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1.
Ann Oncol ; 35(6): 549-558, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38423389

RESUMO

BACKGROUND: 18F-fluoroestradiol (FES) positron emission tomography (PET)/computed tomography (CT) is considered an accurate diagnostic tool to determine whole-body endocrine responsiveness. In the endocrine therapy (ET)-FES trial, we evaluated 18F-FES PET/CT as a predictive tool in estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC). PATIENTS AND METHODS: Eligible patients underwent an 18F-FES PET/CT at baseline. Patients with standardized uptake value (SUV) ≥ 2 received single-agent ET until progressive disease; patients with SUV < 2 were randomized to single-agent ET (arm A) or chemotherapy (ChT) (arm B). The primary objective was to compare the activity of first-line ET versus ChT in patients with 18F-FES SUV < 2. RESULTS: Overall, 147 patients were enrolled; 117 presented with 18F-FES SUV ≥ 2 and received ET; 30 patients with SUV < 2 were randomized to ET or ChT. After a median follow-up of 62.4 months, 104 patients (73.2%) had disease progression and 53 died (37.3%). Median progression-free survival (PFS) was 12.4 months [95% confidence interval (CI) 3.1-59.6 months] in patients with SUV < 2 randomized to arm A versus 23.0 months (95% CI 7.7-30.0 months) in arm B, [hazard (HR) = 0.71, 95% CI 0.3-1.7 months]; median PFS was 18.0 months (95% CI 11.2-23.1 months) in patients with SUV ≥ 2 treated with ET. Median overall survival (OS) was 28.2 months (95% CI 14.2 months-not estimable) in patients with SUV < 2 randomized to ET (arm A) versus 52.8 months (95% CI 16.2 months-not estimable) in arm B (ChT). Median OS was not reached in patients with SUV ≥ 2. 60-month OS rate was 41.6% (95% CI 10.4% to 71.1%) in arm A, 42.0% (95% CI 14.0% to 68.2%) in arm B, and 59.6% (95% CI 48.6% to 69.0%) in patients with SUV ≥ 2. In patients with SUV ≥ 2, 60-month OS rate was 72.6% if treated with aromatase inhibitors (AIs) versus 40.6% in case of fulvestrant or tamoxifen (P < 0.005). CONCLUSIONS: The ET-FES trial demonstrated that ER+/HER2- MBC patients are a heterogeneous population, with different levels of endocrine responsiveness based on 18F-FES CT/PET SUV.


Assuntos
Neoplasias da Mama , Estradiol , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Receptor ErbB-2 , Receptores de Estrogênio , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/mortalidade , Pessoa de Meia-Idade , Projetos Piloto , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Receptores de Estrogênio/metabolismo , Estradiol/análogos & derivados , Idoso , Receptor ErbB-2/metabolismo , Adulto , Antineoplásicos Hormonais/uso terapêutico , Compostos Radiofarmacêuticos , Prognóstico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
2.
ESMO Open ; 8(5): 101824, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37774508

RESUMO

BACKGROUND: This study investigated the efficacy of chemoradiotherapy (CRT) followed by durvalumab as neoadjuvant therapy of locally advanced rectal cancer. PATIENTS AND METHODS: The PANDORA trial is a prospective, phase II, open-label, single-arm, multicenter study aimed at evaluating the efficacy and safety of preoperative treatment with durvalumab (1500 mg every 4 weeks for three administrations) following long-course radiotherapy (RT) plus concomitant capecitabine (5040 cGy RT in 25-28 fractions over 5 weeks and capecitabine administered at 825 mg/m2 twice daily). The primary endpoint was the pathological complete response (pCR) rate; secondary endpoints were the proportion of clinical complete remissions and safety. The sample size was estimated assuming a null pCR proportion of 0.15 and an alternative pCR proportion of 0.30 (α = 0.05, power = 0.80). The proposed treatment could be considered promising if ≥13 pCRs were observed in 55 patients (EudraCT: 2018-004758-39; NCT04083365). RESULTS: Between November 2019 and August 2021, 60 patients were accrued, of which 55 were assessable for the study's objectives. Two patients experienced disease progression during treatment. Nineteen out of 55 eligible patients achieved a pCR (34.5%, 95% confidence interval 22.2% to 48.6%). Regarding toxicity related to durvalumab, grade 3 adverse events (AEs) occurred in four patients (7.3%) (diarrhea, skin toxicity, transaminase increase, lipase increase, and pancolitis). Grade 4 toxicity was not observed. In 20 patients (36.4%), grade 1-2 AEs related to durvalumab were observed. The most common were endocrine toxicity (hyper/hypothyroidism), dermatologic toxicity (skin rash), and gastrointestinal toxicity (transaminase increase, nausea, diarrhea, constipation). CONCLUSION: This study met its primary endpoint showing that CRT followed by durvalumab could increase pCR with a safe toxicity profile. This combination is a promising, feasible strategy worthy of further investigation.


Assuntos
Terapia Neoadjuvante , Neoplasias Retais , Humanos , Capecitabina/farmacologia , Capecitabina/uso terapêutico , Estudos Prospectivos , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/patologia , Quimiorradioterapia/efeitos adversos , Diarreia/induzido quimicamente , Transaminases/uso terapêutico
3.
Breast Cancer Res Treat ; 174(2): 433-442, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30536182

RESUMO

PURPOSE: To investigate the efficacy of metformin (M) plus chemotherapy versus chemotherapy alone in metastatic breast cancer (MBC). METHODS: Non-diabetic women with HER2-negative MBC were randomized to receive non-pegylated liposomal doxorubicin (NPLD) 60 mg/m2 + cyclophosphamide (C) 600 mg/m2 × 8 cycles Q21 days plus M 2000 mg/day (arm A) versus NPLD/C (arm B). The primary endpoint was progression-free survival (PFS). RESULTS: One-hundred-twenty-two patients were evaluable for PFS. At a median follow-up of 39.6 months (interquartile range [IQR] 24.6-50.7 months), 112 PFS events and 71 deaths have been registered. Median PFS was 9.4 months (95% CI 7.8-10.4) in arm A and 9.9 (95% CI 7.4-11.5) in arm B (P = 0.651). In patients with HOMA index < 2.5, median PFS was 10.4 months (95% CI 9.6-11.7) versus 8.5 (95% CI 5.8-9.7) in those with HOMA index ≥ 2.5 (P = 0.034). Grade 3/4 neutropenia was the most common toxicity, occurring in 54.4% of arm A patients and 72.3% of the arm B group (P = 0.019). M induced diarrhea (G2) was observed in 8.8% of patients in Arm A. The effect of M was similar in patients with HOMA index < 2.5 and ≥ 2.5, for PFS and OS. CONCLUSIONS: The MYME trial failed to provide evidence in support of an anticancer activity of M in combination with first line CT in MBC. A significantly shorter PFS was observed in insulin-resistant patients (HOMA ≥ 2.5). Noteworthy, M had a significant effect on CT induced severe neutropenia. Further development of M in combination with CT in the setting of MBC is not warranted.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Metformina/administração & dosagem , Receptor ErbB-2/deficiência , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Ciclofosfamida/efeitos adversos , Doxorrubicina/efeitos adversos , Esquema de Medicação , Tratamento Farmacológico , Feminino , Humanos , Metformina/efeitos adversos , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Análise de Sobrevida , Resultado do Tratamento
4.
Epidemiol Infect ; 146(12): 1572-1574, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29843844

RESUMO

Common childhood infectious diseases have been associated with a reduced risk of following haematopoietic malignancies, but investigations on multiple myeloma (MM) are scarce. Information about 213 MM cases and 1128 healthy controls were obtained from a multicentre population-based Italian case-control study. The association between chickenpox, measles, mumps, pertussis and rubella and the MM risk was estimated by unconditional logistic regression, adjusting for age, gender and residence area. No association was found between MM risk and any considered infectious disease. The number of infections was slightly inversely associated with the risk of MM, but statistical significance was not reached (OR 0.87, 95% CI 0.55-1.4 for 1-2 diseases vs. none and OR 0.68, 95% CI 0.41-1.1 for 3-5 diseases, respectively, P = 0.131). We did not find a clear evidence that common infections during childhood are associated with the subsequent risk of developing MM.


Assuntos
Mieloma Múltiplo/epidemiologia , Mieloma Múltiplo/etiologia , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Causalidade , Varicela/epidemiologia , Criança , Feminino , Humanos , Itália/epidemiologia , Masculino , Sarampo/epidemiologia , Pessoa de Meia-Idade , Modelos Estatísticos , Caxumba/epidemiologia , Fatores de Risco , Rubéola (Sarampo Alemão)/epidemiologia , Coqueluche/epidemiologia
5.
Breast ; 29: 55-61, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27428471

RESUMO

BACKGROUND: Histological status of axillary lymph nodes is an important prognostic factor in patients receiving surgery for breast cancer (BC). Sentinel lymph node (SLN) biopsy (B) has rapidly replaced axillary lymph node dissection (ALND), and is now the standard of care for axillary staging in patients with clinically node-negative (N0) operable BC. The aim of this study is to compare pretreatment lymphoscintigraphy with a post primary systemic treatment (PST) scan in order to reduce the false-negative rates for SLNB. METHODS: In this single-institution study we considered 170 consecutive T2-4 N0-1 M0 BC patients treated with anthracycline-based PST. At the time of incisional biopsy, we performed sentinel lymphatic mapping. After PST, all patients repeated lymphoscintigraphy with the same methodology. During definitive surgery we performed further sentinel lymphatic mapping, SLNB and ALND. RESULTS: The SLN was removed in 158/170 patients giving an identification rate of 92.9% (95% confidence interval (CI) = 88.0-96.3%) and a false-negative rate of 14.0% (95% CI = 6.3-25.8%). SLNB revealed a sensitivity of 86.0% (95% CI = 74.2-93.7%), an accuracy of 94.9% (95% CI = 90.3-97.8%) and a negative predictive value of 92.7% (95% CI = 86.1-96.8%). CONCLUSION: Identification rate, sensitivity and accuracy are in accordance with other studies on SLNB after PST, even after clinically negative node conversion following PST. This study confirms that diagnostic biopsy and neoadjuvant chemotherapy maintain breast lymphatic drainage unaltered.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Linfocintigrafia/métodos , Linfonodo Sentinela/diagnóstico por imagem , Adulto , Idoso , Antraciclinas/uso terapêutico , Antibióticos Antineoplásicos/uso terapêutico , Axila , Neoplasias da Mama/terapia , Reações Falso-Negativas , Feminino , Humanos , Excisão de Linfonodo , Pessoa de Meia-Idade , Terapia Neoadjuvante , Valor Preditivo dos Testes , Linfonodo Sentinela/patologia , Linfonodo Sentinela/cirurgia , Biópsia de Linfonodo Sentinela
6.
Ann Oncol ; 26(6): 1201-1207, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25735317

RESUMO

BACKGROUND: We report the results from a first-line phase III randomized clinical trial on metastatic colorectal cancer (mCRC) aimed at evaluating the effectiveness of adding bevacizumab (B) to standard first-line chemotherapy (CT). PATIENTS AND METHODS: mCRC patients were randomized to receive first-line CT (FOLFIRI or FOLFOX4) plus B (arm A) or CT only (arm B). The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), response rate (ORR) and safety. Three hundred and fifty patients and 310 events were required to have an 80% statistical power to detect a difference in PFS between the groups. RESULTS: Between November 2007 and March 2012, 376 patients were randomized. About 60% of patients received FOLFOX4 and 40% FOLFIRI. After a median follow-up of 36 months, 343 progressions and 275 deaths had been observed in the overall population. The median PFS was 9.6 [95% confidence interval (CI) 8.2-10.3] and 8.4 (95% CI 7.2-9.0) months for arms A and B, respectively, with a hazard ratio of 0.86 (95% CI 0.70-1.07; P = 0.182). No statistically significant differences in OS or ORR were observed. B-containing regimens were associated with more frequent hypertension, bleeding, proteinuria and asthenia. CONCLUSIONS: The addition of B to standard first-line CT for mCRC did not provide a benefit in terms of PFS, OS or ORR. Further research is warranted to better identify the target population. CLINICAL TRIAL NUMBER: NCT01878422.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Camptotecina/análogos & derivados , Neoplasias Colorretais/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/efeitos adversos , Camptotecina/efeitos adversos , Camptotecina/uso terapêutico , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Progressão da Doença , Intervalo Livre de Doença , Feminino , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Humanos , Itália , Estimativa de Kaplan-Meier , Leucovorina/efeitos adversos , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Compostos Organoplatínicos/efeitos adversos , Compostos Organoplatínicos/uso terapêutico , Modelos de Riscos Proporcionais , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
7.
Breast Cancer Res Treat ; 145(1): 177-83, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24658893

RESUMO

Information on hormone receptor and human epidermal growth factor receptor-2 (HER2) expression in breast cancer is acknowledged as mandatory for prognostic stratification and treatment planning. Data on the biological features of African breast cancers are poor. We decided to compare histopathological and biomolecular characteristics (estrogen and progesterone receptor­ER, PgR, and HER2) of Tanzanian and Italian breast cancers. Differences in proliferating index and androgen receptor (AR) expression in triple-negative patients from the two case series were also assessed. Of the 103 consecutive patients seen at the Bugando Medical Center (Mwanza, Tanzania) from 2003 to 2010, who underwent biopsy or surgical resection of primary breast cancer, 69 patients had tissue samples that were evaluable for estrogen receptor (ER), progesterone receptor (PgR), and HER2. Histopathological assessment and biomolecular determinations were performed at the Cancer Institute of Romagna (IRST IRCCS, Meldola, Italy). Caucasian breast cancers were randomly extracted from an electronic database and matched (1:2 ratio) for year of diagnosis and age at diagnosis. Median age of both populations was 51 years (range 27­84). With respect to Caucasian tumors, Tanzanian breast cancers at diagnosis more frequently showed high histological grade (mainly grade 3) (P = 0.03), advanced clinical stage (III or IV) (P\0.001), ER negativity (52.2 %, P\0.001) and high proliferation (P = 0.0002). Triple-negative tumors were over-represented in Tanzanian women. AR was positive in 38.5 and 38 %of triple-negative Tanzanian and Italian breast cancers, respectively. Our results show that histopathological and biomolecular characteristics in Tanzanian and Italian breast cancers differ substantially. The high frequency of poorly differentiated, ER-negative, highly proliferating tumors, together with advanced stage at presentation, could be considered as the main prognostic factors linked to the high mortality rates for breast cancer in the African population.


Assuntos
Neoplasias da Mama/etnologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , População Negra , Estudos de Casos e Controles , Feminino , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Itália , Pessoa de Meia-Idade , Tanzânia , População Branca
8.
Minerva Anestesiol ; 80(8): 877-84, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24280812

RESUMO

BACKGROUND: Obstructive sleep apnea (OSA) is a common disease which increases the risk of perioperative complications. The aim of this study is to assess the clinical utility of preoperative screening for OSA in determining the prevalence of patients at high risk of OSA in a surgical population, the incidence of difficult airway management and the incidence of perioperative complications. METHODS: We conducted a multisite, prospective observational study on adult patients scheduled for elective surgery. All patients completed a STOP-Bang questionnaire as a part of their preoperative evaluation. Collected data included: demographic data, type of surgery, ASA class, postoperative course, complications within 48 hours, difficult intubation (DI) and difficult mask ventilation (DMV) rates. RESULTS: A total of 3452 consecutive patients were recruited; 2997 (87%) were identified as low OSA risk patients and 455 (13%) were identified as high OSA risk patients; 113 (3%) postoperative complications, 315 (9%) cases of DMV and 375 (11%) of DI were observed. The percentage of postoperative complications in patients with HR-OSA was 9%, while the percentage of DI was 20% and the percentage of DMV was 23%. High risk for OSA and higher BMI (≥30 Kg m-2) were independently associated with risk for perioperative complications. CONCLUSION: In conclusion, this study demonstrates that the prevalence of high OSA risk patients in the surgical population is high. The increase in the rates of perioperative complications justifies the implementation of perioperative strategies that use the STOP-Bang as a tool for triage.


Assuntos
Procedimentos Cirúrgicos Eletivos/métodos , Cuidados Pré-Operatórios/métodos , Apneia Obstrutiva do Sono/diagnóstico , Inquéritos e Questionários , Idoso , Procedimentos Cirúrgicos Eletivos/normas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/mortalidade , Estudos Prospectivos , Respiração Artificial/efeitos adversos , Respiração Artificial/métodos , Apneia Obstrutiva do Sono/epidemiologia , Apneia Obstrutiva do Sono/terapia
9.
Eur J Cancer ; 47(14): 2091-8, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21665463

RESUMO

AIM: To assess the activity and safety of non-pegylated liposomal doxorubicin (Myocet®) in combination with docetaxel and trastuzumab as first-line treatment of patients with HER-2/neu-positive metastatic breast cancer (MBC). PATIENTS AND METHODS: The maximum tolerated dose of the combination was defined in the phase I part of the study. In the phase II part, 45 HER-2/neu-positive MBC patients were enrolled to receive 6-8 cycles of Myocet® 50 mg/m2 (day 1), docetaxel 30 mg/m2 (days 2 and 9) plus trastuzumab (day 2, 4 mg/kg followed by 2 mg/kg/week) every 21 d until unacceptable toxicity or progression occurred. Objective response (primary end-point) and treatment tolerability were assessed according to World Health Organisation criteria. Cardiotoxicity was defined as signs and/or symptoms of congestive heart failure and/or a decrease in left ventricular ejection fraction (LVEF). RESULTS: The overall response rate was 55.6% (complete response 8.9%, partial response 46.7%), with a median time-to-progression of 10.9 months (C.I. 8.7-15.0). Median overall survival was not reached. The most frequent grade 3-4 adverse events were granulocytopaenia (60.0%), leukocytopenia (43.2%) and alopecia (35.6%). Grade 3-4 diarrhoea, pain, oral and skin toxicity (4.4%, each) and nausea/vomiting, thrombocytopenia and elevated alkaline phosphatase (2.2%, each) were also reported. In 2 patients LVEF fell to <50%, with a decrease from baseline>15%. LVEF median values remained stable from baseline to the end of the study (60%). CONCLUSIONS: The combination of Myocet®, docetaxel and trastuzumab is safe and shows promising activity as first-line treatment of HER-2-positive MBC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Insuficiência Cardíaca/induzido quimicamente , Adulto , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Docetaxel , Relação Dose-Resposta a Droga , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Doxorrubicina/análogos & derivados , Esquema de Medicação , Feminino , Insuficiência Cardíaca/prevenção & controle , Humanos , Lipossomos , Dose Máxima Tolerável , Pessoa de Meia-Idade , Metástase Neoplásica , Receptor ErbB-2/metabolismo , Taxoides/administração & dosagem , Taxoides/efeitos adversos , Trastuzumab , Resultado do Tratamento
10.
Ann Oncol ; 20(7): 1163-9, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19542532

RESUMO

BACKGROUND: Palliative sedation therapy (PST) is indicated for and used to control refractory symptoms in cancer patients undergoing palliative care. We aimed to evaluate whether PST has a detrimental effect on survival in terminally ill patients. METHODS: This multicenter, observational, prospective, nonrandomized population-based study evaluated overall survival in two cohorts of hospice patients, one submitted to palliative sedation (A) and the other managed as per routine hospice practice (B). Cohorts were matched for age class, gender, reason for hospice admission, and Karnofsky performance status. RESULTS: Of the 518 patients enrolled, 267 formed cohort A and 251 cohort B. In total, 25.1% of patients admitted to the participating hospices received PST. Mean and median duration of sedation was 4 (standard deviation 6.0) and 2 days (range 0-43), respectively. Median survival of arm A was 12 days [90% confidence interval (CI) 10-14], while that of arm B was 9 days (90% CI 8-10) (log rank = 0.95, P = 0.330) (unadjusted hazard ratio = 0.92, 90% CI 0.80-1.06). CONCLUSION: PST does not shorten life when used to relieve refractory symptoms and does not need the doctrine of double effect to justify its use from an ethical point of view.


Assuntos
Hipnóticos e Sedativos/uso terapêutico , Cuidados Paliativos/métodos , Estresse Psicológico/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Hospitais para Doentes Terminais , Humanos , Estimativa de Kaplan-Meier , Avaliação de Estado de Karnofsky , Tábuas de Vida , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Neoplasias/terapia , Estudos Prospectivos , Análise de Regressão , Assistência Terminal , Resultado do Tratamento , Adulto Jovem
11.
J Chemother ; 20(3): 374-9, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18606595

RESUMO

We carried out a multicentric retrospective study on cetuximab + chemotherapy in pre-treated refractory patients outside clinical protocols, by registering the main clinical and pathological parameters. We evaluated 144 pre-treated patients. Cetuximab was administered usually in combination with irinotecan (93.8%). A 45% disease control rate (complete plus partial responses plus stable disease) was obtained in 55 patients and was related to absence of weight loss (p<0.0001) and high grade (> or =2) skin toxicity (p<0.0001). Median time to progression (TTP) was 4 months (95%CI 2.7-5.3) and median overall survival (OS) was 11.8 months (95%CI 8.5-15.1). Performance status << or =1, no weight loss and high grade (>or =22) skin toxicity were related both to a longer TTP (p=0.035, p=0.035, p=0.0017) and OS (p<0.0001, p<0.0001, p=0.006). According to multivariate analysis, the absence of weight loss was related to longer TTP (HR 0.331, p=0.004) and OS (HR 0.176, p<0.0001), and EGFR over-expression (3+) to longer TTP (HR 0.402, p=0.020).


Assuntos
Anticorpos Monoclonais/administração & dosagem , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Colorretais/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Camptotecina/análogos & derivados , Cetuximab , Neoplasias Colorretais/mortalidade , Progressão da Doença , Feminino , Humanos , Irinotecano , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos , Pele/efeitos dos fármacos , Dermatopatias/induzido quimicamente , Redução de Peso
12.
Oncology ; 72(1-2): 118-24, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-18004083

RESUMO

OBJECTIVE: Taxanes and fluoropyrimidines are active in metastatic breast cancer (MBC), and their combination has proven effective in anthracycline-refractory patients. We conducted a phase I study to determine the maximum tolerated dose (MTD) of uracil plus tegafur (UFT) given in combination with leucovorin (LV) and paclitaxel (Pacl) in patients with refractory MBC. METHODS: Pacl was infused at a fixed dose of 150 mg/m2 on day 1. UFT, at doses escalated by 50 mg/m2 starting from 200 mg/m2 . day, and LV, at a fixed dose of 90 mg/day, were given orally every 8 h for 11 days (days 3-13). Cohorts of at least 3 patients were treated at each dose level, and if 1 experienced dose-limiting toxicity (DLT), a maximum of 3 additional patients were added at the same dose level. MTD was reached if 2 out of the 6 patients experienced DLT. RESULTS: Sixteen patients were enrolled in the study. The most important toxicity observed was hematological. Nonhematological toxicities were paresthesia and myalgia, asthenia, nausea, and mucositis. DLT occurred in only 1 patient (grade 3 hepatic toxicity). CONCLUSIONS: The recommended dose for a subsequent phase II trial is Pacl 150 mg/m2 on day 1, and UFT 300 mg/m2 and LV 90 mg on days 3-13, every 2 weeks.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Esquema de Medicação , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Leucovorina/administração & dosagem , Dose Máxima Tolerável , Pessoa de Meia-Idade , Modelos Teóricos , Metástase Neoplásica , Paclitaxel/administração & dosagem , Tegafur/administração & dosagem , Uracila/administração & dosagem
13.
Br J Cancer ; 97(11): 1499-504, 2007 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-17987035

RESUMO

Intravesical gemcitabine (Gem) has shown promising activity against transitional cell carcinomas (TCC) of the bladder, with moderate urinary toxicity and low systemic absorption. The present phase II study evaluated the activity of biweekly intravesical treatment with Gem using a scheme directly derived from in vitro preclinical studies. Patients with Bacille Calmette-Guérin (BCG) -refractory Ta G3, T1 G1-3 TCC underwent transurethral bladder resection and then intravesical instillation with 2000 mg Gem diluted in 50 ml saline solution on days 1 and 3 for 6 consecutive weeks. Thirty-eight (95%) of the 40 patients showed persistent negative post-treatment cystoscopy and cytology 6 months after Gem treatment, while the remaining 2 patients relapsed at 5 and 6 months. At a median follow-up of 28 months, recurrences had occurred in 14 patients. Among these, four had downstaged (T) disease, three had a lower grade (G) lesion and three had a reduction in both T and G. Urinary and systemic toxicity was very low, with no alterations in biochemical profiles. In conclusion, biweekly instillation of Gem proved active in BCG-refractory Ta G3, T1 G1-3 TCC. Our results highlight the importance of preclinical studies using in vitro systems that adequately reproduce the conditions of intravesical clinical treatment to define the best therapeutic schedule.


Assuntos
Carcinoma de Células de Transição/tratamento farmacológico , Desoxicitidina/análogos & derivados , Neoplasias da Bexiga Urinária/tratamento farmacológico , Administração Intravesical , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/farmacologia , Antimetabólitos Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Vacina BCG/uso terapêutico , Carcinoma de Células de Transição/patologia , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Desoxicitidina/administração & dosagem , Desoxicitidina/farmacologia , Desoxicitidina/uso terapêutico , Relação Dose-Resposta a Droga , Resistencia a Medicamentos Antineoplásicos , Feminino , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Transferência de Tecnologia , Neoplasias da Bexiga Urinária/patologia , Gencitabina
14.
Ann Oncol ; 17(8): 1283-9, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16728483

RESUMO

BACKGROUND: The risk of non-Hodgkin's lymphoma (NHL) seems to be enhanced by cigarette smoking and lowered by alcohol drinking. PATIENTS AND METHODS: To assess whether cigarette smoking and alcohol drinking affect NHL survival, a population-based prospective study on 1138 Italian patients, diagnosed in 1991-1993, followed-up until 2002, was carried out. At diagnosis, clinical and socio-demographic data were recorded and lifestyle habits were assessed through a validated questionnaire. Survival analysis was performed with Kaplan-Meier methods. Hazard ratios (HR) were estimated by Cox regression. RESULTS: The mean follow-up was 6.6 years (standard deviation (SD) 4.3). The mean survival time was 7.56 years (SD 0.155). At both univariate and multivariate analysis heavy cigarette smoking and alcohol drinking were associated with poor survival. Compared with those with a lower cumulative exposure to tobacco smoking, those who had smoked>31 pack-years had a worse survival (HR=1.60, 95%CI=1.18-2.18). Drinkers had a higher risk of death compared with non-drinkers (HR=1.41, 95%CI=1.10-1.81). Considering only those who had NHL as cause of death, the HR for the higher category of pack-years smoked, compared with the lowest, was 1.63 (95% CI=1.15-2.33) and for drinkers, compared with non-drinkers, it was 1.33 (95% CI=1.01-1.80). CONCLUSIONS: cigarette smoking and alcohol drinking may influence NHL survival.


Assuntos
Consumo de Bebidas Alcoólicas , Linfoma não Hodgkin/mortalidade , Fumar , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , População , Fatores de Risco
15.
Eur J Cancer Prev ; 14(4): 337-44, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16030423

RESUMO

Most studies of cancer risk related to agricultural exposures have focused on male operators. Cancer mortality in a cohort of 38 962 women engaged in agriculture (Province of Forlì, 1969-1993) was compared with that of the rest of the female residents using the ratio of age-standardized (Europe) mortality rates (ASR) with 95% confidence interval (CI). Moreover, mortality time trends in both subsets of the population were evaluated. The cohort yielded 798 439 person-years with 2397 cancer deaths. Total ASR ratio was 0.86 (95% CI 0.80-0.92). Only gastric cancer was associated with a significant but declining excess mortality (ASR ratio 1.26; 95% CI 1.11-1.43). Total ASR ratio decreased from 1.07 (95% CI 0.95-1.20) in 1969-1976 to 0.74 (95% CI 0.66-0.82) in 1985-1993. This resulted from a downward mortality trend restricted to the cohort. In particular, mortality from cancers of the oesophagus, stomach and colon/rectum decreased more steeply in the cohort. Mortality from liver cancer decreased only in the cohort. Mortality from cancers of the pancreas, lung, breast, bladder and skin melanoma remained stable in the cohort whilst increasing in the rest of the population. In conclusion, risk excesses previously reported were not confirmed. Agricultural workers qualified as a subset of the female population with atypical, favourable epidemiologic characteristics.


Assuntos
Agricultura , Poluentes Ocupacionais do Ar/efeitos adversos , Causas de Morte , Neoplasias/mortalidade , Adulto , Distribuição por Idade , Idoso , Estudos de Coortes , Intervalos de Confiança , Feminino , Humanos , Incidência , Itália/epidemiologia , Pessoa de Meia-Idade , Neoplasias/diagnóstico , Razão de Chances , Sistema de Registros , Medição de Risco
16.
Ann Oncol ; 14(4): 559-63, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12649101

RESUMO

BACKGROUND: The aim of this study was to evaluate the effectiveness of granulocyte-macrophage colony-stimulating factor (GM-CSF) mouthwashes in the prevention of severe mucositis induced by high doses of chemotherapy. PATIENTS AND METHODS: Ninety consecutive patients affected by solid tumors and undergoing high-dose chemotherapy with autologous peripheral blood stem cell transplantation rescue were randomized to receive placebo versus GM-CSF mouthwash 150 micro g/day. Patients were stratified on the basis of the conditioning treatment and the consequent different risk of severe oral mucositis. Treatment was administered from the day after the end of chemotherapy until the resolution of stomatitis and/or neutrophil recovery. RESULTS: The statistical analyses were intention-to-treat and involved all patients who entered the study. The severity of stomatitis was evaluated daily by the physicians according to National Cancer Institute Common Toxicity Criteria. Both study and control groups were compared with respect to the frequency [30% versus 36%, chi(2) exact test, not significant (NS)] and mean duration (4.8 +/- 4.7 versus 4.4 +/- 2.7 days, t-test, NS) of severe stomatitis (grade > or =3). Oral pain was evaluated daily by patients themselves by means of a 10 cm analog visual scale: the mean (+/- standard error of the mean) maximum mucositis scores were 4.8 +/- 3.5 versus 4.2 +/- 3.5 cm (t-test, NS). Furthermore, 15/46 patients in the study group (33%) and 19/44 patients in the control group experienced pain requiring opioids (chi(2) exact test, NS). CONCLUSION: We did not find any evidence to indicate that prophylaxis with GM-CSF mouthwash can help to reduce the severity of mucositis in the setting of the patients we studied.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Mucosa Bucal/patologia , Estomatite/induzido quimicamente , Estomatite/prevenção & controle , Administração Oral , Adolescente , Adulto , Método Duplo-Cego , Feminino , Fator Estimulador de Colônias de Granulócitos e Macrófagos/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Transplante de Células-Tronco de Sangue Periférico , Placebos , Índice de Gravidade de Doença , Resultado do Tratamento
17.
Br J Cancer ; 88(1): 47-9, 2003 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-12556958

RESUMO

In a population-based case-control study among adults in Italy, of 261 lymphoid and 313 myeloid leukaemias and 1718 controls, a later age at adenoidectomy and tonsillectomy (after age 10 years) increased considerably the risk of lymphocytic (but not myeloid) leukaemia (odds ratio 4.2, 95% confidence interval 1.1-16.2). We propose that late infection is a proliferative stimulus for B-cells.


Assuntos
Adenoidectomia/efeitos adversos , Infecções por Vírus Epstein-Barr/complicações , Leucemia/etiologia , Complicações Pós-Operatórias/virologia , Tonsilectomia/efeitos adversos , Adulto , Idoso , Estudos de Casos e Controles , Divisão Celular , Herpesvirus Humano 4 , Humanos , Leucemia/patologia , Leucemia/virologia , Pessoa de Meia-Idade
18.
Br J Cancer ; 87(8): 868-75, 2002 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-12373601

RESUMO

We investigated a number of biological markers, evaluated under strict intralaboratory quality control conditions, in terms of their role in predicting clinical outcome of patients with colon cancer treated with 5-FU-containing regimens. Colon cancer tissue from 263 patients enrolled onto two randomised clinical trials were studied for their cytofluorimetrically determined DNA content and their immunohistochemically evaluated microvessel density, vascular endothelial growth factor expression, thymidylate synthase expression and tumour lymphocyte infiltration. Disease-free survival and overall survival of patients were analysed as a function of the different variables. At a median follow up of 57 months, age, gender and Dukes' stage showed an impact on disease-free survival, whereas no biological marker emerged as an indicator of better or worse disease-free survival. Only histological grade and Dukes' stage were found to influence overall survival. The different biological variables, studied with particular attention for determination reliability, proved to have no impact on the clinical outcome of patients with colon cancer. Therefore, other markers must be identified to complement clinico-pathological variables in the management of this disease.


Assuntos
Adenocarcinoma/diagnóstico , Biomarcadores Tumorais/metabolismo , Neoplasias do Colo/diagnóstico , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/metabolismo , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/metabolismo , Intervalo Livre de Doença , Fatores de Crescimento Endotelial/metabolismo , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Linfócitos do Interstício Tumoral/patologia , Linfocinas/metabolismo , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Taxa de Sobrevida , Timidilato Sintase/metabolismo , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio Vascular
19.
Pathologica ; 94(4): 190-5, 2002 Aug.
Artigo em Italiano | MEDLINE | ID: mdl-12325417

RESUMO

Sentinel lymph node (SLN) analysis allows the detection of occult metastases in patients with melanoma. The use of serial sections and immunohistochemical investigations (ICH) increases the chance of identifying metastases. Nevertheless, detection of mRNA of the tyrosinase gene through reverse transcription-polymerase chain reaction (RT-PCR) is the most sensitive tool for detection of occult melanoma cells in SLN. From September 1999 to August 2001, in the Anatomic Pathology Unit of M. Bufalini Hospital of Cesena, 489 SLNs from 332 patients with primary melanoma in clinical stages I and II (according to AJCC) were examined. There were 66 (13.5%) SLNs and 58 (17.4%) cases with metastasis revealed by histology and ICH. A single case with metastatic SLN was found in patients with melanomas < or = 1 mm in thickness. The percentage of cases with metastases in SLN correlated with thickness of the primary melanoma (p < 0.0001). RT-PCR for tyrosinase was carried out in 448 SLNs from of 308 cases. Overall, the RT-PCR results were positive in 149 (48.4%) patients and in 169 SLNs (37.9%). RT-PCR results showed a strong positive correlation with tumor thickness of primary melanoma (p < 0.0001) and with the clinical stage (p < 0.0001). Of the RT-PCR-positive cases, 18 showed intracapsular aggregates of nevus cells. Besides the percentage of positive cases, once those with nevus aggregates were excluded, overall, the RT-PCR revealed the presence of tyrosinase mRNA in 34.5% of patients with negative histology and ICH. Ongoing monitoring is necessary to define the real prognostic implication of the presumed presence of occult melanoma deposits disclosed by RT-PCR in SLNs.


Assuntos
Biomarcadores Tumorais/genética , Metástase Linfática/patologia , Melanoma/secundário , Monofenol Mono-Oxigenase/genética , Proteínas de Neoplasias/genética , RNA Mensageiro/análise , RNA Neoplásico/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Biópsia de Linfonodo Sentinela , Adulto , Antígenos de Neoplasias/análise , Biomarcadores Tumorais/análise , Feminino , Humanos , Metástase Linfática/diagnóstico , Metástase Linfática/diagnóstico por imagem , Metástase Linfática/genética , Masculino , Melanoma/química , Melanoma/diagnóstico por imagem , Melanoma/genética , Antígenos Específicos de Melanoma , Pessoa de Meia-Idade , Proteínas de Neoplasias/análise , Estadiamento de Neoplasias , RNA Mensageiro/genética , RNA Neoplásico/genética , Cintilografia , Compostos Radiofarmacêuticos , Proteínas S100/análise , Sensibilidade e Especificidade , Agregado de Albumina Marcado com Tecnécio Tc 99m
20.
Breast Cancer Res Treat ; 68(2): 101-10, 2001 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11688513

RESUMO

The predictivity of tumour size, oestrogen (ER) and progesterone (PgR) receptors, 3H-thymidine labelling index (TLI), c-erbB-2 and p27kip1 expression on clinical outcome was analysed on a consecutive series of 118 postmenopausal patients with ER-positive, node-positive tumours. All patients were treated with surgery +/- radiotherapy and adjuvant tamoxifen (30 mg/day) for at least 2 years. TLI, ER, c-erbB-2 and p27kip1 were generally unrelated to each other. PgR was directly related to ER and inversely to c-erbB-2. Tumour size was inversely related to both c-erbB-2 and p27kip1 expression. At a median follow-up of 75 months, 5-year relapse-free survival was significantly lower for patients with very rapidly proliferating (HR = 2.61, 95% CI = 1.34-5.08), PgR negative (HR = 2.76, 95% CI = 1.43-5.33) or relatively low ER content (HR = 2.20, 95% CI = 1.14-4.25) tumours than for patients with tumours expressing the opposite biological profiles. Overall survival was also significantly different as a function of TLI (HR = 3.47, 95% CI = 1.52-7.93) and PgR (HR = 2.27, 95% CI = 1.00-5.15). TLI and PgR maintained an independent relevance in multivariate analysis and together were capable of identifying subgroups of patients at significantly different risk of relapse and death.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/tratamento farmacológico , Proteínas Musculares , Tamoxifeno/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Quimioterapia Adjuvante , Feminino , Humanos , Linfonodos/patologia , Proteínas dos Microfilamentos/metabolismo , Pessoa de Meia-Idade , Prognóstico , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Taxa de Sobrevida , Timidina/metabolismo , Resultado do Tratamento
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