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1.
Oncotarget ; 12(26): 2514-2530, 2021 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-34966483

RESUMO

Most patients with early HR+ and HER2- breast cancer receive a hormone therapy; the clinical question still open is how to identify patients who can really benefit from adjuvant chemotherapy. The accurate identification of these patients is essential to avoid an over-treatment, increasing the risk of an unnecessary toxicity; on the contrary, the omission of chemotherapy can deprive high risk patients of a potential life-saving treatment (under-treatment). Several multigene assays (MGAs), assessing the risk of relapse according to the biological characteristics of the tumor, have been developed. To date, the 21-gene assay (Oncotype DX Breast Recurrence Score®) is the only test developed and validated to be actionable, i.e., able to predict the benefit of adjuvant chemotherapy. The different available tests can be classified according to their clinical utility based on their prognostic and predictive value. A prognostic test gives information about the outcome of the disease, regardless of the administered therapy. When the aim of the test is to drive the treatment decisions, the predictive component, and therefore the ability to accurately identify which patients could benefit from chemotherapy, is essential. This review summarizes the clinical evidences of the Oncotype DX® test supporting its clinical utility.

2.
NPJ Breast Cancer ; 7(1): 47, 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33953182

RESUMO

Clinicopathological prognostic features have limited value to identify with precision newly diagnosed patients with hormone receptor (HR)-positive, HER2-negative breast cancer (BC), who would benefit from chemotherapy (CT) in addition to adjuvant hormonal therapy (HT). The 21-gene Oncotype DX Breast Recurrence Score® (RS) assay has been demonstrated to predict CT benefit, hence supporting personalized decisions on adjuvant CT. The multicenter, prospective, observational study PONDx investigated the real-life use of RS® results in Italy and its impact on treatment decisions. Physicians' treatment recommendations (HT ± CT) were documented before and after availability of RS results, and changes in recommendations were determined. In the HR+ HER2- early BC population studied (N = 1738), physicians recommended CT + HT in 49% of patients pre-RS. RS-guided treatment decisions resulted in 36% reduction of CT recommendations. PONDx confirms that RS results provide clinically relevant information for CT recommendation in early-stage BC, resulting in a reduction of more than a third of CT use.

3.
Oncotarget ; 12(9): 936-947, 2021 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-33953847

RESUMO

Breast cancer is the most common tumour in women and the first cause of death for cancer in the female population. Preserving the quality of life has therefore become an important objective in the management of the disease. The benefits of adjuvant chemotherapy in patients with HR+ HER2- early breast cancer should always be balanced against its potential short and long-term adverse effects, and identifying the appropriate patients for whom chemotherapy can offer the highest clinical benefit is critical. Besides clinical and pathological factors, today four multigene tests able to guide the choice of the adjuvant therapy early breast cancer are available in Italy: Oncotype DX®, EndoPredict®, MammaPrint® e Prosigna®. This review evaluates the main characteristics of these diagnostic tests, the studies on clinical utility, their economic impact and their inclusion in international and national guidelines. The Oncotype DX Breast Recurrence Score® test is the only multigene test validated, with level IA evidence, to guide the adjuvant therapy decisions: hormone therapy alone for most patients with RS results 0-25, and chemotherapy for patients with RS results 26-100. Clinical data demonstrate that the Oncotype DX test is able to significantly impact therapeutic decisions, reducing chemotherapy use up to 49% and supporting the use of chemotherapy (up to 12%) in potentially under-treated patients. Based on the level of clinical evidence and established clinical utility, several multigene tests have been included in the main international guidelines, with recommendations ranging from "strong" to "moderate".

4.
J Pers Med ; 10(4)2020 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-33353132

RESUMO

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in combination with endocrine therapy (ET) show meaningful efficacy and tolerability in patients with metastatic breast cancer (MBC), but the optimal sequence of ET has not been established. It is not clear if patients with lobular breast carcinomas (LBC) derive the same benefits when receiving second line CDK4/6i. This retrospective study compared the efficacy of palbociclib plus fulvestrant (PALBO-FUL) with everolimus plus exemestane (EVE-EXE) as second-line ET for hormone-resistant metastatic LBC. From 2013 to 2018, patients with metastatic LBC positivity for estrogen and/or progesterone receptors and HER2/neu negativity, who had relapsed during adjuvant hormonal therapy or first-line hormonal treatment, were enrolled from six centers in Italy in this retrospective study. A total of 74 out of 376 patients (48 treated with PALBO-FUL and 26 with EVE-EXE) with metastatic LBC were eligible for inclusion. Progression-free survival (PFS) was longer in patients receiving EVE-EXE compared with PALBO-FUL (6.1 vs. 4.5 months, univariate HR 0.58, 95% CI 0.35-0.96; p = 0.025). On the propensity score (PS) analysis, PFS was confirmed to be significantly longer for patients treated with EVE-EXE compared to PALBO-FUL (6.0 vs. 4.6 months, p = 0.04). This retrospective analysis suggests that EVE-EXE is more effective than PALBO-FUL for second line ET of metastatic LBC, allowing us to speculate on the optimal therapeutic sequence.

5.
Clin Breast Cancer ; 20(5): e600-e611, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32565110

RESUMO

PURPOSE: Oncotype DX (ODX) predicts breast cancer recurrence risk, guiding the choice of adjuvant treatment. In many countries, access to the test is not always available. We used correlation between phenotypical tumor characteristics, quantitative classical immunohistochemistry (IHC), and recurrence score (RS) assessed by ODX to develop a decision supporting system for clinical use. PATIENTS AND METHODS: Breast cancer patients who underwent ODX testing between 2014 and 2018 were retrospectively included in the study. The data selected for analysis were age, menopausal status, and pathologic and IHC features. IHC was performed with standardized quantitative methods. The data set was split into two subsets: 70% for the training set and 30% for the internal validation set. Statistically significant features were included in logistic models to predict RS ≤ 25 or ≤ 20. Another set was used for external validation to test reproducibility of prediction models. RESULTS: The internal set included 407 patients. Mean (range) age was 53.7 (31-80) years, and 222 patients (54.55%) were > 50 years old. ODX results showed 67 patients (16.6%) had RS between 0 and 10, 272 patients between 11 and 25 (66.8%), and 68 patients > 26 (16.6%). Logistic regression analysis showed that RS score (for threshold ≤ 25) was significantly associated with estrogen receptor (P = .004), progesterone receptor (P < .0001), and Ki-67 (P < .0001). Generalized linear regression resulted in a model that had an area under the receiver operating characteristic curve (AUC) of 92.2 (sensitivity 84.2%, specificity 80.1%) and that was well calibrated. The external validation set (183 patients) analysis confirmed the model performance, with an AUC of 82.3 and a positive predictive value of 91%. A nomogram was generated for further prospective evaluation to predict RS ≤ 25. CONCLUSION: RS was related to quantitative IHC in patients with RS ≤ 25, with a good performance of the statistical model in both internal and external validation. A nomogram for enhancing clinical approach in a cost-effective manner was developed. Prospective studies must test this application in clinical practice.


Assuntos
Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Testes Genéticos/métodos , Imuno-Histoquímica/métodos , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Nomogramas , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/genética , Receptor alfa de Estrogênio/metabolismo , Feminino , Perfilação da Expressão Gênica/métodos , Testes Genéticos/economia , Humanos , Imuno-Histoquímica/economia , Antígeno Ki-67/metabolismo , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Prognóstico , Curva ROC , Receptores de Progesterona/metabolismo , Estudos Retrospectivos
6.
Future Oncol ; 16(5): 129-145, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31849236

RESUMO

Targeted agents have significantly prolonged survival and improved response rates in first- and second-line settings of hormone receptor-positive/HER2-negative metastatic breast cancer. Optimal sequencing of the available options may prolong endocrine sensitivity, slow disease progression and delay the need for chemotherapy. However, the optimal treatment sequence remains unclear and therapeutic decisions are complex. We review the latest recommendations and supporting evidence for endocrine therapy in women with hormone receptor-positive/HER2-negative metastatic breast cancer and discuss strategies for the optimal sequential therapy in scenarios of response to endocrine therapy. Although more data are needed to define the best sequence of endocrine treatments, more personalized sequential strategies, which take into account response to previous treatments as well as disease symptoms and safety issues, will be increasingly feasible.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Terapia de Alvo Molecular , Inibidores de Proteínas Quinases/uso terapêutico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Quinase 4 Dependente de Ciclina/genética , Feminino , Humanos , Metástase Neoplásica , Receptor ErbB-2/genética , Receptores de Estrogênio/genética , Receptores de Progesterona/genética
7.
Clin Breast Cancer ; 20(2): e181-e187, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31735691

RESUMO

BACKGROUND: T-DM1 improves progression-free survival (PFS) and overall survival (OS) in patients with metastatic human epidermal growth factor receptor 2-positive (HER2+) breast cancer progressing on prior trastuzumab plus a taxane. A paucity of data is available on T-DM1 efficacy after dual anti-HER2 blockade with pertuzumab and trastuzumab plus a taxane, which represents the current first-line standard of care. The present study is a retrospective/prospective evaluation of the efficacy and activity of second-line T-DM1 after front-line pertuzumab-based therapy. PATIENTS AND METHODS: Eligible patients were identified within the Gruppo Italiano Mammella (GIM) 14/BIOMETA study, a retrospective/prospective multicenter study on treatment patterns and outcomes of patients with metastatic breast cancer (ClinicalTrials.gov Identifier: NCT02284581). We searched for patients who received second-line T-DM1 after taxane plus trastuzumab and pertuzumab between November 15, 2013 and May 31, 2018. We calculated median PFS, median time to treatment failure (TTF), prolonged duration of therapy (PDT), objective response rate (ORR), and 1-year OS. RESULTS: Of 445 patients with HER2+ metastatic breast cancer, 77 were eligible for the analysis. At a median follow-up of 7 months, median PFS was 6.3 months (95% confidence intervals [CI], 4.8-7.7 months), and median TTF was 6.2 months (95% CI, 4-8.6 months). More than one-third of patients (37.6%; n = 29) experienced PDT with an ORR of 27.1%. At data cutoff, the median OS was not reached, and the 1-year OS was 82%. CONCLUSIONS: Our results show meaningful activity of T-DM1 after front-line pertuzumab plus trastuzumab and a taxane, with about 27% of patients having an objective response and 40% of patients achieving durable disease control.


Assuntos
Ado-Trastuzumab Emtansina/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias da Mama/terapia , Recidiva Local de Neoplasia/terapia , Adulto , Idoso , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mama/patologia , Mama/cirurgia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Quimioterapia Adjuvante/métodos , Resistencia a Medicamentos Antineoplásicos , Feminino , Seguimentos , Humanos , Itália/epidemiologia , Mastectomia , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Intervalo Livre de Progressão , Estudos Prospectivos , Receptor ErbB-2/antagonistas & inibidores , Receptor ErbB-2/metabolismo , Estudos Retrospectivos , Trastuzumab/farmacologia , Trastuzumab/uso terapêutico , Falha de Tratamento
8.
BMC Cancer ; 19(1): 36, 2019 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-30621656

RESUMO

BACKGROUND: Unilateral or bilateral metastases to extraocular muscles are very rare in breast cancer. CASE PRESENTATION: We describe a case of inferior rectus extraocular muscle involved by ductal luminal B/Her-2 neu negative breast cancer, observed in a cohort of 580 patients. Our patient had received chemotherapy and hormonal therapy (tamoxifen for 3 years and letrozole in the following 3 years) for her primary cancer and developed an orbital metastasis while she was under aromatase inhibitor-based therapy. Diagnosis was confirmed by MRI and biopsy. Orbital radiotherapy, combined with fulvestrant, resulted in shrinking of the secondary mass. A third line hormonal therapy using palbociclib was then started. Twelve-months later, MRI showed no residual tumor mass. Currently, the patient is alive and in good general conditions after 20 months. CONCLUSIONS: Literature review yielded 57 patients with extraocular muscle metastases from breast cancer, mostly due to the invasive lobular subtype of carcinoma. In addition to the present case, only 4 other extraocular muscles metastases from invasive ductal carcinoma has been reported, pointing out to the rarity of ductal type spread to the orbit in the natural history of breast cancer. Surgery may be used as a single treatment, despite no improvement of symptoms. Radiotherapy alone or combined with chemotherapy, or with chemotherapy plus hormonal therapy are available options. Results are, however, missing or poor. The present case is the first one with complete and stable response after 20 months to radiotherapy, antiestrogen drug fulvestrant and selective inhibitor of CDK4 /CDK6 palbociclib. In this subset of patients, with unusual metastatic sites and frequent multi-organ metastatic impairment, a multidisciplinary approach is indicated in order to achieve the best therapeutic management and long-term surveillance.


Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias Musculares/diagnóstico , Adulto , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Neoplasias Musculares/diagnóstico por imagem , Neoplasias Musculares/patologia , Neoplasias Musculares/secundário , Metástase Neoplásica , Piperazinas/uso terapêutico , Piridinas/uso terapêutico
9.
Anticancer Res ; 38(5): 3105-3110, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29715147

RESUMO

BACKGROUND/AIM: The expression of IL-8 and FGFR has been related to prognosis and pathological features in renal cell carcinoma. We investigated the relationship between IL-8 and FGFR and the outcome in metastatic renal cell carcinoma (mRCC) patients. MATERIALS AND METHODS: Clinical data and histological samples of patients affected by mRCC and treated with targeted agents were reviewed. The expression of proteins was assessed using immunohistochemistry. RESULTS: FGFR1, FGFR2, and IL-8 were found to be expressed in 16%, 30%, and 50% of cases, respectively. Significant correlations were found between selected proteins. A lack of expression of FGFR2 and IL8 was found to be correlated with increased progression-free survival (PFS). The survival rate at 24 months was 44%, 38%, and 79% of those expressing both, one, or none of the evaluated proteins, respectively (p=0.047). CONCLUSION: This analysis found a relationship between the expression of IL-8 and FGFR2 in mRCC patients treated with targeted agents.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Idoso , Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Interleucina-8/análise , Interleucina-8/biossíntese , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/análise , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/biossíntese , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/análise , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/biossíntese , Estudos Retrospectivos
10.
Biomed Res Int ; 2017: 1750925, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29387716

RESUMO

Triple negative breast cancer (TNBC) has an aggressive clinical behaviour, with a poorer prognosis compared to other subtypes. Recently, tumor-infiltrating lymphocytes (TILs) have been proposed as a predictive biomarker for a better clinical outcome and pathological response (pR) after neoadjuvant chemotherapy (NACT) in TNBC. These data confirm the role of the immune system in the neoplastic progression and in the response to therapy. We performed a retrospective analysis of 54 pre-NACT biopsies of TNBC and compared both the percentage of stromal TILs and the degree of PD-L1 expression with the extent of pR to standard NACT. A pathological complete response (pCR) was achieved in 35% of cases. Univariate analysis showed (i) a significant association between PD-L1 expression in ≥25% of neoplastic cells and the achievement of a pCR (p = 0.024); (ii) a significantly higher frequency of pCR in cases showing ≥50% stromal TILs (p < 0.001). However in the multivariate analysis only PD-L1 expression on tumor cells remained significantly associated with pCR (OR = 1,13; 95% CI 1,01-1,27), suggesting that the expression of this biomarker could be associated with a subpopulation of TNBC more likely to respond to chemotherapy. These data need to be confirmed by larger studies.


Assuntos
Antígeno B7-H1/biossíntese , Biomarcadores Tumorais/biossíntese , Regulação Neoplásica da Expressão Gênica , Terapia Neoadjuvante , Proteínas de Neoplasias/biossíntese , Neoplasias de Mama Triplo Negativas , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia
11.
Tumori ; 102(5): 472-480, 2016 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-27647231

RESUMO

PURPOSE: Bevacizumab, a humanized, anti-vascular endothelial growth factor-A monoclonal antibody, has shown efficacy in a number of cancers. However, its use in metastatic breast cancer (MBC) remains controversial. METHODS: A literature review using the PubMed database was performed to update the currently available clinical trials evidence on bevacizumab in the first-line treatment of breast cancer. In addition, the proceedings of selected oncology annual meetings were searched for relevant presentations. RESULTS: This article reviews the available evidence for bevacizumab as first-line therapy for MBC and discusses its current and future applicability in the management of MBC. Three phase III trials (ECOG-2100, AVADO, RIBBON-1) demonstrated that the addition of bevacizumab to chemotherapy is well-tolerated and improves progression-free survival and objective response rates in the first-line setting. These findings were supported by a large clinical practice-based study (ATHENA) and a recent clinical trial in which bevacizumab added to paclitaxel showed notable activity in triple-negative MBC. However, bevacizumab has thus far not demonstrated a significant benefit in overall survival. CONCLUSIONS: The addition of bevacizumab to chemotherapy is well-tolerated and produces substantial improvements in overall response rate and progression-free survival, compared with chemotherapy alone, in advanced HER2-negative breast cancer. Nevertheless, it has thus far not demonstrated a significant benefit in overall survival. Whether prolongation of progression-free survival is enough to consider bevacizumab efficacious is unclear. Based on the available clinical trials results, bevacizumab is a part of the complex therapeutic strategy of advanced HER2-negative breast cancer.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Antineoplásicos/uso terapêutico , Bevacizumab/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Receptor ErbB-2/deficiência , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/efeitos adversos , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/administração & dosagem , Bevacizumab/efeitos adversos , Neoplasias da Mama/patologia , Ensaios Clínicos como Assunto , Feminino , Humanos , Terapia de Alvo Molecular , Estadiamento de Neoplasias , Resultado do Tratamento
12.
Chin J Cancer Res ; 27(5): 488-90, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26543335

RESUMO

The clinical utility of liquid biopsy in cancer treatment will increase as circulating tumor cells (CTCs) analysis move from the enumeration to the real-time measurement of tumor characteristics. Intratumor heterogeneity is becoming increasingly recognized as a major drawback to the shift to personalized medicine. Spatial and temporal heterogeneity might be reflected by the serial assessment of CTCs. Indeed, the developing technologies for CTCs analysis now allow digital genomic and next-generation sequencing approaches, able to differentiate molecular subtypes of the disease and to monitor genetic variation over time. The liquid biopsy of cancer might offer a real-time assessment of tumor biology, providing the opportunity to serially evaluate patients most likely to benefit from targeted drugs based on a dynamic characterization of the disease at the molecular level. Although hurdles remain before liquid biopsy is seen in routine clinical practice, the information derived from CTCs may facilitate the real-time identification of actionable mutations in cancer leading the way toward personalized medicine.

13.
Ther Adv Urol ; 7(5): 286-94, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26425143

RESUMO

Everolimus is an oral inhibitor of mammalian target of rapamycin (mTOR-I) and is currently approved for the treatment of metastatic renal cell carcinoma (mRCC) after failure of first-line vascular endothelial growth factor receptor tyrosine kinase inhibitor (TKI). In this narrative review, we aim to report the available evidence about the use of everolimus as second-line therapy for mRCC. A literature search was performed using PubMed/MEDLINE and abstracts from major conferences on clinical oncology as sources. We report data from prospective as well as retrospective and real world data studies and we analyze the safety and efficacy profile of everolimus as second-line therapy for mRCC. Although different drugs are currently available for the second-line treatment of mRCC, everolimus represents a feasible and safe option in this setting, especially for patients who have experienced high-grade toxicity or are still carrying TKI-related toxicities from first-line treatment.

14.
Onco Targets Ther ; 7: 619-25, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24790460

RESUMO

To date, 10 years after the first demonstration of circulating tumor cells (CTCs), prognostic significance in metastatic breast cancer using the US Food and Drug Administration-cleared system CellSearch(®), the potential utility of CTCs in early clinical development of drugs, their role as a surrogate marker of response to therapy, and their molecular analysis for patient stratification for targeted therapies are still major unsolved questions. Great expectations are pinned on the ongoing interventional trials aimed to demonstrate that CTCs might be of value for guiding treatment of patients and predicting cancer progression. To fill the gap between theory and practice with regard to the clinical utility of CTCs, a bridge is needed, taking into account innovative design for clinical trials, a revised definition of traditional CTCs, next-generation CTC technology, the potential clinical application of CTC analysis in non-validated settings of disease, and finally, expanding the number of patients enrolled in the studies. In this regard, the results of the first European pooled analysis definitely validated the independent prognostic value of CTC counting in metastatic breast cancer patients.

15.
Cancer Treat Rev ; 40(2): 271-5, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24070900

RESUMO

Antiangiogenic agents (AAs) have reported grater efficacy compared to interferon. Despite these advances, radiological complete response to therapy is rare. We meta-analyzed the incidence of complete response in patients treated with AAs and in controls in main randomized clinical trials for first-line therapy in metastatic renal cell carcinoma. PubMed was reviewed for phase II-III randomized clinical trials with AAs vs. non-AAs in patients with good or intermediate prognosis. We calculated the relative risk of events in patients assigned to AAs compared to control. Five RCTs were found; four were phase III and one was phase II. A total of 2747 patients was valuable for final analysis and randomized to receive AAs or control. Patients in the control-group had interferon (85%) or placebo (15%); patients in the AAs-group received bevacizumab (48%), sunitinib (26%), pazopanib (20%) or sorafenib (6%). The incidence of complete response in patients treated with AAs was 2.0% (95% CI, 1.2-2.8) compared to 1.4% (95% CI, 0.7-2.1) in the control arm. Comparing the different type of AAs, the incidence of complete response was 2.5% (95% CI, 1.2-3.8) in the bevacizumab group and 1.6% (95% CI, 0.1-2.5) in the TKIs group. The relative risk to have a complete response was 1.52 (95% CI, 0.85-2.73; p=0.16) in patients treated with AAs compared to controls; this was found higher in patients treated with TKIs compared to bevacizumab. The complete response is a rare event in metastatic kidney tumor, even if AAs reported greater efficacy in terms of progression-free survival and of overall response rate, they did not increase the curative rate of metastatic disease. Probably, some biologic factors other than angiogenesis may influence the complete response in this disease.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Terapia de Alvo Molecular/métodos , Anticorpos Monoclonais Humanizados/administração & dosagem , Bevacizumab , Carcinoma de Células Renais/secundário , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Intervalo Livre de Doença , Humanos , Indazóis , Indóis/administração & dosagem , Quimioterapia de Indução/métodos , Interferons/administração & dosagem , Neoplasias Renais/patologia , Niacinamida/administração & dosagem , Niacinamida/análogos & derivados , Compostos de Fenilureia/administração & dosagem , Prognóstico , Pirimidinas/administração & dosagem , Pirróis/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco , Sorafenibe , Sulfonamidas/administração & dosagem , Sunitinibe , Resultado do Tratamento
16.
Am J Clin Oncol ; 37(6): 611-5, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23388560

RESUMO

Prognosis of metastatic renal cell carcinoma (mRCC) has markedly improved in the recent years. Several factors such as precocious diagnosis, better supportive care, and an increased number of targeted therapies are responsible for this progress. From 2006 to date, 7 drugs have been approved for treatment of mRCC, and among these only 2 are recommended for the second line of therapy with grade 1 evidence. Tyrosine kinase inhibitors (TKIs) and mammalian target of rapamycin (mTOR) inhibitors are the strategies with more evidence, but no comparative studies are available and what is the best second line remains an open issue. Herein, we review the available evidence on the second-line treatment focusing mainly on prospective studies. We identify a special population of patients in whom more evidence is available, and we propose a possible strategy for the management of progressed mRCC and for primary resistant lesions as well as for patients who need a rapid response in lesions. In the majority of patients, several factors should be considered: toxicity reported during first-line therapy, performance status, the absence of correlation between the length of first-line therapy and the probability to respond to second-line therapy, and the lack of comparative trials between mTOR inhibitors and TKI. When an mTOR inhibitor is selected, everolimus must be preferred, although in the RECORD1 trial only the increase in progression-free survival has been reported and the increase in terms of overall survival has not been reached. When another TKI is the choice, there are no strong pieces of evidence that favor the use of a defined molecule. In every case, we recommend to start the selected targeted agents at standard dosage and to pursue therapy as long as possible because the control of disease should be the primary endpoint for the management of mRCC.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/secundário , Neoplasias Renais/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Tirosina Quinases/antagonistas & inibidores , Serina-Treonina Quinases TOR/antagonistas & inibidores , Anticorpos Monoclonais Humanizados/uso terapêutico , Axitinibe , Bevacizumab , Everolimo , Humanos , Imidazóis/uso terapêutico , Indazóis/uso terapêutico , Indóis/uso terapêutico , Niacinamida/análogos & derivados , Niacinamida/uso terapêutico , Compostos de Fenilureia/uso terapêutico , Pirróis/uso terapêutico , Sirolimo/análogos & derivados , Sirolimo/uso terapêutico , Sorafenibe , Sunitinibe , Falha de Tratamento , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores
17.
Acta Oncol ; 51(7): 873-9, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22909392

RESUMO

BACKGROUND: mTOR inhibitors are currently used in the treatment of solid malignancies. Since their approval, several cases of pulmonary toxicity (PT) have been described. This analysis aims to report the incidence and the risk of PT in published randomized controlled trials. MATERIAL AND METHODS: PubMed and Scopus were reviewed for phase II-III randomized controlled trials with temsirolimus and everolimus. The characteristic of each study and incidence of all- and high-grades PT were collected. RESULTS: A total of 2233 patients were available for meta-analysis: 989 had breast cancer, 833 had neuroendocrine tumor and 411 had metastatic renal cell carcinoma. In patients taking mTOR inhibitors, the incidence of all- and high-grades PT was 10.4% and 2.4%, respectively. Compared to controls, the relative risk for all- and high-grades PT was 31- and 8.8-folds, respectively. No significant heterogeneity was observed between the studies. Not any relationship was found between the incidence of lung metastases, treatment exposure and the incidence of PT. CONCLUSIONS: The high grade PT is a rare event and 10% of patients may experience mild grade toxicity with a worsening of quality of life and interruption of therapy in some cases. We recommend monitoring of PT in patients treated with mTOR inhibitors.


Assuntos
Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Pulmão/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Pneumonia/induzido quimicamente , Serina-Treonina Quinases TOR/antagonistas & inibidores , Neoplasias da Mama/tratamento farmacológico , Carcinoma de Células Renais/tratamento farmacológico , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Everolimo , Humanos , Incidência , Neoplasias Renais/tratamento farmacológico , Pulmão/fisiopatologia , Tumores Neuroendócrinos/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Testes de Função Respiratória , Risco , Sirolimo/administração & dosagem , Sirolimo/efeitos adversos , Sirolimo/análogos & derivados
18.
Mol Diagn Ther ; 16(1): 7-11, 2012 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-22303967

RESUMO

Circulating tumor cells (CTCs) are cells of presumed epithelial origin, whose prognostic and predictive value in metastatic cancer patients has recently been demonstrated. To date, the count of CTCs through the CellSearch® system represents a valid approach for monitoring disease status in patients with metastatic colorectal, breast, and prostate cancer; in these cancer types, a rise in the CTC count at any time during treatment predicts a poor outcome. Nevertheless, the clinical utility of monitoring CTC counts remains controversial, and what to do when CTC counts rise during therapy still remains an unanswered question. In this report, we suggest how to integrate CTC counts with their molecular characterization to better translate biologic information obtained on CTCs into daily clinical practice.


Assuntos
Metástase Neoplásica/patologia , Neoplasias/sangue , Neoplasias/patologia , Células Neoplásicas Circulantes/patologia , Antineoplásicos/uso terapêutico , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Prognóstico
19.
Am J Clin Oncol ; 34(6): 625-7, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22101388

RESUMO

Resistance to anthracyclines is responsible for treatment failure in most patients with metastatic breast cancer. According to recent studies, the expression of specific drug transporters (MRPs) on circulating tumor cells is predictive of prognosis in different cancer types. We observed that patients whose circulating tumor cells expressed MRP1 and MRP2, two drug-export pumps responsible for anthracyclines efflux, who received conventional anthracyclines had a significantly shorter time to progression compared with patients sharing same characteristics who received non pegylated liposomal doxorubicin (P < 0.005). These results may highlight a new appealing role of the liposomal doxorubicin formulation, not only because of its reduced cardiac toxicity but especially referring to its theoretical efficacy in anthracycline-resistant breast cancer patients.


Assuntos
Neoplasias da Mama/metabolismo , Resistência a Múltiplos Medicamentos/fisiologia , Resistencia a Medicamentos Antineoplásicos/fisiologia , Proteínas Associadas à Resistência a Múltiplos Medicamentos/biossíntese , Células Neoplásicas Circulantes/metabolismo , Antraciclinas/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Doxorrubicina/uso terapêutico , Feminino , Humanos , Proteína 2 Associada à Farmacorresistência Múltipla , Estadiamento de Neoplasias , Células Neoplásicas Circulantes/patologia
20.
Cancer Biol Ther ; 12(5): 379-82, 2011 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-21725206

RESUMO

A 64-y-old man presented to Medical Oncology Department a metastatic invasive ductal breast carcinoma, positive for estrogen (ER) and progesterone receptors (PR) and Her2/neu negative. The patient was treated with different lines of therapy, with rapid radiological progression of disease. After four courses of a third-line chemotherapy, a radiological stable disease was maintained. The patient was followed by serial blood drawings for the characterization and count of circulating tumor cells (CTC). This is the first report concerning the predictive and prognostic value of CTC in a male breast cancer patient.


Assuntos
Neoplasias da Mama Masculina/sangue , Neoplasias da Mama Masculina/tratamento farmacológico , Carcinoma Ductal de Mama/sangue , Carcinoma Ductal de Mama/tratamento farmacológico , Células Neoplásicas Circulantes/efeitos dos fármacos , Carboplatina/administração & dosagem , Carboplatina/farmacologia , Carboplatina/uso terapêutico , Contagem de Células , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacologia , Desoxicitidina/uso terapêutico , Docetaxel , Resistencia a Medicamentos Antineoplásicos , Epirubicina/administração & dosagem , Epirubicina/farmacologia , Epirubicina/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Receptor ErbB-2/biossíntese , Receptores de Estrogênio/biossíntese , Receptores de Progesterona/biossíntese , Taxoides/administração & dosagem , Taxoides/farmacologia , Taxoides/uso terapêutico , Gencitabina
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