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Progressão da Doença , Receptores ErbB/genética , Receptores ErbB/metabolismo , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Mutação
12.
Curr Pharm Des ; 19(30): 5333-43, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23394083

RESUMO

Lung cancer is the leading cause of mortality world-wide. Non Small Cell Lung Cancer (NSCLC) is a particularly aggressive cancer, the optimum management of which is still being determined. In the next years modest survival improvement can be expected by chemotherapy. Advances in understanding of the molecular pathogenesis of lung cancer have led to the identification of several specific targets for therapeutic agents. Targeting the epidermal growth factor receptor (EGFR) has played a central role in advancing NSCLC research, treatment, and patient outcome over the last several years. In lung cancer, 10-15% of NSCLC contain activating mutations in the EGFR kinase conferring hypersensitivity to the oral TKIs gefitinib and erlotinib, have been demonstrated to be important predictive factors when selecting patients to be treated with these two agents. More recently, another molecular abnormality, the translocation of the anaplastic lymphoma kinase (ALK) gene that drives NSCLC in a different group of patients has been found in 4 to 5% of NSCLC. The rearrangement results in an EML4 - AKL fusion gene, which increases ALK activity. Inhibitors of ALK kinase have been developed and investigated. Crizotinib, an orally ALK and met proto-oncogene (MET) inhibitor, was very well tolerated and produced dramatic antitumor activity in early-stage trials which facilitated a faster than normal move into late-stage trials for EML4-ALK -positive NSCLC patients treatment. In a phase III randomized that showed progression free survival benefit as compared to chemotherapy in second-line setting. Several novel selective inhibitors of ALK kinase are currently in preclinical or early clinical testing. Since the discovery that Met pathway is one of the most frequently dysregulated pathways in human cancer, Met inhibitors, with varying kinase selectivity profiles ranging from highly selective to multi-targeted have been studied in the clinic and good progress has been achieved. A number of studies suggest that the PI3K/Akt signaling pathway is central to NSCLC growth and survival. Given the importance of activated PI3K signaling in cancer, several PI3K inhibitors are currently one of the most recent drug targets in oncology, with several small molecules in early stages of clinical development. This review will focus on the role of EGFR, ALK, MET, and PI3K inhibitors in the treatment of NSCLC.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Desenho de Fármacos , Inibidores Enzimáticos/uso terapêutico , Regulação Neoplásica da Expressão Gênica , Humanos
13.
Curr Pharm Des ; 18(37): 6155-68, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22873759

RESUMO

Lung cancer, of which non-small-cell lung cancer (NSCLC) is the most common form, remains the leading cause of cancer-related mortality worldwide, with many patients presenting with advanced disease at initial diagnosis. In advanced NSCLC patients whose tumors harbor activating epidermal growth factor receptor (EGFR) mutations, the use of EGFR tyrosine kinase inhibitors (TKIs) as first-line treatment has provided an unusually large progression-free-survival (PFS) benefit, a significantly high response rate (RR) and decreased toxicity when compared with cytotoxic chemotherapy in several phase III randomized trials; however, resistance invariably occurs. There are multiple mechanisms defined by which tumor cells may become independent of EGFR such as the well-characterized example of mesenchymal-epithelial transition factor (MET) amplification. Upon initial diagnosis of NSCLC, MET gene amplification is uncommon; however, acquired MET amplification has been noted in up to 20% of EGFR-mutated tumors that have been pretreated with an EGFR TKI. In tumors containing MET gene amplification, stimulation of the tumor occurs via the co-receptor HER-3 resulting in activation of the phosphatidylinositol-3-kinase (PI3K) signaling pathway, thereby circumventing the effects of an EGFR TKI. Recently, the targeting of the MET pathway has been attempted with small molecules and with monoclonal antibodies. This review will explain the MET signaling pathway and biology in cancer and the recent clinical development and advances of MET/HGF targeting agents in the treatment of advanced NSCLC.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas c-met/antagonistas & inibidores , Animais , Antineoplásicos/química , Carcinoma Pulmonar de Células não Pequenas/enzimologia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Desenho de Fármacos , Humanos , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Terapia de Alvo Molecular , Inibidores de Proteínas Quinases/química , Proteínas Proto-Oncogênicas c-met/genética , Proteínas Proto-Oncogênicas c-met/metabolismo , Transdução de Sinais/efeitos dos fármacos
14.
Expert Rev Vaccines ; 10(6): 887-97, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21692707

RESUMO

Non-small-cell lung cancer (NSCLC) is not considered to be immunogenic, but it may provide an accessible target for the properly primed immune system. Identifying lung tumor antigens and presenting them in the optimal context may enable the immune system to generate anti-lung tumor effector cells, which are usually absent. Despite encouraging preclinical and Phase I-II data, no specific active cancer vaccine has been approved for NSCLC therapy to date. Patient selection and measurable immune response methodology assessment could explain these negative results. Vaccine therapy has recently been re-emerging as a potential approach. This article discusses the Phase I, II and III trials investigating the most promising vaccines in the treatment of patients affected by any stage of NSCLC, thus providing a perspective on the future of this approach in this setting.


Assuntos
Vacinas Anticâncer/administração & dosagem , Vacinas Anticâncer/imunologia , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Biomarcadores/análise , Técnicas de Laboratório Clínico/métodos , Ensaios Clínicos como Assunto , Humanos , Seleção de Pacientes , Resultado do Tratamento
15.
Clin Adv Hematol Oncol ; 9(5): 375-83, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21685866

RESUMO

To date, lung cancer is still the leading cause of cancer-related mortality worldwide, with the majority of lung cancers arising in the elderly. As a consequence, we can expect an increase in the number of older lung cancer patients considered suitable for chemotherapy in the near future. Elderly patients often have comorbid conditions and progressive physiologic reduction of organ function, which can make the selection of proper treatment daunting. Some patients will be able to tolerate chemotherapy as well as their younger counterparts, whereas others will experience severe toxicity and require treatment modifications. Thus, a major issue is effectively selecting patients suitable for standard or attenuated therapy. A comprehensive geriatric assessment performed at baseline is a useful tool that can help select the best treatment regimen to be administered to elderly patients. Until now, few trials have specifically focused on elderly patients affected by non-small cell lung cancer (NSCLC), particularly those with advanced disease; prospective elderly-specific studies in early stages are still lacking. High priority should be given to evaluating the role of new targeted therapies. Unfortunately, to date, clinical trials that include functional status and comorbidity as part of the geriatric assessment are rare. Future trials, specifically in the elderly population, should include these kinds of evaluations. The most recent therapies for the treatment of elderly patients with NSCLC will be discussed here.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Idoso , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/patologia , Quimioterapia Adjuvante , Ensaios Clínicos como Assunto , Humanos , Neoplasias Pulmonares/patologia , Terapia de Alvo Molecular , Estadiamento de Neoplasias
16.
Target Oncol ; 6(3): 171-80, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21409591

RESUMO

Lung cancer is the most common cancer in the world. One third of patients with non-small cell lung cancer (NSCLC) are diagnosed with locally or regionally advanced unresectable disease at presentation. Currently, in this stage of disease, a combination of chemotherapy and radiotherapy is the standard treatment approach for patients with good performance status, and concomitant chemo-radiotherapy has demonstrated to be the best therapeutic approach. However, despite improvements in treatment, local tumor control remains suboptimal and distant metastases remain the major site of failure. The diversity of molecular abnormalities in NSCLC may partly contribute to its resistance to therapy. It is therefore widely accepted that one approach to improve the efficacy of cancer therapy is the development of rational combinations of anticancer agents that may exhibit synergistic interactions. The introduction of several biologic agents represents an important advance in the management of NSCLC and some of them have shown to have a synergistic effect when given in combination with radiotherapy and chemotherapy in preclinical and in clinical models. In the present review we discuss the rationale and the feasibility of these combinations and the first results available from clinical trials.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/terapia , Terapia de Alvo Molecular/métodos , Vacinas Anticâncer/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Terapia Combinada , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/radioterapia
17.
Expert Opin Drug Saf ; 10(2): 311-7, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21261558

RESUMO

INTRODUCTION: For patients with advanced NSCLC, treatment outcomes are still disappointing and the search for new active and safe drugs is warranted. The chemotherapeutic agent pemetrexed has produced, in the last years, an innovation of therapeutic algorithms of this disease, and this review is aimed at describing the role of pemetrexed in the treatment of NSCLC. AREAS COVERED: In the present review, we discuss the mechanism of action of pemetrexed, its safety profile and the main clinical data on pemetrexed in NSCLC treatment. The reader will gain information on pemetrexed efficacy in the first-line, second-line and maintenance treatment of advanced NSCLC. Moreover, the histotype-based approach to NSCLC treatment, which is important for the selection of patients to be treated with pemetrexed, is clarified. EXPERT OPINION: The recent introduction of pemetrexed in the first-line and maintenance treatment of advanced non-squamous NSCLC represents, in our opinion, a significant step forward in the treatment of this disease in the last 3 years. Furthermore, cisplatin plus pemetrexed has a more favorable safety profile as compared with those of pre-existing cisplatin-based regimens.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Glutamatos/uso terapêutico , Guanina/análogos & derivados , Neoplasias Pulmonares/tratamento farmacológico , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/patologia , Cisplatino/administração & dosagem , Glutamatos/administração & dosagem , Glutamatos/efeitos adversos , Guanina/administração & dosagem , Guanina/efeitos adversos , Guanina/uso terapêutico , Humanos , Neoplasias Pulmonares/patologia , Pemetrexede
18.
Rev Recent Clin Trials ; 6(1): 44-51, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20868346

RESUMO

Platinum-based chemotherapy, with or without the antiangiogenetic drug bevacizumab, is the standard first-line therapy for patients with advanced non-small-cell lung cancer (NSCLC). The epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) gefitinib has been recently approved as treatment of patients with EGFR mutated tumors (including first-line). Three agents are approved for treating non-selected patients who progress after one prior regimen: docetaxel, pemetrexed, and the EGFR-TKI erlotinib. Gefitinib can be used as second-line treatment in patients with EGFR mutated tumors. Although these agents have yelded similar outcomes in terms of antitumor activity and efficacy in unselected NSCLC patients, they have different toxicity profiles, and recently some strong factors that can help in the choice among them have been detected. In particular, the hystotype, the EGFR gene mutational status, the response to previous first-line chemotherapy and the correlation of the safety profile of the agents with Performance Status and comorbidities of the patients, are the most important factors that drive the choice of the second-line treatment. Obviously, the drugs administered in the first-line treatment strongly influence the choice of the second-line treatment because some of the currently available drugs can be used in both settings. Thus, more than in the past, first and second-line treatment of advanced NSCLC are linked, and the choice of second-line treatment is part of a strategy decided when beginning the first-line treatment.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Tomada de Decisões , Glutamatos/uso terapêutico , Guanina/análogos & derivados , Neoplasias Pulmonares/tratamento farmacológico , Quinazolinas/uso terapêutico , Taxoides/uso terapêutico , Docetaxel , Receptores ErbB/antagonistas & inibidores , Gefitinibe , Guanina/uso terapêutico , Humanos , Pemetrexede , Timidilato Sintase/antagonistas & inibidores
19.
J Thorac Dis ; 3(2): 122-33, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22263075

RESUMO

Lung cancer is the major cause of cancer death in the world. Non Small Cell Lung Cancer (NSCLC) accounts approximately 80-85% of all lung cancer diagnosis; the majority of patients will be diagnosed with non operable, advanced-stage disease. Palliative chemotherapy and/or radiotherapy represent the standard of care of this disease. Platinum based doublets with third generation agents are considered the standard of first line advanced NSCLC treatment. However, data arising from the availability of pemetrexed suggest that histology could play a key role in decision making. Advances in understanding of the molecular pathogenesis of lung cancer have led to the identification of several specific targets such as vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) for therapeutic agents. Bevacizumab is the first recombinant humanized monoclonal antibody (mAb) binding VEGF to demonstrate clinical benefit and a rather survival prolongation in combination with chemotherapy in the treatment of non squamous chemo-naive advanced NSCLC patients. Two types of anti-EGFR targeting agents have reached advanced clinical development: mAbs and small molecule inhibitors of the EGFR tyrosine kinase enzymatic activity (TKIs). Among TKIs gefitinib has been tested in several phase II-III studies showing an improvement in survival and responses in first, second and third line treatment in selected patients with specific clinical and molecular characteristics. Furthermore, erlotinib has showed to significantly improve survival in an unselected population of patients following the failure of one or two chemotherapy regimens. This review will discuss the different therapeutic options for first and second line treatment in the clinical practice.

20.
Clin Lung Cancer ; 11(6): 374-82, 2010 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-21062728

RESUMO

First-line platinum-based chemotherapy has reached a plateau of effectiveness for the treatment of patients with advanced non-small-cell lung cancer (NSCLC). In patients who reported a stable disease, no more than 4 cycles of chemotherapy are recommended while a maximum of 6 cycles is recommended in patients who are responding to therapy. A potential strategy with the aim of improving outcomes for NSCLC patients is to administer more therapy. This term includes different approaches: duration of therapy, sequential therapy, consolidation therapy, and maintenance therapy. Here, we attempt to define the different approaches that fall under the rubric of maintenance strategy, and discuss the results available to date.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Esquema de Medicação , Humanos , Neoplasias Pulmonares/patologia , Compostos de Platina/administração & dosagem , Resultado do Tratamento
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