Asunto(s)
COVID-19 , Neoplasias , Anticuerpos Antivirales , Vacuna BNT162 , Humanos , Neoplasias/tratamiento farmacológicoAsunto(s)
COVID-19 , Neoplasias , Vacunas , Vacuna BNT162 , COVID-19/prevención & control , Humanos , Neoplasias/tratamiento farmacológico , SARS-CoV-2RESUMEN
BACKGROUND: In platinum-sensitive relapsed ovarian cancer, paclitaxel plus carboplatin is a standard second-line treatment. Zibotentan (ZD4054) is an oral, specific ETA-receptor antagonist with demonstrated antitumour activity in xenograft models of human ovarian cancer. METHODS: In this Phase II, randomized, placebo-controlled study, patients with relapsed ovarian cancer sensitive to platinum-based chemotherapy received zibotentan 10mg or placebo once-daily, plus paclitaxel 175 mg/m(2) iv followed by carboplatin iv (AUC 5) on day 1 of every 3-week cycle for a maximum of eight cycles. The primary endpoint was progression-free survival (PFS), evaluated by Response Evaluation Criteria In Solid Tumours (RECIST). Secondary and exploratory endpoints included objective tumour response rate, tumour size, CA-125/RECIST progression, and safety and tolerability. RESULTS: A total of 120 patients were randomized (zibotentan: n=59; placebo: n=61). Addition of zibotentan 10mg/day to carboplatin and paclitaxel did not improve PFS compared with placebo (median PFS, 7.6 versus 10.0 months, respectively; HR=1.46, [80% CI: 1.10-1.94]; P=0.0870). No improvements in any of the secondary or exploratory efficacy endpoints were observed for patients receiving zibotentan compared with placebo. Median duration of total treatment exposure was 6.7 months. Total chemotherapy dose received was lower for zibotentan-treated versus placebo-treated patients (carboplatin: -16%; paclitaxel: -14%). The most common adverse events in the zibotentan arm were anaemia, nausea, alopecia, headache and neutropenia (43-48% of patients). CONCLUSIONS: Zibotentan 10mg/day plus carboplatin and paclitaxel did not result in an improvement in PFS compared with chemotherapy alone in patients with advanced ovarian cancer sensitive to platinum-based chemotherapy. No unexpected safety concerns were identified.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Glandulares y Epiteliales/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carboplatino/administración & dosificación , Carboplatino/efectos adversos , Carcinoma Epitelial de Ovario , Supervivencia sin Enfermedad , Método Doble Ciego , Esquema de Medicación , Femenino , Humanos , Persona de Mediana Edad , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Placebos , Pirrolidinas/administración & dosificación , Pirrolidinas/efectos adversos , Adulto JovenAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Carcinoma Ductal Pancreático/tratamiento farmacológico , Carcinoma Ductal Pancreático/enzimología , Quinasas Quinasa Quinasa PAM/antagonistas & inhibidores , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/enzimología , Inhibidores de las Quinasa Fosfoinosítidos-3 , Inhibidores de Proteínas Quinasas/farmacología , Carcinoma Ductal Pancreático/patología , Procesos de Crecimiento Celular/efectos de los fármacos , Sinergismo Farmacológico , Compuestos Heterocíclicos con 3 Anillos/administración & dosificación , Compuestos Heterocíclicos con 3 Anillos/farmacología , Humanos , Quinasas Quinasa Quinasa PAM/metabolismo , Morfolinas/farmacología , Neoplasias Pancreáticas/patología , Fosfatidilinositol 3-Quinasas/metabolismo , Inhibidores de Proteínas Quinasas/administración & dosificación , Piridonas/administración & dosificación , Piridonas/farmacología , Pirimidinonas/administración & dosificación , Pirimidinonas/farmacología , Triazinas/farmacologíaRESUMEN
BACKGROUND: The purpose of the study was to evaluate the benefit of adjuvant chemotherapy (AC) versus surgery alone in patients with muscle-invasive bladder cancer (MIBC). PATIENTS AND METHODS: One hundred and ninety-four patients with pT2G3, pT3-4, N0-2 transitional cell bladder carcinoma were randomly allocated to control (92 patients) or to four courses of AC (102 patients). These latter patients were further randomly assigned to receive gemcitabine 1000 mg/m(2) days 1, 8 and 15 and cisplatin 70 mg/m(2) day 2 or gemcitabine as above plus cisplatin 70 mg/m(2) day 15, every 28 days. RESULTS: At a median follow-up of 35 months, the 5-year overall survival (OS) was 48.5%, with no difference between the two arms [P = 0.24, hazard ratio (HR) 1.29, 95% confidence interval (CI) 0.84-1.99]. Mortality hazard was significantly correlated with Nodes (N) and Tumor (T) stage. The control and AC arms had comparable disease-free survival (42.3% and 37.2%, respectively; P = 0.70, HR 1.08, 95% CI 0.73-1.59). Only 62% of patients received the planned cycles. A significant higher incidence of thrombocytopenia was observed in patients receiving cisplatin on day 2 (P = 0.006). A similar global quality of life was observed in the two arms. CONCLUSION: The study was underpowered to demonstrate that AC with cisplatin and gemcitabine improves OS and disease-free survival in patients with MIBC.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Carcinoma de Células Transicionales/tratamiento farmacológico , Desoxicitidina/análogos & derivados , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma de Células Transicionales/mortalidad , Carcinoma de Células Transicionales/cirugía , Quimioterapia Adyuvante , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Cistectomía , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Supervivencia sin Enfermedad , Femenino , Humanos , Italia , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Recurrencia , Neoplasias de la Vejiga Urinaria/mortalidad , Neoplasias de la Vejiga Urinaria/cirugía , GemcitabinaRESUMEN
BACKGROUND: Preclinical data suggest that treatment with lapatinib reinduces sensitivity to trastuzumab in human epidermal growth factor receptor 2(HER2)-positive breast cancer cells. PATIENTS AND METHODS: Between January 2007 and November 2010, 179 HER2-positive metastatic breast cancer patients were treated with lapatinib and capecitabine at nine Italian institutions. We evaluated the clinical outcome of 69 patients (38.5%) retreated with trastuzumab after lapatinib progression. RESULTS: Visceral metastases were identified in 51 (74%) and brain metastases in 16 patients (23%). All patients were pretreated with both trastuzumab- and lapatinib-based therapy. We observed with retreatment with trastuzumab-based therapy: 1 complete remission (2%), 18 partial remission (29%) and 10 stable disease ≥6 months (14%) and 47% of clinical benefit (CB). Median duration of response was 8.1 months [95% confidence interval (CI) 5.5-10.7]. No unexpected toxic effects occurred. At a median follow-up of 13 months, median progression-free survival was 4.9 months (95% CI 4.2-5.6) and overall survival (OS) 19.4 months (95% CI 14.0-25.0). Median OS was longer for patients experiencing CB (not reached versus 13.4 months for patients without CB, P = 0.002). Brain involvement was associated with lower median OS (17.3 versus 23.3 months for patients without brain disease; P = 0.021). CONCLUSION: Retreatment with trastuzumab-based therapy showed CB in 47% of patients progressing during lapatinib-based therapy, leading to a prolonged OS.
Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Quinazolinas/farmacología , Receptor ErbB-2/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Resistencia a Antineoplásicos , Femenino , Humanos , Estimación de Kaplan-Meier , Lapatinib , Persona de Mediana Edad , Análisis Multivariante , Metástasis de la Neoplasia , Modelos de Riesgos Proporcionales , Quinazolinas/uso terapéutico , Estudios Retrospectivos , Trastuzumab , Insuficiencia del TratamientoRESUMEN
BACKGROUND: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) are effective as first-line treatment of advanced non-small-cell lung cancer patients with EGFR mutations (EGFR-M+). PATIENTS AND METHODS: We conducted a literature-based meta-analysis to quantify the magnitude of benefit with upfront EGFR TKI in EGFR-M+ patients. Meta-regression and sensitivity analyses were also carried out to identify additional predictors of outcome and to assess the influence of trial design. RESULTS: Five trials (805 patients) were identified (three trials prospectively enrolling EGFR-M+ patients and two retrospective analyses of EGFR-M+ patients). TKI significantly increased progression-free survival (PFS) [hazard ratio (HR) 0.45, 95% confidence interval (CI) 0.36-0.58, P < 0.0001] and overall response rate (ORR) (HR 2.08, 95% CI 1.75-2.46, P < 0.0001)] over chemotherapy, while significantly decreasing neutropenia. No significant difference was observed in overall survival. The rate of exon-19 mutations, female gender, and nonsmoking status were identified as additional predictors of outcome at meta-regression analysis. A significant interaction with trial design was found for both PFS (P = 0.028) and ORR (P = 0.008), suggesting a larger advantage for patients treated within prospective trials. CONCLUSIONS: In EGFR-M+ patients, first-line TKI increase both PFS and ORR by ~25%, while significantly decreasing toxicity. The role of additional predictive factors and the influence of trial design on the magnitude of the observed benefit warrant further investigation.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/enzimología , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/enzimología , Mutación , Inhibidores de Proteínas Quinasas/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/genética , Femenino , Humanos , Neoplasias Pulmonares/genética , Masculino , Inhibidores de Proteínas Quinasas/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores SexualesRESUMEN
BACKGROUND: In the present study, we investigated the clinical outcome of patients with brain metastases (BMs) from human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC) treated with lapatinib and capecitabine (LC). METHODS: Of 81 HER2+ metastatic BC patients treated with LC at two Italian institutions, 30 patients with BMs eligible for the analysis were identified. All patients were pretreated with trastuzumab for metastatic disease. No patients had received prior lapatinib and/or capecitabine. RESULTS: Median age was 45 years (range 24-75) and 26 of 30 patients (86.7%) had received prior cranial radiotherapy. In the 22 patients with BMs evaluable for response, 7 partial responses (31.8%) and 6 disease stabilizations (27.3%) were observed. Overall, the median brain-specific progression-free survival was 5.6 months (95% confidence interval 4.4-6.8). Patients treated with LC had a median overall survival (from the time of development of BMs) significantly longer compared with 23 patients treated with trastuzumab-based therapies only beyond brain progression (27.9 months versus 16.7 months, respectively, P = 0.01). CONCLUSIONS: LC is active for BMs from HER2+ BC in patients not pretreated with either lapatinib or capecitabine. The introduction of LC after the development of BMs may further improve survival compared with trastuzumab-based therapies only beyond brain progression.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Encefálicas/secundario , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Receptor ErbB-2/metabolismo , Adulto , Anciano , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados , Antineoplásicos/uso terapéutico , Encéfalo/patología , Neoplasias Encefálicas/terapia , Neoplasias de la Mama/metabolismo , Capecitabina , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/análogos & derivados , Humanos , Estimación de Kaplan-Meier , Lapatinib , Persona de Mediana Edad , Quinazolinas/administración & dosificación , Estudios Retrospectivos , Trastuzumab , Resultado del Tratamiento , Adulto JovenRESUMEN
Background: The RESORT trial showed no longer relapse free survival (RFS) with sorafenib following radical metastasectomy in metastatic renal cell carcinoma. We present the updated 42-month follow-up data.Methods: The phase II RESORT trial randomized patients to sorafenib or observation within 12 weeks from surgery. RFS was the primary endpoint.Results: We analyzed 68 patients (32 in sorafenib and 36 in the observation arm), randomized between November 2012 and November 2017. Eighty-one percent in the sorafenib arm and 80% in the observation arm had one metastasis . At a median follow-up of 42 months (interquartile range 31-58), in the observation arm the median RFS was 35 months, RFS probability was 57% (95% CI 42-76%) at 24 and 44% (95% CI 30-65%) at 48 months. In the sorafenib arm, median RFS was 21 months, RFS probability was 50% (95% CI 34-71%) at 24 and 32% (95% CI 18-57%) at 48 months (p = 0.342;HR 1.35;95% CI 0.72-2.54). Forty-seven percent and 37.5% of the patients in the two arms, respectively, are disease free. The site of relapses was independent of the previous metastasectomy site.Expert commentary: Sorafenib after metastasectomy did not improve RFS, but surgery in selected patients should be considered in order to potentially improve survival.Clinical trial registration: www.clinicaltrials.gov identifier is NCT0144480.
Asunto(s)
Carcinoma de Células Renales/terapia , Neoplasias Renales/terapia , Metastasectomía/métodos , Sorafenib/administración & dosificación , Antineoplásicos/administración & dosificación , Carcinoma de Células Renales/patología , Supervivencia sin Enfermedad , Estudios de Seguimiento , Humanos , Neoplasias Renales/patología , Recurrencia Local de Neoplasia , ProbabilidadRESUMEN
BACKGROUND: The current standard first-line treatment of human epidermal growth factor receptor 2 (HER2)-positive (+) metastatic breast cancer is the combination of pertuzumab, trastuzumab and a taxane (P + T + taxane), while standard second-line is ado-trastuzumab-emtansine (T-DM1). The registration trial of pertuzumab, however, did not include early-relapsing patients, defined as patients experiencing tumor relapse ≤12 months from the end of (neo)adjuvant anti-HER2 therapy. Conversely, the pivotal trial of T-DM1 included some patients relapsing ≤6 months after the end of (neo)adjuvant trastuzumab. Thus, a proportion of early-relapsing patients are currently eligible to receive T-DM1 as first-line treatment. Nevertheless, no direct comparison exists between the two regimens in this clinical setting. PATIENTS AND METHODS: We retrospectively compared T-DM1 versus P + T + taxane as first-line treatment in two cohorts of early-relapsing patients in an Italian 'real-world' setting, involving 14 public health care institutions. The primary endpoint was progression-free survival. Secondary endpoints included patients' characterization, overall survival and post-progression survival. Univariate and multivariate analyses were carried out. All tests were two-sided and a P ≤ 0.05 was considered statistically significant. RESULTS: Among 1252 screened patients, 75 met the inclusion criteria. Forty-four (58.7%) received P + T + taxane and 31 (41.3%) received T-DM1. The two cohorts showed similar characteristics of aggressiveness and no significant differences in treatment history. T-DM1, compared with P + T + taxane was associated with worse progression-free survival (adjusted hazard ratio: 2.26, 95% confidence interval: 1.13-4.52, P = 0.021) and overall survival (adjusted hazard ratio: 3.95, 95% confidence interval: 1.38-11.32, P = 0.010), irrespective of previous (neo)adjuvant treatment, age, hormone receptors status, time-to-relapse (≤6 months or within 6-12 months) and presence of visceral/brain metastases. No differences were observed in post-progression survival (P = 0.095). CONCLUSIONS: Our study suggests superiority for P + T + taxane over T-DM1 as up-front treatment of early-relapsing HER2+ metastatic breast cancer, which merits further assessment in larger and prospective trials.
Asunto(s)
Neoplasias de la Mama , Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Femenino , Humanos , Italia , Recurrencia Local de Neoplasia/tratamiento farmacológico , Estudios Prospectivos , Receptor ErbB-2/genética , Receptor ErbB-2/uso terapéutico , Estudios Retrospectivos , Taxoides/uso terapéutico , Trastuzumab/uso terapéuticoRESUMEN
BACKGROUND: We assessed the effectiveness of cetuximab plus chronomodulated irinotecan, 5-fluorouracil (5-FU), leucovorin (FA) and oxaliplatin (L-OHP) (chrono-IFLO) administered as neoadjuvant chemotherapy to increase the resectability of colorectal liver metastases. METHODS: This was a phase II prospective trial with rate of liver metastases resection as primary end point. Forty-three patients with unresectable metastases were enroled: 9 with metastases >5 cm; 29 with multinodular (>4) disease; 1 with hilar location; 4 with extrahepatic lung disease. Treatment consisted of cetuximab at day 1 plus chronomodulated irinotecan 5-FU, FA and L-OHP for 2-6 days every 2 weeks. After the first 17 patients, doses were reduced for irinotecan to 110 mg m⻲, 5-FU to 550 mg m⻲ per day and L-OHP to 15 mg m⻲ per day. RESULTS: Macroscopically complete resections were performed in 26 out of 43 patients (60%) after a median of 6 (range 3-15) cycles. Partial response was noticed in 34 patients (79%). Median overall survival was 37 months (95% CI: 21-53 months), with a 2-year survival of 68% in the entire population, 80.6% in resected patients and 47.1% in unresected patients (P=0.01). Grade 3/4 diarrhoea occurred in 93% and 36% of patients before and after dose reduction. CONCLUSION: Cetuximab plus chrono-IFLO achieved 60% complete resectability of colorectal liver metastases.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/secundario , Neoplasias Hepáticas/patología , Terapia Neoadyuvante/métodos , Adulto , Anciano , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Camptotecina/administración & dosificación , Camptotecina/análogos & derivados , Cetuximab , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/cirugía , Diarrea/inducido químicamente , Supervivencia sin Enfermedad , Receptores ErbB/metabolismo , Femenino , Fluorouracilo/administración & dosificación , Hepatectomía , Humanos , Irinotecán , Leucovorina/administración & dosificación , Masculino , Persona de Mediana Edad , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino , Proyectos de Investigación , Tasa de Supervivencia , Tomografía Computarizada por Rayos XRESUMEN
Ribonucleotide reductase 1 (RRM1) is a determinant of gemcitabine efficacy in non-small-cell lung cancer and pancreatic cancer. We investigated the protein levels of RRM1 and two other DNA repair enzymes, ERCC1 and BRCA1, in 55 metastatic breast cancer (MBC) patients undergoing gemcitabine-based chemotherapy. With automated in situ protein quantification (AQUA v1.6), the average scores for RRM1, ERCC1, and BRCA1 ranged from 245.6-2774.1, 74.0-410.3, and 54.4-1833.1, respectively. They were significantly associated with each other (Spearman's rho > or = .36; p < or = .007). Given their pattern of distribution, RRM1 and BRCA1 are potentially suitable markers for clinical decision making in MBC.
Asunto(s)
Proteína BRCA1/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Proteínas de Unión al ADN/metabolismo , Desoxicitidina/análogos & derivados , Endonucleasas/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Adulto , Anciano , Biomarcadores de Tumor/metabolismo , Desoxicitidina/uso terapéutico , Humanos , Persona de Mediana Edad , Metástasis de la Neoplasia , Ribonucleósido Difosfato Reductasa , GemcitabinaRESUMEN
OBJECTIVE: The phosphatase and tensine homologue gene (PTEN) plays a crucial role in proliferation and survival of cancer cells by antagonizing the function of phosphatidylinositol 3'-kinase (PI3K), which, in turn, results in decreased Akt activity. We investigated the clinical impact of the expression of PTEN, p-Akt and PI3K in HER2-positive metastatic breast cancer (MBC) patients treated with trastuzumab-based therapies. METHODS: Seventy-three patients treated with trastuzumab-based therapies were included and followed prospectively. PTEN, p-Akt and PI3K expression was determined by immunohistochemistry. RESULTS: PTEN, p-Akt and PI3K resulted positive in 48%, 71% and 46.5% of patients, respectively. A significant correlation between PTEN and p-Akt (kappa 0.22, p = 0.03) and p-Akt and PI3K (kappa 0.20, p = 0.05) was observed. PTEN-positive patients had a progression-free survival (PFS) longer than PTEN-negative ones (p = 0.06). When grouped together, patients co-expressing PTEN and p-Akt had a statistically significant longer PFS as compared to the rest of patients (p = 0.01). At the multivariate analysis, PTEN and p-Akt co-expression was an independent predictor of lower risk of progression (hazard ratio 0.53, p = 0.05). CONCLUSION: In HER2-positive MBC, basal co-expression of PTEN and p-Akt might identify those patients who are more likely to benefit from trastuzumab-based therapies.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/genética , Fosfohidrolasa PTEN/genética , Proteínas Proto-Oncogénicas c-akt/genética , Receptor ErbB-2/genética , Adolescente , Anciano , Anticuerpos Monoclonales Humanizados , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Progresión de la Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Metástasis de la Neoplasia/patología , Fosfohidrolasa PTEN/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Receptor ErbB-2/metabolismo , TrastuzumabRESUMEN
BACKGROUND: Based on the efficacy of pegylated liposomal doxorubicin (PLD) in relapsed ovarian cancer, we are conducting a phase III study comparing carboplatin plus either paclitaxel or PLD as first-line therapy in advanced ovarian cancer. Because of limited phase I and II data on PLD plus carboplatin in this setting, we conducted an interim activity analysis. PATIENTS AND METHODS: Patients with stage 1c-IV epithelial ovarian cancer were randomized to carboplatin AUC 5 plus either paclitaxel 175 mg/m(2) or PLD 30 mg/m(2) every 3 weeks for 6 cycles. The interim activity analysis was planned according to a single-stage phase II design with an auspicated 50% response rate; 50 patients eligible for response assessment were required. Response was defined according to RECIST (Response Evaluation Criteria in Solid Tumors). RESULTS: A complete response was achieved in 14 patients (28%) and a partial response in 20 (40%), which produced an overall response rate of 68%. The activity exceeded the minimum required for study continuation. Stable disease was reported in an additional 10 patients (20%). CONCLUSIONS: The adopted schedule of PLD plus carboplatin demonstrates activity as a first-line treatment for advanced ovarian cancer.
Asunto(s)
Antibióticos Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carboplatino/uso terapéutico , Doxorrubicina/análogos & derivados , Neoplasias Glandulares y Epiteliales/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Paclitaxel/uso terapéutico , Polietilenglicoles/uso terapéutico , Adulto , Anciano , Antineoplásicos/uso terapéutico , Área Bajo la Curva , Carboplatino/administración & dosificación , Doxorrubicina/administración & dosificación , Doxorrubicina/uso terapéutico , Femenino , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Glandulares y Epiteliales/mortalidad , Neoplasias Glandulares y Epiteliales/patología , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/patología , Paclitaxel/administración & dosificación , Polietilenglicoles/administración & dosificación , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
Young people (40 years of age) with colorectal cancer (CRC) represent a distinct subgroup with more aggressive disease behaviour compared to older patients. We evaluate whether p53 and bcl-2 could be useful in identifying young patients at higher risk of tumour progression. We reviewed 1340 CRC patients with 58 patients 40 years (4.2%). They had more frequent moderately or poorly differentiated mucinous adenocarcinomas (26% versus 12.3%, p=0.03); higher advanced stage at diagnosis; shorter 5-year overall survival (49.8% versus 71%; p=0.02); more frequent p53 positive (89.8% versus 72.6%, p<0.05) and bcl-2 negative (88.0% versus 66.2%, p<0.05) tumours; no difference in DNA content or proliferation indexes. Moreover, p53+ and bcl-2- resulted in being independent predictors of survival with shorter survival for the p53+/bcl-2- patients. Combining p53 and bcl-2, we could identify young CRC patients at higher risk of progression, who probably require development of a more sophisticated therapeutic approach based on identification of predictive factors.
Asunto(s)
Neoplasias Colorrectales/mortalidad , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Apoptosis/fisiología , Transformación Celular Neoplásica/patología , Distribución de Chi-Cuadrado , Neoplasias Colorrectales/patología , Femenino , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Antígeno Ki-67/metabolismo , Masculino , Persona de Mediana EdadRESUMEN
Metastases to the bones of the hands and feet (acrometastases) represent an uncommon site of recurrence of renal cell carcinoma (RCC). Although challenging, the prompt recognition of solitary acrometastasis from RCC is of crucial importance, since surgical resection of the acrometastasis in the absence of active systemic disease has been reported as beneficial for a subgroup of patients with RCC. Here, we report the case of a patient with RCC metastatic to the left index finger treated with surgical resection of the acrometastasis who shortly thereafter developed progressive disease despite such an aggressive surgical approach.
Asunto(s)
Neoplasias Óseas/secundario , Carcinoma de Células Renales/secundario , Mano , Neoplasias Renales/patología , Anciano , Huesos/patología , Huesos/cirugía , Carcinoma de Células Renales/patología , Mano/cirugía , Humanos , MasculinoRESUMEN
Our aim was to determine the aneusomy level and the HER-2 gene copy numbers, by fluorescence in situ hybridization (FISH) and to analyze their impact on the amplification rate in breast carcinomas considered HER-2 weakly positive cases by immunohistochemistry. We evaluated 343 breast carcinomas using double colour FISH (LSI Her-2/neu gene and CEP 17). Monosomy and polysomy were demonstrated in 24.2% and 46.1% respectively and 101/343 (29.6%) of the specimens were amplified by FISH. A statistically significant difference was observed, when we compared the amplification percentage in polysomic and monosomic specimens (P<0.0001) and, among polysomic specimens, when tumours were compared with HER-2 gene signals number per cell between 3 and 10 and >10 respectively (P<0.0001). Logistic regression analysis showed that HER-2 signals >10 and polysomy absence were independently associated with amplification. Our results confirm that the majority of 2+ IHC cases express the HER-2 protein without gene amplification and highlight the effect of chromosome 17 aneusomy and the HER-2 gene copy number on amplification.
Asunto(s)
Neoplasias de la Mama/genética , Aberraciones Cromosómicas , Genes erbB-2 , Receptor ErbB-2/genética , Amplificación de Genes , Dosificación de Gen , Humanos , Inmunohistoquímica , Ploidias , Análisis de RegresiónRESUMEN
A phase II study was initiated in March 1987 at the Regina Elena National Cancer Institute of Rome to evaluate the efficacy of alternating intraperitoneal (IP) recombinant alpha-2-interferon (r-alpha 2-IFN) and cisplatin (DDP) as salvage therapy for less than or equal to 5 mm residual-disease (RD) ovarian carcinoma. Fourteen assessable patients entered the study. All had received prior chemotherapy (11 with DDP-based regimens); five patients had macroscopic RD (less than or equal to 5 mm), and nine had microscopic RD (histologically positive random biopsies and/or positive cytology and immunocytochemical tests). The response to IP immunochemotherapy was evaluated by laparotomy. Pathologic complete remissions (PCRs) were achieved in seven patients (50%) who have remained free of disease with a median follow-up of 22+ months (range, 11+ to 30+ months). Six patients achieved a stable disease and one presented disease progression. With the exception of chemical peritonitis-induced adhesions, no limiting toxicity was observed. The results obtained in this small, highly selected series demonstrate that a high PCR rate may be obtained with IP immunochemotherapy with DDP and r-alpha 2-IFN as salvage therapy in residual ovarian carcinoma less than or equal to 5 mm after first-line chemotherapy also including intravenous (IV) DDP. Larger comparative studies must be conducted to establish the potential role of IP DDP and r-alpha 2-IFN as compared with either of the single treatments.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Ováricas/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidad , Cisplatino/administración & dosificación , Cisplatino/toxicidad , Ensayos Clínicos como Asunto , Evaluación de Medicamentos , Femenino , Humanos , Infusiones Parenterales , Interferón Tipo I/administración & dosificación , Interferón Tipo I/toxicidad , Persona de Mediana Edad , Proyectos Piloto , Proteínas RecombinantesRESUMEN
Between May 1981 and December 1987, 152 consecutive patients with locally advanced and previously untreated head and neck squamous cell cancer (HNSCC) received two or three courses of neoadjuvant chemotherapy (NAC) prior to surgery and/or radiotherapy. Eighteen percent of patients achieved a complete response and 45% a partial response (PR), for an overall response rate of 63%. A variety of pretreatment patient and tumor characteristics were analyzed for both the tumor response to NAC and survival rate. Significantly higher CR rates were found in patients with a World Health Organization (WHO) performance status (PS) of 0 to 1 than in those patients with a PS of 2 (P = .03). Patients with stage III disease were significantly more likely to respond than those with stage IV (P = .006). Evaluation of all parameters through multivariate analysis identifies the tumor classification (P = .001) and the primary site (P = .006) as the most significant in predicting CR. The overall 5-year survival rate of the entire group of patients was 18% (median survival, 14.3 months). Analysis by PS (P = .001), stage (P = .002), and tumor (P = .001), and node (P = .01) classes showed significant differences. Patients achieving a CR after NAC had a significantly improved survival rate as compared with those with residual disease at assessment (P = .0003). With the multistep regression analysis, the tumor (P = .005) and node (P = .007) classifications, and the sex (P = .03) were significant factors, but CR (P = .0004) remained the most important and independent predictive factor. Randomized prospective trials are requested to clearly establish the role of NAC on survival rates.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Escamosas/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Adulto , Anciano , Bleomicina/administración & dosificación , Carcinoma de Células Escamosas/mortalidad , Cisplatino/administración & dosificación , Ensayos Clínicos como Asunto , Terapia Combinada , Femenino , Fluorouracilo/administración & dosificación , Neoplasias de Cabeza y Cuello/mortalidad , Humanos , Masculino , Metotrexato/administración & dosificación , Persona de Mediana Edad , Premedicación , Pronóstico , Vincristina/administración & dosificaciónRESUMEN
Ondansetron (OND) is a new 5-HT3 receptor antagonist that give complete protection from emesis/nausea in approximately 50% of cisplatin (CDDP)-treated patients. To evaluate if dexamethasone (DEX) added to OND increases antiemetic efficacy, we carried out a double-blind randomized crossover study to compare the antiemetic activity of OND with OND plus DEX. One hundred two chemotherapy-naive patients (44 women and 58 men) scheduled to receive CDDP chemotherapy at doses greater than or equal to 50 mg/m2 entered the study. Eighty-nine patients completed both cycles with the following results: complete protection from emesis/nausea was obtained in 57/59 patients (64.0%/66.3%) with OND and in 81/79 (91.0%/88.8%) with OND plus DEX (P = .0005/P = .0021). At the end of the study, 53% of the patients expressed a treatment preference, and of these, 74% chose OND plus DEX compared with 26% who preferred OND alone, a statistically significant difference (P less than .003). Side effects were very mild and not significantly different between the two treatments. We conclude that OND plus DEX is more efficacious than OND in protecting patients from CDDP-induced emesis and nausea.