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1.
Expert Rev Endocrinol Metab ; 18(5): 387-398, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37743651

RESUMO

INTRODUCTION: In the treatment scenario of PanNETs-targeted therapies are desired but limited, as rarity and heterogeneity on PanNETs pose limitations to their development. AREAS COVERED: We performed a literature review searching for promising druggable biomarkers and potential treatments to be implemented in the next future. We focused on treatments which have already reached clinical experimentation, although in early phases. Six targets were identified, namely Hsp90, HIFa, HDACs, CDKs, uPAR, and DDR. Even though biological rational is strong, so far reported efficacy outcomes are quite disappointing. The reason of that should be searched in the patients' heterogeneity, lack of biomarker selection, poor knowledge of interfering mechanisms as well as difficulties in patients accrual. Moreover, different ways to assess treatment efficacy should be considered, other than response rate, in light of the more indolent nature of NETs. EXPERT OPINION: Development of targeted treatments in PanNETs is still an uncovered area, far behind other more frequent cancers. Rarity of NETs led to accrual of unselected populations, possibly jeopardizing the drug efficacy. Better patients' selection, both in terms of topography, grading and biomarkers is crucial and will help understanding which role targeted therapies can really play in these tumors.


Assuntos
Tumores Neuroendócrinos , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Tumores Neuroendócrinos/tratamento farmacológico , Tumores Neuroendócrinos/patologia , Resultado do Tratamento , Biomarcadores Tumorais , Seleção de Pacientes
2.
ESMO Open ; 7(5): 100567, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35994791

RESUMO

BACKGROUND: The presence of KRASG12C mutation in metastatic colorectal cancer (mCRC) correlates with poor outcome. Although different selective inhibitors are under clinical development, the optimal treatment remains uncertain. Thus, we conducted a retrospective analysis in a large cohort of patients with KRASG12C mCRC treated in 12 Italian oncology units. PATIENTS AND METHODS: Patients with unresectable mCRC harboring KRASG12C mutation receiving a first-line chemotherapy doublet or triplet between 2011 and 2021 were included in the study. Evaluation of overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) analysis was carried out. RESULTS: A total of 256/6952 (3.7%) patients with mCRC displayed KRASG12C mutation; of these, 111 met the inclusion criteria. The ORR of first-line therapy was 38.7% (43/111). Median PFS (mPFS) was 9 months [95% confidence interval (CI) 7.5-10.5 months]. After progression, only 62% and 36% of the patients are fit to receive second or third lines of treatment, with limited clinical benefit. Median OS (mOS) was 21 months (95% CI 17.4-24.6 months). In patients receiving first-line triplet chemotherapy, ORR was 56.3% (9/16), mPFS was 13 months (95% CI 10.3-15.7 months) and mOS was 32 months (95% CI 7.7-56.3 months). For irinotecan-based doublets, ORR was 34.5 (10/29), mPFS was 9 months (95% CI 6.4-11.6 months) and mOS was 22 months (95% CI 16.0-28.0 months). With oxaliplatin-based doublets ORR was 36.4% (24/62), mPFS was 7 months (95% CI 4.6-9.4 months) and mOS was 18 months (95% CI, 13.6-22.4 months). CONCLUSION: Patients with KRASG12C-mutant mCRC had a disappointing response to standard treatments. Within the limitations of a retrospective study, these results suggest that first-line chemotherapy intensification with FOLFOXIRI is a valid option in fit patients.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Humanos , Oxaliplatina/farmacologia , Oxaliplatina/uso terapêutico , Irinotecano/farmacologia , Irinotecano/uso terapêutico , Estudos Retrospectivos , Fluoruracila/efeitos adversos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resultado do Tratamento , Neoplasias do Colo/tratamento farmacológico
3.
Ann Oncol ; 32(1): 66-76, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33098997

RESUMO

BACKGROUND: Oxaliplatin-based adjuvant chemotherapy is the standard treatment of high-risk colon cancer (CC). A shorter duration (3 months) can achieve a similar outcome [in terms of relapse-free survival (RFS)] to a longer duration. This study reports the overall survival (OS) analysis of the three or six colon adjuvant (TOSCA) phase III study. It assessed different adjuvant chemotherapy durations in patients with resected high-risk stage II and stage III CC. MATERIAL AND METHODS: TOSCA was an open-label, phase III, multicentre, non-inferiority trial conducted in 130 Italian centres. Patients were randomly assigned, in a 1 : 1 ratio, to receive 3 months of standard doses of FOLFOX/CAPOX, or 6 months of FOLFOX/CAPOX. Patients with histologically confirmed high-risk stage II and III CC were included, with RFS being the primary end point. OS was a secondary end point. RESULTS: From June 2007 to March 2013, 3759 patients were accrued. At a median follow-up of 7 years, the hazard ratio (HR) for RFS of the 3-month versus 6-month arms was 1.13; 95% confidence interval (CI) 0.99-1.29, P for non-inferiority = 0.380, P for superiority = 0.068, crossing the non-inferiority limit of 1.20. This result did not allow us to reject the null hypothesis of the inferiority of the 3-month arm. The HR for OS of the 3-month versus 6-month arms was 1.09 (95% CI 0.93-1.26, P for superiority = 0.288). At the last follow-up analysis, the absolute OS difference between arms was <1%. CONCLUSIONS: The present analysis of the TOSCA trial does not indicate any significant difference in OS between the treatment groups. The extra benefit provided by the longer treatment should be balanced against the extra toxicity of more prolonged therapy. The trial is registered with ClinicalTrials.gov, registration number: NCT0064660.


Assuntos
Fluoruracila , Recidiva Local de Neoplasia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina/uso terapêutico , Quimioterapia Adjuvante , Intervalo Livre de Doença , Fluoruracila/efeitos adversos , Humanos , Itália , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias
4.
Med Oncol ; 35(5): 59, 2018 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-29594584

RESUMO

Intensity-modulated radiotherapy (IMRT) is considered the preferred option in squamous cell canal cancer (SCAC), delivering high doses to tumor volumes while minimizing dose to surrounding normal tissues. IMRT has steep dose gradients, but the technique is more demanding as deep understanding of target structures is required. To evaluate genital marginal failure in a cohort of patients with non-metastatic SCAC treated either with IMRT or 3DCRT and concurrent chemotherapy, 117 patients with SCAC were evaluated: 64 and 53 patients were treated with IMRT and 3DCRT techniques, respectively. All patients underwent clinical and radiological examination during their follow-up. Tumor response was evaluated with response evaluation criteria in solid tumors v1.1 guideline on regular basis. All patients' data were analyzed, and patients with marginal failure were identified. Concomitant chemotherapy was administered in 97 and 77.4% of patients in the IMRT and 3DCRT groups, respectively. In the IMRT group, the median follow-up was 25 months (range 6-78). Progressive disease was registered in 15.6% of patients; infield recurrence, distant recurrence and both infield recurrence and distant recurrence were identified in 5, 4 and 1 patient, respectively. Two out of 64 patients (3.1%) had marginal failures, localized at vagina/recto-vaginal septum and left perineal region. In the 3DCRT group, the median follow-up was 71.3 months (range 6-194 months). Two out of 53 patients (3.8%) had marginal failures, localized at recto-vaginal septum and perigenital structures. The rate of marginal failures was comparable in IMRT and 3DCRT groups (χ2 test p = 0.85). In this series, the use of IMRT for the treatment of SCAC did not increase the rate of marginal failures offering improved dose conformity to the target. Dose constraints should be applied with caution-particularly in females with involvement of the vagina or the vaginal septum.


Assuntos
Neoplasias do Ânus/patologia , Neoplasias do Ânus/radioterapia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/radioterapia , Genitália/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Ânus/tratamento farmacológico , Carcinoma de Células Escamosas/tratamento farmacológico , Quimiorradioterapia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Planejamento da Radioterapia Assistida por Computador , Radioterapia Conformacional , Radioterapia de Intensidade Modulada , Estudos Retrospectivos , Falha de Tratamento
7.
Pharmazie ; 72(4): 200-204, 2017 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-29441987

RESUMO

Lipid microparticles (LMs) loaded with the antioxidant polyphenol, trans-resveratrol were developed in order to enhance its photostability in topical formulations. The LMs were prepared by the melt emulsification technique, using tristearin as the lipidic material and hydrogenated phosphatidylcholine as the surfactant. The obtained microparticles were characterized by optical microscopy and release studies. The trans-resveratrol loading was 10.8% (w/w). Free or microencapsulated trans-resveratrol was introduced in model topical formulations (cream and hydrogel) and irradiated with a solar simulator. The light-induced degradation of trans-resveratrol was significantly reduced by incorporation into the LMs both in the cream (the trans-resveratrol loss decreased from 34.3% to 19.9%) and in the hydrogel (the trans-resveratrol decomposition decreased from 15.4% to 9.4%) vehicles. Moreover, the in vitro (i.e., antioxidant action) and in vivo (i.e., anti-inflammatory action) biological activities of trans-resveratrol in the cream preparation were not altered by the encapsulation process.


Assuntos
Anti-Inflamatórios/administração & dosagem , Antioxidantes/administração & dosagem , Lipídeos/química , Estilbenos/administração & dosagem , Adulto , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Química Farmacêutica/métodos , Estabilidade de Medicamentos , Emulsões , Feminino , Humanos , Hidrogéis , Masculino , Microscopia/métodos , Microesferas , Fosfatidilcolinas/química , Fotólise , Resveratrol , Creme para a Pele , Estilbenos/química , Estilbenos/farmacologia , Tensoativos/química , Triglicerídeos/química , Adulto Jovem
8.
Crit Rev Oncol Hematol ; 108: 154-163, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27931834

RESUMO

A major challenge for the management of advanced-colorectal-cancer is the multidisciplinary approach required for the treatment of liver metastases. Reducing the burden of liver metastases with liver-directed therapy has an important impact on both survival and health-related quality of life. This paper debates the rationale and current liver-directed approaches for colorectal liver metastases based on the evidence of literature and new clinical trials. Surgery is the gold standard, when feasible, and it's the main treatment goal for patients with potentially-resectable disease as a means of prolonging progression-free survival. Better tumor response rates with modern systemic therapy mean that more unresectable patients are now down-staged for radical resection following conversion therapy but for other patients, additional procedures are needed. In multiple unilobar disease, when the projected remnant liver is <30% of the total liver, portal embolization or selective-internal-radiation-therapy (SIRT) can induce hypertrophy of the healthy liver, leading to resectability. In multiple bilobar disease, in situ destruction of non-resectable lesions by minimally invasive techniques may be associated with liver resection to achieve potential curative intent. Other palliative liver-directed approaches, such as SIRT or intra-hepatic chemotherapy (HAI), which are associated with higher response rates, may also have role in down-staging patients for resection. Until recently, such technologies have not been validated in prospective controlled trials. However in the light of new Phase 3 data for SIRT as well as for HAI combined with modern therapies or radiofrequency ablation in the first- and second-line setting, the clinical value of these treatments needs to be re-appraised.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Neoplasias Hepáticas/terapia , Quimioembolização Terapêutica , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Hepatectomia , Humanos , Neoplasias Hepáticas/secundário , Qualidade de Vida
9.
Ann Oncol ; 27(11): 2074-2081, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27573560

RESUMO

BACKGROUND: Six months of oxaliplatin-based adjuvant chemotherapy is standard of care for radically resected stage III colon cancer and an accepted option for high-risk stage II. A shorter duration of therapy, if equally efficacious, would be advantageous for patients and Health-Care Systems. PATIENTS AND METHODS: TOSCA ['Randomized trial investigating the role of FOLFOX-4 or XELOX (3 versus 6 months) regimen duration and bevacizumab as adjuvant therapy for patients with stage II/III colon cancer] is an open-label, phase III, multicenter, noninferiority trial randomizing patients with high-risk stage II or stage III radically resected colon cancer to receive 3 months (arm 3 m) versus 6 months (arm 6 m) of FOLFOX4/XELOX. Primary end-point was relapse-free survival. We present here safety and compliance data. RESULTS: From June 2007 to March 2013, 3759 patients were accrued from 130 Italian sites, 64% receiving FOLFOX4 and 36% XELOX in either arm. Treatment completion rate without any modification was 35% versus 12% and with delays or dose reduction 52% versus 44% in arm 3 and 6 m. Treatment was permanently discontinued in 8% (arm 3 m) and 33% (arm 6 m). In arm 6 m, 50% of patients discontinuing treatment did so after completing 80% of planned program. Grade 3+ toxicities were higher in arm 6 m than that in 3 m. Grade 2+ neuropathy was 31.2% versus 8.8% (P < 0.0001) while grade 3+ was 8.4 versus 1.3 (P < 0.0001), in arm 3 and 6 m. Seven deaths within 30 days from last treatment administration in arm 6 m and three deaths in arm 3 m were observed (0.3% versus 0.1%, P = 0.34). CONCLUSIONS: TOSCA is the first trial comparing 3 versus 6 months of adjuvant chemotherapy completing accrual within the international initiative of treatment duration evaluation (International Duration Evaluation of Adjuvant, IDEA). High compliance to treatment in control arm will allow a correct assessment of potential differences between the two treatment durations. CLINICALTRIALSGOV REGISTRATION NUMBER: NCT00646607.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias do Colo/tratamento farmacológico , Desoxicitidina/análogos & derivados , Fluoruracila/análogos & derivados , Recidiva Local de Neoplasia/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/administração & dosagem , Capecitabina , Quimioterapia Adjuvante/efeitos adversos , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Terapia Combinada , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Oxaliplatina , Oxaloacetatos , Cooperação do Paciente
10.
Ann Oncol ; 27(4): 668-73, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26712905

RESUMO

BACKGROUND: Fluorouracil-based adjuvant chemotherapy in gastric cancer has been reported to be effective by several meta-analyses. Perioperative chemotherapy in locally advanced resectable gastric cancer (RGC) has been reported improving survival by two large randomized trials and recent meta-analyses but the role of neoadjuvant chemotherapy and optimal regimen remains to be determined. We compared a neoadjuvant with adjuvant docetaxel-based regimen in a prospective randomized phase III trial, of which we present the 10-year follow-up data. PATIENTS AND METHODS: Patients with cT3-4 anyN M0 or anyT cN1-3 M0 gastric carcinoma, staged with endoscopic ultrasound, computed tomography, bone scan, and laparoscopy, were assigned to receive four 21-day/cycles of docetaxel 75 mg/m(2) day 1, cisplatin 75 mg/m(2) day 1, and fluorouracil 300 mg/m(2)/day over days 1-14, either before (arm A) or after (arm B) gastrectomy. Event-free survival was the primary end point, whereas secondary end points included overall survival, toxicity, down-staging, pathological response, quality of life, and feasibility of adjuvant chemotherapy. RESULTS: This trial was activated in November 1999 and closed in November 2005 due to insufficient accrual. Of the 70 enrolled patients, 69 were randomized, 34 to arm A and 35 to arm B. No difference in EFS (2.5 years in both arms) or OS (4.3 versus 3.7 years, in arms A and B, respectively) was found. A higher dose intensity of chemotherapy was observed in arm A and more frequent chemotherapy-related serious adverse events occurred in arm B. Surgery was safe after preoperative chemotherapy. A 12% pathological complete response was observed in arm A. CONCLUSION: Docetaxel/cisplatin/fluorouracil chemotherapy is promising in preoperative setting of locally advanced RGC. The early stopping could mask the real effectiveness of neoadjuvant treatment. However, the complete pathological tumour responses, feasibility, and safe surgery warrant further investigation of a taxane-based regimen in the preoperative setting.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Terapia Neoadjuvante , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adolescente , Adulto , Idoso , Cisplatino/administração & dosagem , Intervalo Livre de Doença , Docetaxel , Fluoruracila/administração & dosagem , Gastrectomia , Humanos , Pessoa de Meia-Idade , Período Perioperatório , Período Pós-Operatório , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Taxoides/administração & dosagem , Resultado do Tratamento
11.
Minerva Chir ; 66(6): 527-35, 2011 Dec.
Artigo em Italiano | MEDLINE | ID: mdl-22233659

RESUMO

AIM: The aim of this study was to evaluate technical feasibility, oncological safety and short-term clinical results of robotic rectal resection for cancer. METHODS: From January 2008 to July 2010, 46 patients (27 males and 19 females, median age 69 years, median BMI 24.6 kg/m2) with histologically-proven adenocarcinoma of medium and distal rectum were enrolled in a prospective database. Preoperative assessment was performed with colonoscopy with biopsies, thoraco-abdominal CT scan, pelvic MRI and endorectal-ultrasound (ERUS). In the case of locally advanced non metastatic disease (T3/4 or N1/2), patients received preoperative radiotherapy (45 Grays in 5 weeks) and chemotherapy (oral Capecitabine). The robotic system was a four-arms Da Vinci® (Intuitive Surgical, Sunnyvale, CA, USA); arms position is not modified during the entire surgical procedure. RESULTS: Twenty-five patients received a preoperative radio-chemotherapy. Surgical procedure was an abdomino-perineal amputation in nine patients and an anterior resection in the remaining 37, with temporary ileostomy in 16 cases and a laparoscopic mobilization of splenic flexure in 25. Median operative time was 251 minutes, median time of first bowel movements 1.7 days and median hospital stay 6.7 days. Major complications requiring reoperation verified in 2 patients, while overall complication rate is 15.2%. Median number of harvested lymph nodes per patient was 18; median distance of the tumour from distal resection margin was 2 cm; distance of the tumour from circumferential margin was superior to 1 mm in all of the patients. At a median follow up of 11 months, all patients are alive and disease-free. CONCLUSION: Robotic rectal resection is a feasible technique which can provide good oncological and short-term clinical results.


Assuntos
Adenocarcinoma/cirurgia , Laparoscopia , Neoplasias Retais/cirurgia , Robótica , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Adenocarcinoma/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Cuidados Pré-Operatórios , Estudos Prospectivos , Radioterapia Adjuvante , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/patologia , Neoplasias Retais/radioterapia , Resultado do Tratamento
12.
Surg Endosc ; 24(11): 2888-94, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20526623

RESUMO

BACKGROUND: We assessed feasibility, short-term oncologic safety, and short-term outcomes in robotic total mesorectal excision (R-TME) for rectal cancer compared with laparoscopic TME. METHODS: From March 2008 to June 2009, 50 patients with proven middle/lower rectal adenocarcinoma underwent minimally invasive TME; 25 received R-TME. The groups were balanced (R-TME versus L-TME) in terms of age (median 69 versus 62 years; p = 0.8), disease stage, and body mass index (median 23 versus 26.5 kg/m(2); p = 0.06). There were 37 (74%) anterior resections and 13 (26%) abdominoperineal resections. Twenty-three (46%) patients received preoperative radiochemotherapy. The robot was a four-arm Da Vinci S (Intuitive Surgical, Sunnyvale, CA, USA). RESULTS: Median operating time (R-TME versus L-TME) was 240 versus 237 min (p = 0.2); first bowel movement was 2 versus 3 days (p = 0.5); median hospital stay was 6.5 versus 6 days (p = 0.4). Major complications with reoperation were two in R-TME (one anastomotic leakage, one small bowel perforation) and three in L-TME (one colonic ischemia, two anastomotic leakage). Postoperative complications were 16% versus 24% (p = 0.5). A median of 18 versus 17 (p = 0.7) lymph nodes were retrieved; distal resection margins were disease free in both groups; circumferential margin was involved (<1.0 mm) in one (4%) of L-TME. There were 0 versus 1 (5%) conversions to laparotomy. CONCLUSIONS: R-TME in rectal cancer is feasible, with short-term oncologic and other outcomes similar to those of L-TME. The greater maneuverability and visibility afforded by the robotic approach are attractive. Future studies should more systematically address advantages and costs of R-TME.


Assuntos
Adenocarcinoma/cirurgia , Laparoscopia , Neoplasias Retais/cirurgia , Reto/cirurgia , Robótica , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Complicações Intraoperatórias , Laparoscopia/efeitos adversos , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Neoplasias Retais/patologia
14.
Crit Rev Oncol Hematol ; 72(1): 65-75, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19147371

RESUMO

Colorectal cancer (CRC) caused nearly 204,000 deaths in Europe in 2004. Despite recent advances in the treatment of advanced disease, which include the incorporation of two new cytotoxic agents irinotecan and oxaliplatin into first-line regimens, the concept of planned sequential therapy involving three active agents during the course of a patient's treatment and the integrated use of targeted monoclonal antibodies, the 5-year survival rates for patients with advanced CRC remain unacceptably low. For patients with colorectal liver metastases, liver resection offers the only potential for cure. This review, based on the outcomes of a meeting of European experts (surgeons and medical oncologists), considers the current treatment strategies available to patients with CRC liver metastases, the criteria for the selection of those patients most likely to benefit and suggests where future progress may occur.


Assuntos
Neoplasias Colorretais/patologia , Hepatectomia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Antineoplásicos/uso terapêutico , Ensaios Clínicos como Assunto , Neoplasias Colorretais/mortalidade , Terapia Combinada , Humanos , Terapia Neoadjuvante , Guias de Prática Clínica como Assunto
15.
Ann Oncol ; 20(5): 935-40, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19179550

RESUMO

BACKGROUND: Central venous access is extensively used in oncology, though practical information from randomized trials on the most convenient insertion modality and site is unavailable. METHODS: Four hundred and three patients eligible for receiving i.v. chemotherapy for solid tumors were randomly assigned to implantation of a single type of port (Bard Port, Bard Inc., Salt Lake City, UT), through a percutaneous landmark access to the internal jugular, a ultrasound (US)-guided access to the subclavian or a surgical cut-down access through the cephalic vein at the deltoid-pectoralis groove. Early and late complications were prospectively recorded until removal of the device, patient's death or ending of the study. RESULTS: Four hundred and one patients (99.9%) were assessable: 132 with the internal jugular, 136 with the subclavian and 133 with the cephalic vein access. The median follow-up was 356.5 days (range 0-1087). No differences were found for early complication rate in the three groups {internal jugular: 0% [95% confidence interval (CI) 0.0% to 2.7%], subclavian: 0% (95% CI 0.0% to 2.7%), cephalic: 1.5% (95% CI 0.1% to 5.3%)}. US-guided subclavian insertion site had significantly lower failures (e.g. failed attempts to place the catheter in agreement with the original arm of randomization, P = 0.001). Infections occurred in one, three and one patients (internal jugular, subclavian and cephalic access, respectively, P = 0.464), whereas venous thrombosis was observed in 15, 8 and 11 patients (P = 0.272). CONCLUSIONS: Central venous insertion modality and sites had no impact on either early or late complication rates, but US-guided subclavian insertion showed the lowest proportion of failures.


Assuntos
Antineoplásicos/administração & dosagem , Veias Braquiocefálicas , Cateterismo Venoso Central/métodos , Cateteres de Demora/efeitos adversos , Veias Jugulares , Neoplasias/tratamento farmacológico , Veia Subclávia , Idoso , Infecções Relacionadas a Cateter/etiologia , Infecções Relacionadas a Cateter/prevenção & controle , Cateterismo Venoso Central/efeitos adversos , Cateterismo Venoso Central/instrumentação , Falha de Equipamento , Feminino , Hemorragia/etiologia , Hemorragia/prevenção & controle , Humanos , Masculino , Pessoa de Meia-Idade , Pneumotórax/etiologia , Pneumotórax/prevenção & controle , Estudos Prospectivos , Veia Subclávia/diagnóstico por imagem , Fatores de Tempo , Falha de Tratamento , Ultrassonografia de Intervenção , Trombose Venosa/etiologia , Trombose Venosa/prevenção & controle
16.
Cancer Chemother Pharmacol ; 63(1): 139-48, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18327586

RESUMO

PURPOSE: Epidermal growth factor receptor-overexpression reported in colorectal cancer, justifies therapeutic use of EGFR-inhibitors. We have recently conducted a phase II study in 57 patients with EGFR-positive advanced colorectal cancer (ACC) who received gefitinib-FOLFOX6 followed by gefitinib-single agent as maintenance. Main biological objective was to assess sEGFR as surrogate marker of tyrosine kinase inhibition and as predictor of response. METHODS: sEGFR, evaluated by quantitative ELISA, was investigated as predictive factor both taking into account the basal value only, and its whole pattern over time. sEGFR was collected at baseline and at every 2-months assessment in 42 cases. Thirty-three patients reported CR/PR as best objective response (BOR), while nine showed SD/PD. RESULTS: Retrospectively, on average, the sEGFR values reported by both responders (CR/PR) and not responders (SD/PD) were already different at baseline (49.4 +/- 6.2 and 42.4 +/- 8.4 ng/ml respectively). This difference was statistically significant (p = 0.042). Although sEGFR trend over time confirmed the basal difference (p = 0.032), this result should be taken with caution, due to the small number of patients reporting EGFR values besides the basal one. CONCLUSIONS: Higher sEGFR at baseline was associated to BOR and may be considered a significant predictor of outcome in patients with ACC.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/sangue , Neoplasias Colorretais/tratamento farmacológico , Receptores ErbB/sangue , Proteínas de Neoplasias/sangue , Quinazolinas/uso terapêutico , Adenocarcinoma/sangue , Adenocarcinoma/patologia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/sangue , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Receptores ErbB/genética , Feminino , Fluoruracila/administração & dosagem , Gefitinibe , Humanos , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Compostos Organoplatínicos/administração & dosagem , Prognóstico , Quinazolinas/administração & dosagem , Resultado do Tratamento
17.
Artigo em Inglês | MEDLINE | ID: mdl-22275961

RESUMO

BACKGROUND: An institutional task force on upper gastrointestinal tumours is active at the European Institute of Oncology (EIO). Members decided to collate the institutional guidelines on management of liver tumours (primary and metastatic) into a document. This article is aimed at presenting the current treatment guidelines as well as ongoing research protocols and trials in this field at the EIO. METHODS: A steering committee convened to assign tasks to individual members. Contributions from experts in each treatment area were collated in a single document, in order to produce a draft for subsequent review from the aforementioned committee. Six drafts have been discussed and the final version approved. RESULTS: Surgical, medical oncology, interventional radiology, nuclear medicine and radiation therapy approaches, their roles in management of liver tumours and ongoing research trials are presented and discussed in this article. CONCLUSIONS: At the EIO a multi-disciplinary integrated approach to liver tumours is standard and several ongoing research projects are currently active in this field.

18.
J Eur Acad Dermatol Venereol ; 21(9): 1249-52, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17894714

RESUMO

BACKGROUND: Although a predisposing role of pregnancy to Malassezia infections is referred, data on the prevalence of pityriasis versicolor (PV) in pregnant women are not available in literature. OBJECTIVE: To investigate the frequency of PV during pregnancy, 60 pregnant women were clinically and microscopically investigated during and after pregnancy. RESULTS: Fifty-two women completed all visits; three women were affected by PV at first or third trimester of pregnancy, and none at 6 months after delivery. Colonization due to Malassezia yeasts was very significantly (P < 0.01) or significantly increased (P < 0.05) at the third trimester and 6 months after delivery, respectively. No variation was observed between the end of pregnancy and the postpartum (P > 0.05). CONCLUSION: Frequency of PV during pregnancy (5.7%) does not seem different from that reported in general population living in temperate climates (2-5%). However, higher degree of colonization by Malassezia resulted at the end of pregnancy and postpartum.


Assuntos
Malassezia , Tinha Versicolor/epidemiologia , Adulto , Suscetibilidade a Doenças , Feminino , Humanos , Itália/epidemiologia , Modelos Logísticos , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Prevalência
19.
Radiol Med ; 112(5): 681-90, 2007 Aug.
Artigo em Inglês, Italiano | MEDLINE | ID: mdl-17657420

RESUMO

PURPOSE: The aim of this study was to compare the diagnostic value of multidetector computed tomography (MDCT) and F18-fluorodeoxyglucose positron emission tomography-computed tomography (FDG-PET/CT) for the detection of local and distant recurrence in patients operated on for rectal cancer. MATERIALS AND METHODS: Sixty-seven patients who underwent radical surgery for rectal cancer and were followed up with FDG-PET/CT and MDCT were included in this retrospective study. The FDG-PET/CT and MDCT findings were independently compared with histological sampling or 2 years' follow-up. RESULTS: Local recurrence occurred in 15/67 patients. MDCT diagnosed local recurrence in 15/15 cases and FDG-PET/CT in 14/15. Sensitivity and specificity were 100% and 98% for MDCT and 93% and 98% for FDG-PET/CT, respectively. Hepatic lesions were found in 17/67 patients. All hepatic metastases were detected by both techniques. Pulmonary metastases occurred in 8/67 patients: they were correctly identified in all cases by MDCT and in 6/8 by FDG-PET/CT. CONCLUSIONS: MDCT and FDG-PET/CT showed high sensitivity and specificity for the detection of local recurrence of rectal cancer. Both techniques were equally accurate for the detection of hepatic metastases. MDCT showed slightly higher sensitivity and positive predictive value in detecting pulmonary metastases compared with FDG-PET/CT.


Assuntos
Fluordesoxiglucose F18 , Compostos Radiofarmacêuticos , Neoplasias Retais/diagnóstico por imagem , Tomografia Computadorizada de Emissão/métodos , Tomografia Computadorizada por Raios X/métodos , Feminino , Humanos , Masculino , Metástase Neoplásica/diagnóstico por imagem , Recidiva Local de Neoplasia/diagnóstico por imagem , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , Estudos Retrospectivos , Sensibilidade e Especificidade
20.
Br J Cancer ; 96(7): 1118-26, 2007 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-17375048

RESUMO

Fascin, an actin-bundling protein involved in cell motility, has been shown to be upregulated in several types of carcinomas. In this study, we investigated the expression of fascin in 228 advanced colonic adenocarcinoma patients with a long follow-up. Fascin expression was compared with several clinicopathologic parameters and survival. Overall, fascin immunoreactivity was detected in 162 (71%) tumours with a prevalence for right-sided tumours (P<0.001). Fascin correlated significantly with sex, tumour grade and stage, mucinous differentiation, number of metastatic lymph nodes, extranodal tumour extension, and the occurrence of distant metastases. Patients with fascin-expressing tumours experienced a shorter disease-free and overall survival in comparison with those with negative tumours, and fascin immunoreactivity emerged as an independent prognostic factor in the multivariate analysis. Moreover, patients with the same tumour stages could be stratified in different risk categories for relapse and progression according to fascin expression. Our findings suggest that fascin is a useful prognostic marker for colonic adenocarcinomas.


Assuntos
Adenocarcinoma/metabolismo , Proteínas de Transporte/metabolismo , Neoplasias do Colo/metabolismo , Proteínas dos Microfilamentos/metabolismo , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/metabolismo , Neoplasias do Colo/patologia , Feminino , Humanos , Técnicas Imunoenzimáticas , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Taxa de Sobrevida
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