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1.
Artigo em Inglês | MEDLINE | ID: mdl-34364814

RESUMO

BACKGROUND: A recent phase II randomized Japanese study reported better survival with regorafenib followed at progression by cetuximab ± irinotecan compared with the reverse standard sequence in chemo-refractory and anti-EGFR-naïve, RAS wild-type (wt) mCRC patients. Nowadays the use of anti-EGFR antibodies is more frequently anticipated to the first-line of therapy especially in patients with left-sided RAS/BRAF wt tumours. However, retrospective analyses and phase II single-arm trials showed promising activity of re-using anti-EGFRs in metastatic colorectal cancer (mCRC) patients who previously achieved benefit from a first-line anti-EGFR-based treatment. Post-hoc analyses of these trials revealed that the detection of RAS mutations in circulating tumour DNA (ct-DNA) at the time of re-treatment may be useful to identify resistant patients. PATIENTS AND METHODS: PARERE (NCT04787341) is a prospective, open label, multicentre phase II study in which 214 RAS/BRAF wt chemo-refractory mCRC patients with previous benefit from first-line anti-EGFR-based treatment and RAS/BRAF wt ct-DNA in the liquid biopsy collected at the time of inclusion will be randomized in a 1:1 ratio to receive panitumumab followed after progression by regorafenib versus the reverse sequence. Primary endpoint is overall survival. Secondary endpoints are 1st-progression free-survival (PFS), 2nd-PFS, time to failure strategy, objective response rate, and safety. AIM OF THE STUDY: The aim of this study is to validate the role of anti-EGFR retreatment and its proper placement in the therapeutic route of mCRC patients selected according to the analysis of ct-DNA in liquid biopsy. Results are expected at the end of 2023.

2.
Diagnostics (Basel) ; 11(1)2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33477676

RESUMO

We analyzed the clinical and pathological features of renal cell carcinoma (RCC) patients treated with cabozantinib stratified by body mass index (BMI). We retrospectively collected data from 16 worldwide centers involved in the treatment of RCC. Overall survival (OS) and progression-free survival (PFS) were analyzed using Kaplan-Meier curves. Cox proportional models were used at univariate and multivariate analyses. We collected data from 224 patients with advanced RCC receiving cabozantinib as second- (113, 5%) or third-line (111, 5%) therapy. The median PFS was significantly higher in patients with BMI ≥ 25 (9.9 vs. 7.6 months, p < 0.001). The median OS was higher in the BMI ≥ 25 subgroup (30.7 vs. 11.0 months, p = 0.003). As third-line therapy, both median PFS (9.2 months vs. 3.9 months, p = 0.029) and OS (39.4 months vs. 11.5 months, p = 0.039) were longer in patients with BMI ≥ 25. BMI was a significant predictor for both PFS and OS at multivariate analysis. We showed that a BMI ≥ 25 correlates with longer survival in patients receiving cabozantinib. BMI can be easily assessed and should be included in current prognostic criteria for advanced RCC.

3.
Cancers (Basel) ; 11(9)2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31443386

RESUMO

Background: In human populations, a certain amount of data correlate obesity/body mass index (BMI) with urothelial cancer (UC) and prostate cancer (PCa) occurrence, however this is not fully elucidated at all stages of disease. In an attempt to shed light on uncertain areas in such field, in the present review we illustrate the main molecular mechanisms linking obesity and cancer, focusing on the correlation between obesity and tumor risk, disease progression and response to chemo- and immunotherapy in patients with UC and the predictive/prognostic role of obesity in PCa patients treated with the currently available therapeutic approaches. Methods: We did a large-scale literature search on existing scientific websites focusing on keywords "obesity", "body mass index (BMI)", "urothelial cancer", "prostate cancer", "docetaxel", "cabazitaxel", "abiraterone acetate", "enzalutamide", and "radium223". Results: Many adipocytes-induced molecules support tumor proliferation through activation of various cellular pathways. The available evidence in the postoperative setting do the role of BMI in oncological outcomes prediction still not completely clear. Likewise, in metastatic UC patients controversial results link the role of obesity/BMI with clinical outcomes of tumor response to chemotherapy. Adipose stromal cells recruitment, induced by PCa cells, from white adipose tissue to the tumor sites inducing cell invasiveness was associated with poor survival. Conflicting data, although more oriented towards a better survival outcome, resulted in obese patients treated with docetaxel. In PCa cell-lines a certain cabazitaxel chemo resistance adipose stromal cells (ASC)-mediated was demonstrated. In metastatic castration-resistant PCa patients with high BMI (>25 kg/m2) receiving abiraterone acetate there were significant worse survival outcomes, while in enzalutamide patients BMI did not affect survival outcome. In radium 223 patients higher BMI significantly correlated with favorable overall survival. Conclusions: The main focus of this review was to understand the interplay between obesity/BMI and UC/PCa. Several pathogenic cellular pathways exploring the issue are discussed, opening the way to challenging tailored treatments on the basis of BMI. Improving the knowledge of molecular connections between obesity and UC and PCa could favor the development of new therapies likely reducing chemo- and immunotherapy drug resistance.

4.
Breast Cancer Res ; 21(1): 71, 2019 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-31142370

RESUMO

Currently, there is limited data regarding the effectiveness of standard subsequent line therapies such as endocrine therapy, chemotherapy, or targeted agents after progression on CDK4/6 inhibitor-based regimens. This paper describes time-to-treatment failure beyond progression on palbociclib or palbociclib+endocrine therapy in patients enrolled in the phase II, multicenter TREnd trial. Our results indicate that there is limited benefit from post-palbociclib treatment, regardless of the type of therapy received. A small population of long responders were identified who demonstrated ongoing benefit from a subsequent line of endocrine therapy after progression to palbociclib-based regimens. A translational research program is ongoing on this population of outliers.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Piperazinas/uso terapêutico , Piridinas/uso terapêutico , Antineoplásicos Hormonais/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/metabolismo , Feminino , Humanos , Estimativa de Kaplan-Meier , Piperazinas/administração & dosagem , Piperazinas/efeitos adversos , Pós-Menopausa , Prognóstico , Piridinas/administração & dosagem , Piridinas/efeitos adversos , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Resultado do Tratamento
5.
Eur J Cancer ; 110: 32-41, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30739838

RESUMO

BACKGROUND: Neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC) does not achieve effective control of distant metastases. Induction chemotherapy is a promising strategy, and bevacizumab (BV) could improve the results of CRT. 5-Fluorouracil, oxaliplatin and irinotecan (FOLFOXIRI) plus BV is a treatment option in metastatic colorectal cancer. We evaluate feasibility and efficacy of neoadjuvant treatment comprising induction FOLFOXIRI plus BV followed by CRT with fluoropyrimidines plus BV. METHODS: In this phase II single-arm trial, patients node-positive or clinical T4 or high-risk T3 LARC underwent 6 cycles of induction FOLFOXIRI plus BV, followed by CRT (50.4 Gy plus concomitant capecitabine) and BV (5 mg/kg on days 1, 15 and 28). Surgery was planned 8 weeks after completion of CRT. Primary end-point was 2-year disease-free survival (DFS). RESULTS: We enrolled 49 patients: All but one (withdrewing consent after enrolment) were included in the per-protocol analyses. The study met its primary end-point: 36 patients were free of recurrence at 2 years (2-y DFS: 80.45%, 95% confidence interval [CI]: 78.79-82.10). Forty-four patients underwent surgery; pathologic complete response rate was 36.4%. Forty-six patients completed induction: neutropenia (41.6%) and diarrhoea (12.5%) were main G3/4 toxicities. Forty-five patients received CRT, but the protocol was amended and the capecitabine schedule during CRT was slightly modified after 13 patients due to the incidence of G3 hand-foot syndrome and proctitis (23.1%). After amendment, no severe events during CRT were reported. CONCLUSIONS: FOLFOXIRI plus BV followed by CRT plus BV is feasible and active. Results in terms of DFS suggest that this strategy may improve distant disease control in LARC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Retais/terapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/administração & dosagem , Bevacizumab/efeitos adversos , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Camptotecina/análogos & derivados , Quimiorradioterapia/métodos , Quimiorradioterapia/mortalidade , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Terapia Neoadjuvante/mortalidade , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Neoplasias Retais/mortalidade , Resultado do Tratamento
6.
Cancers (Basel) ; 12(1)2019 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-31905816

RESUMO

Cabozantinib is approved for the treatment of renal cell carcinoma (RCC). However, prognostic factors are still lacking in this context. The aim of this study was to evaluate prognostic factors in RCC patients treated with second- or third-line cabozantinib. A multicenter retrospective real-world study was conducted, involving 32 worldwide centers. A total of 237 patients with histologically confirmed clear-cell and non-clear-cell RCC who received cabozantinib as second- or third-line therapy for metastatic disease were included. We analyzed overall survival (OS), progression-free survival (PFS) and time-to-strategy failure (TTSF) using Kaplan-Meier curves. Cox proportional models were used at univariate and multivariate analyses.The median PFS and OS of cabozantinib were 7.76 months (95% CI 6.51-10.88) and 11.57 months (95% CI 10.90-not reached (NR)) as second-line and 11.38 months (95% CI 5.79-NR) and NR (95% CI 11.51-NR) as third-line therapy. The median TTSF and OS were 11.57 and 15.52 months with the sequence of cabozantinib-nivolumab and 25.64 months and NR with nivolumab-cabozantinib, respectively. The difference between these two sequences was statistically significant only in good-risk patients. In the second-line setting, hemoglobin (Hb) levels (HR= 2.39; 95% CI 1.24-4.60, p = 0.009) and IMDC (International Metastatic Renal Cell Carcinoma Database Consortium) group (HR = 1.72, 95% CI 1.04-2.87, p = 0.037) were associated with PFS while ECOG-PS (HR = 2.33; 95%CI, 1.16-4.69, p = 0.018) and Hb levels (HR = 3.12; 95%CI 1.18-8.26, p = 0.023) correlated with OS at multivariate analysis, while in the third-line setting, only Hb levels (HR = 2.72; 95%CI 1.04-7.09, p = 0.042) were associated with OS. Results are limited by the retrospective nature of the study.This real-world study provides evidence on the presence of prognostic factors in RCC patients receiving cabozantinib.

7.
ESMO Open ; 3(4): e000403, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30018814

RESUMO

Background: FOLFOXIRI plus bevacizumab is considered a standard option in the upfront treatment of clinically selected patients with metastatic colorectal cancer irrespective of RAS and BRAF molecular status. The randomised MACBETH and VOLFI studies showed that a modified FOLFOXIRI regimen in combination with cetuximab or panitumumab, respectively, achieved high therapeutic activity in RAS and BRAF wild-type patients with an acceptable toxicity profile. Drawing from these considerations, we designed TRIPLETE study aiming at comparing two different chemotherapy backbones (mFOLFOXIRI or mFOLFOX6) in combination with panitumumab in the first-line treatment of patients with RAS and BRAF wild-type metastatic colorectal cancer. Methods: This is a prospective, open-label, multicentre phase III trial in which initially unresectable and previously untreated RAS and BRAF wild-type metastatic colorectal cancer patients are randomised to receive a standard treatment with mFOLFOX6 plus panitumumab or an experimental regimen with modified FOLFOXIRI (irinotecan 150 mg/m2, oxaliplatin 85 mg/m2, L-leucovorin 200 mg/m2, 5-fluoruracil 2400 mg/m2 48-hour continuous infusion) plus panitumumab up to 12 cycles, followed by panitumumab plus 5-fluorouracil and L-leucovorin until disease progression. The primary endpoint is overall response rate according to RECIST 1.1 criteria. Discussion: The relative benefit of chemotherapy intensification when using an anti-EGFR-based regimen in molecularly selected patients is unknown; TRIPLETE study aims at filling this gap of knowledge. The study is sponsored by the Gruppo Oncologico Nord Ovest Cooperative Group and is currently ongoing at 42 Italian centres. Clinical trial information: NCT03231722.

8.
Expert Opin Pharmacother ; 19(9): 1021-1025, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29851529

RESUMO

INTRODUCTION: Renal cell carcinoma (RCC) represents a heterogeneous group of cancers with distinct histological features, molecular alterations, prognosis, and response to therapy. Target agents directed against vascular endothelial growth factor and its receptor and mammalian target of rapamycin (mTOR) inhibitors have completely changed the landscape of RCC. However, the rate of complete response is still low, thus supporting the research of novel therapeutic agents. Area covered: The authors describe the chemical features of tivozanib, its pharmacodynamic and pharmacokinetic properties, and the results obtained in human phase I-III clinical trials. Tivozanib received its first global approval in EU, Iceland, and Norway on 28 August 2017 for the first-line treatment of adult patients with advanced RCC and for adult patients who are VEGFR and mTOR inhibitor-naive following disease progression after one prior treatment with cytokines. Expert opinion: The US Food and Drug Administration did not approve tivozanib due to the lack of a significant advantage in terms of survival compared to sorafenib. To date, the role of tivozanib in the pharmaceutical landscape of mRCC appears to be very limited. However, ongoing trials on the association between tivozanib and immunotherapy may represent a promising strategy to be assessed in future clinical trials.


Assuntos
Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Compostos de Fenilureia/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Quinolinas/uso terapêutico , Carcinoma de Células Renais/patologia , Ensaios Clínicos como Assunto , Meia-Vida , Humanos , Neoplasias Renais/patologia , Compostos de Fenilureia/química , Compostos de Fenilureia/farmacocinética , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacocinética , Quinolinas/química , Quinolinas/farmacocinética , Receptores de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Receptores de Fatores de Crescimento do Endotélio Vascular/metabolismo , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/metabolismo , Resultado do Tratamento
9.
Br J Cancer ; 116(3): 318-323, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-28081548

RESUMO

BACKGROUND: Different antiangiogenics are currently indicated in the second-line treatment of metastatic colorectal cancer (mCRC), following a first-line bevacizumab-containing treatment. The magnitude of benefit is limited, but no predictors of benefit have been identified. METHODS: A total of 184 mCRC patients progressing to a first-line bevacizumab-containing treatment were randomised in the BEBYP study to continue or not the antiangiogenic in combination with a second-line chemotherapy. A subgroup analysis according to baseline serum lactate dehydrogenase (LDH) levels was carried out. RESULTS: A significant interaction effect between LDH levels and treatment was found in terms of progression-free survival (PFS; P=0.002). Although patients with low LDH levels achieved significant PFS benefit from the continuation of bevacizumab (HR: 0.39 (95% CI: 0.23-0.65)), patients with high levels did not (HR: 1.10 (95% CI: 0.74-1.64)). Consistent results were reported in overall survival (OS; P=0.075). CONCLUSIONS: As preclinical evidence suggests that serum LDH may be a marker of tumour angiogenesis activation, low levels may indicate that bevacizumab is still efficacious in inhibiting angiogenesis. Validation of present results in subgroup analyses of other randomised trials of second-line angiogenesis inhibitors is warranted.


Assuntos
Adenocarcinoma/tratamento farmacológico , Inibidores da Angiogênese/uso terapêutico , Bevacizumab/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , L-Lactato Desidrogenase/sangue , Adenocarcinoma/patologia , Adulto , Idoso , Biomarcadores Tumorais/sangue , Quimioterapia Adjuvante , Neoplasias Colorretais/patologia , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Resultado do Tratamento
10.
Tumori ; 102(Suppl. 2)2016 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-26979247

RESUMO

PURPOSE: Secondary malignancies are new cancers occurring in patients previously treated with radiation or chemotherapy for a primary tumor. Secondary cancers are not related to the primary tumor, and may develop months or years after cancer treatment: they are usually a result of the first cancer therapy. Chemotherapy and radiotherapy may increase the risk of second cancers, such as skin tumors (basal or squamous cell carcinoma) or acute leukemia. METHODS: A patient with B-lymphoma and a patient with multiple myeloma, previously treated for breast cancer, are presented. RESULTS: We report the cases of 2 patients treated with adjuvant therapy for breast cancer who developed secondary bone marrow malignancies 15 years after primary treatment. CONCLUSIONS: By literature review, these 2 cases do not support the relationship between primary tumor treatment and secondary cancer, but strongly suggest the need for histologic samples when bone metastasis occurred after years from diagnosis of breast cancer. In this setting, the oncologist should take into account a secondary bone marrow tumor before starting treatment for breast cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Medula Óssea/etiologia , Neoplasias da Mama/tratamento farmacológico , Segunda Neoplasia Primária/etiologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Medula Óssea/diagnóstico , Neoplasias da Mama/diagnóstico , Quimioterapia Adjuvante , Feminino , Humanos , Linfoma de Células B/diagnóstico , Linfoma de Células B/tratamento farmacológico , Linfoma de Células B/etiologia , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/etiologia , Estadiamento de Neoplasias , Segunda Neoplasia Primária/diagnóstico , Resultado do Tratamento , Neoplasias de Mama Triplo Negativas/tratamento farmacológico
11.
Palliat Support Care ; 8(1): 41-8, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20163759

RESUMO

OBJECTIVE: Art therapy has been shown to be helpful to cancer patients at different stages in the course of their illness, especially during isolation for bone marrow transplantation, during radiotherapy treatment, and after treatment. The aim of this study is twofold: (1) to assess whether patients during chemotherapy sessions perceive art therapy as helpful and (2) to outline in which way art therapy is perceived as helpful. METHOD: 157 cancer patients attending an Oncology Day Hospital (Siena, Italy) met the art therapist during their chemotherapy sessions. The art therapist used the same art therapy technique with each patient during the first encounter ("free collage"); afterward the relationship would evolve in different ways according to the patients' needs. A psychologist interviewed a randomized group of 54 patients after the chemotherapy treatment using a semistructured questionnaire. RESULTS: Out of the 54 patients, 3 found art therapy "not helpful" ("childish," "just a chat," "not interesting"). The other 51 patients described their art therapy experience as "helpful." From patients' statements, three main groups emerged: (1) art therapy was perceived as generally helpful (e.g., "relaxing," "creative"; 37.3%), (2) art therapy was perceived as helpful because of the dyadic relationship (e.g., "talking about oneself and feeling listened to"; 33.3%), and (3) art therapy was perceived as helpful because of the triadic relationship, patient-image-art therapist (e.g., "expressing emotions and searching for meanings"; 29.4%). SIGNIFICANCE OF RESULTS: These data have clinical implications, as they show that art therapy may be useful to support patients during the stressful time of chemotherapy treatment. Different patients use it to fulfil their own different needs, whether it is a need to relax (improved mood) or to talk (self-narrative) or to visually express and elaborate emotions (discovering new meanings). Some illustrations of patients using the art therapy process to fulfill these three different needs are provided.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia pela Arte/métodos , Comportamento de Ajuda , Neoplasias/tratamento farmacológico , Neoplasias/psicologia , Relações Profissional-Paciente , Transtornos de Estresse Pós-Traumáticos/terapia , Adaptação Psicológica , Idoso , Atitude Frente a Saúde , Feminino , Humanos , Acontecimentos que Mudam a Vida , Masculino , Pessoa de Meia-Idade , Apoio Social , Transtornos de Estresse Pós-Traumáticos/etiologia , Transtornos de Estresse Pós-Traumáticos/psicologia , Inquéritos e Questionários
12.
Tumori ; 96(6): 875-88, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-21388048

RESUMO

AIMS AND BACKGROUND: Triple-negative breast cancer, defined by a lack of expression of estrogen, progesterone and HER-2 receptors, accounts for 15% of all types of breast cancer. The subtype mainly includes a molecularly distinct subgroup, the basal-like subtype (accounting for 75% of all cases). We attempt to define triple-negative breast cancer and compare it with basal-like disease, review the molecular, pathologic and clinical features of triple-negative disease, provide an overview of a retrospective subset analysis of clinical trials, and outline ongoing therapeutic trials and possible paths for future research. METHODS: We collected data regarding classification, molecular and clinical features and treatment, drawn from the existing literature, including abstracts and verbal accounts. By the term "basal-like", we defined all cases where gene expression array or more sophisticated immunophenotypes are used for identification. When the analysis is restricted to clinical assay (immunohistochemistry), we refer to "triple-negative". RESULTS: Basal-like breast cancer expresses genes characteristic of basal epithelial cells, which include high-molecular weight basal cytokeratins (CK5/6, CK14, CK17), vimentin, p-cadherin, alpha B crystalline, caveolins 1 and 2 and EGFR. The expression of basal markers (basal cytokeratins and EGFR) is related to a worse prognosis and identifies a clinically distinct subgroup within the triple-negative breast cancer. BRCA1 mutations are present in 11% of triple-negative tumors and even more rare is BRCA2 deficiency. BR-CA1-associated breast cancers types are typically characterized by a high rate of DNA aberrations and defective DNA repair pathways (the so-called "BRCAness"). The use of regimens based on DNA-damaging agents, such as anthracyclines, platinum derivatives and cyclophosphamide seems a sensible option for this breast cancer subtypes. Clinical data support a strong sensitivity to primary chemotherapy with pathologic response rates ranging from 27-45% (with anthracyclines and taxanes) to more than 60% with platinum-based triplets. However, based on retrospective data, major response to chemotherapy does not carry better survival ("triple-negative paradox"). There is no specific targeted therapy in the armamentarium: ongoing trials include anti-angiogenic agents, anti-EGFR and EGFR-TK inhibitors, epothilones and PARP inhibitors. CONCLUSIONS: A specific systemic regimen cannot yet be recommended. Moreover, only a few data are available on which treatment selection can be based. Use of the existing cytotoxic agents can be optimized for this patient subgroup by investigating the proliferative signals and the suitability of these signals as therapeutic targets, besides assessing the BRCA1-pathway in this subgroup as regards treatment. A greater understanding of the pathologic and molecular characteristics of this phenotype may lead to customized treatment for these patients.


Assuntos
Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Inibidores da Angiogênese/uso terapêutico , Antineoplásicos/farmacologia , Neoplasias da Mama/classificação , Neoplasias da Mama/tratamento farmacológico , Caveolina 1/metabolismo , Ensaios Clínicos como Assunto , Dano ao DNA , Reparo do DNA/genética , Receptores ErbB/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Genes BRCA1 , Genes src , Humanos , Imuno-Histoquímica , Imunofenotipagem , Mutação , Proteínas Proto-Oncogênicas c-kit/metabolismo , Proteína Supressora de Tumor p53/metabolismo
13.
Cancer ; 110(4): 752-8, 2007 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-17594712

RESUMO

BACKGROUND: Gefitinib, an orally active inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, combined with chemotherapy, has shown efficacy as second-line treatment for advanced colorectal cancer (CRC). Gefitinib combined with FOLFOX6 (oxaliplatin plus folinic acid and 5-fluorouracil) was tested as a first-line therapy. METHODS: Patients with metastatic EGFR-positive CRC received gefitinib at a dose of 250 mg/day combined with simplified FOLFOX6. Gefitinib was continued as maintenance treatment in nonprogressing patients. Responses were assessed by Response Evaluation Criteria in Solid Tumors (RECIST) criteria and adverse events were assessed with the National Cancer Institute Common Toxicity Criteria (NCI-CTC) scale. RESULTS: A total of 56 patients were recruited. There were 26 men and 30 women, with a median age of 57.5 years. The Eastern Cooperative Oncology Group (ECOG) performance status was as follows: 0 in 39 patients, 1 in 12 patients, and 2 in 5 patients. Thirty-nine patients (69.6%) had stage IV disease at diagnosis, 92.9% had liver involvement, and 46.4% had > or =2 metastatic sites. All patients were evaluated for safety, and 53 were evaluated for response: 40 patients (71.4%; 95% confidence interval [95% CI], 57.8%-82.6%) had complete or partial responses, and 11 patients (19.6%) had stable disease. Median time to progression was 7 months (range, 2.1-33.0 months; 95% CI, 6.2-9.0 months). Radical surgery or thermoablation of metastatic sites was performed in 14 patients (25%). NCI-CTC grade 3-4 events occurred in 36 patients (64.3%): diarrhea in 9 patients (16.1%), and hematologic toxicity in 13 patients (23.2%). Four patients (7.1%) were withdrawn for drug-related adverse events. CONCLUSIONS: The regimen has shown promising efficacy with manageable toxicity as a first-line treatment for patients with advanced CRC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Receptores ErbB/antagonistas & inibidores , Administração Oral , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Diarreia/induzido quimicamente , Progressão da Doença , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Gefitinibe , Humanos , Estimativa de Kaplan-Meier , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Neutropenia/induzido quimicamente , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Oxaliplatina , Pacientes Desistentes do Tratamento/estatística & dados numéricos , Quinazolinas/administração & dosagem , Quinazolinas/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
14.
Int J Cancer ; 106(4): 534-544, 2003 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-12845649

RESUMO

Screening cDNA libraries from solid human tumors with sera of autologous patients (SEREX) has proven to be a powerful approach to identifying tumor antigens recognized by the humoral arm of the immune system. In many cases, application of this methodology has led to the discovery of novel tumor antigens as unknown gene products. We tried to improve the potency of the SEREX approach by combining it with phage-display technology. We designed a new lambda vector to express protein fragments as N-terminal fusions to the D capsid protein and generated high-complexity cDNA libraries from human breast carcinoma cell lines and solid tumors. Screening these phage-displayed libraries required limited amounts of sera from patients and efficiently identified several tumor antigens specifically reacting with sera from breast cancer patients.


Assuntos
Antígenos de Neoplasias/análise , Neoplasias da Mama/imunologia , DNA de Neoplasias/imunologia , Biblioteca Gênica , Adulto , Idoso , Animais , Anticorpos Antineoplásicos/sangue , Bacteriófago M13/genética , Bacteriófago lambda , Western Blotting , Neoplasias da Mama/genética , Clonagem Molecular , Primers do DNA/química , Feminino , Citometria de Fluxo , Vetores Genéticos , Glutationa Transferase/metabolismo , Humanos , Immunoblotting , Masculino , Programas de Rastreamento , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , RNA Mensageiro/biossíntese , Transfecção , Células Tumorais Cultivadas
15.
Am J Clin Oncol ; 25(3): 224-6, 2002 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12040276

RESUMO

At present, no effective therapy is available for hepatocellular carcinoma, when local treatments have failed. We reported the results obtained with prolonged, ultra-low-dose (1 MIU/d until progression), subcutaneous interleukin-2 (IL-2) in a series of 18 consecutive patients (14 men and 4 women, median age 66 years, range 49-82 years) with advanced, histologically proven HCC on liver cirrhosis. During a median follow-up time of 19.5 months, two complete responses (11.1%), lasting 35 and 46 months, respectively, and one partial response (5.5%) were recorded (overall response rate: 16.6%; 95% CI: 0-33.8%). Thirteen patients (72.3%; 95% CI: 61.6-82.7) had stable disease lasting at least 4 months; 1 of these patients obtained a complete response on lung metastases. Median time to progression was 15.3 months (95% CI: 10-33). Median overall survival was 24.5 months (95% CI: 12-43). Two patients (11.1%) progressed during therapy. Toxicity was only local (usually pain and pomphus in the site of injection). Low-dose IL-2 can be considered an active and well-tolerated treatment for unresectable hepatocellular carcinoma. Future studies on large numbers of patients are necessary to confirm these results.


Assuntos
Antineoplásicos/administração & dosagem , Carcinoma Hepatocelular/tratamento farmacológico , Interleucina-2/administração & dosagem , Neoplasias Hepáticas/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Feminino , Humanos , Injeções Subcutâneas , Interleucina-2/uso terapêutico , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Terapia de Salvação , Análise de Sobrevida
16.
Anticancer Res ; 22(2A): 727-32, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12014643

RESUMO

BACKGROUND: Chronic subcutaneous rIL-2 at low doses produces long-lasting immunomodulatory effects and is considered an effective treatment for renal cell carcinoma with marginal activity in malignant melanoma and colorectal cancer. PATIENTS AND METHODS: In this study we evaluated, by Minnesota Multiphasic Personality Inventory (MMPI), the psychological changes induced by rIL-2 in 10 patients with advanced tumors. RESULTS: After 3 months of rIL-2 treatment, 80% of the patients had a significantly increased score on the clinical scale of depression (D) and psychasthenia (Pt) (p<0.01), 70% on the scale of conversion hysteria (Hy) and 60% on the scales of schizophrenia (Sc) and psychopathic deviate (Pd), (p<0.05). These MMPI changes were however not paralleled by disease progression or clinical-overt psychological disease. CONCLUSION: These findings demonstrate that low-dose rIL-2 is a psychoactive treatment, which deserves psychological monitoring The MMPI is feasible for the evaluation of subclinical psychological modifications induced by cytokine immunotherapy.


Assuntos
Antineoplásicos/efeitos adversos , Interleucina-2/efeitos adversos , Transtornos da Personalidade/induzido quimicamente , Adulto , Idoso , Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/psicologia , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/psicologia , Relação Dose-Resposta a Droga , Feminino , Humanos , Injeções Subcutâneas , Interleucina-2/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/psicologia , MMPI , Masculino , Melanoma/tratamento farmacológico , Melanoma/psicologia , Pessoa de Meia-Idade , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico
17.
Cancer ; 94(5): 1414-20, 2002 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-11920496

RESUMO

BACKGROUND: Therapeutic options to cure advanced, recurrent, and metastatic thymic tumors are limited. Evidence of a high uptake of indium-labeled octreotide ((111)In-DTPA-D-Phe(1)-octreotide) in thymic tumors and the curative application of somatostatin analogs and prednisone in one patient with thymoma and pure red cell aplasia led the authors to start a Phase II study. METHODS: Sixteen patients with advanced thymic tumors, unresponsive to conventional chemotherapeutic regimens, were enrolled in the study. The schedule includes administration of somatostatin analog octreotide (1.5 mg/day subcutaneously) associated with prednisone (0.6 mg/kg/day orally for 3 months, 0.2 mg/kg/day orally during follow-up). In 8 cases, octreotide was replaced by the long-acting analog lanreotide (30 mg/every 14 days intramuscolarly). Treatment was prolonged until progression of disease was documented. Overall response rate, survival, progression free survival, and toxicity were evaluated. RESULTS: The overall response rate among 16 evaluable patients was 37%. One patient (6%) had a complete response, 5 (31%) had a partial response, 6 obtained a stabilization of disease, and 4 progressed during the treatment. After a median follow-up of 43 months, the median survival was 15 months, and median time to progression was 14 months. Treatment was generally well tolerated with acceptable toxicity: cholelithiasis (1 patient), Grade 2 cushingoid appearance (3 patients), Grade 1 diarrhea (5 patients), Grade 2 hyperglycemia (3 patients). CONCLUSIONS: Treatment with somatostatin analogs and prednisone has shown efficacy in patients with recurrent and metastatic malignant thymic tumors refractory to standard therapeutic options. The results obtained are very satisfactory given the lack of effective alternative treatments. Such therapy is not burdened by the same toxicity of chemotherapy; thus, it can be administered to heavily pretreated patients. Somatostatin analogs and prednisone are well tolerated, and the long-acting analog lanreotide, which requires fewer injections, improves patients' compliance.


Assuntos
Antineoplásicos Hormonais/farmacologia , Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Octreotida/farmacologia , Peptídeos Cíclicos/farmacologia , Prednisona/farmacologia , Somatostatina/farmacologia , Neoplasias do Timo/tratamento farmacológico , Administração Oral , Adulto , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/efeitos adversos , Feminino , Humanos , Injeções Intramusculares , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Octreotida/administração & dosagem , Octreotida/efeitos adversos , Cooperação do Paciente , Peptídeos Cíclicos/administração & dosagem , Peptídeos Cíclicos/efeitos adversos , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Somatostatina/administração & dosagem , Somatostatina/efeitos adversos , Somatostatina/análogos & derivados , Análise de Sobrevida , Neoplasias do Timo/patologia , Resultado do Tratamento
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