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1.
ESMO Open ; 8(4): 101598, 2023 08.
Article in English | MEDLINE | ID: mdl-37467658

ABSTRACT

BACKGROUND: The treatment of patients with brain-spread renal cell carcinoma (RCC) is an unmet clinical need, although more recent therapeutic strategies have significantly improved RCC patients' life expectancy. Our multicenter, retrospective, observational study investigated a real-world cohort of patients with brain metastases (BM) from RCC (BMRCC). PATIENTS AND METHODS: A total of 226 patients with histological diagnosis of RCC and radiological evidence of BM from 22 Italian institutions were enrolled. Univariate and multivariate models were performed to investigate the impact of clinicopathological features and multimodal treatments on both overall survival (OS) from the BM diagnosis and intracranial progression-free survival (iPFS). RESULTS: The median OS from the BM diagnosis was 18.8 months (interquartile range: 6.2-43 months). Multivariate analysis confirmed the following as positive independent prognostic factors: a Karnofsky Performance Status >70% [hazard ratio (HR) = 0.49, 95% confidence interval (CI) 0.26-0.92, P = 0.0026] and a single BM (HR = 0.51, 95% CI 0.31-0.86, P = 0. 0310); in contrast, the following were confirmed as worse prognosis factors: progressive extracranial disease (HR = 1.66, 95% CI 1.003-2.74, P = 0.00181) and only one line of systemic therapy after the BM occurrence (HR = 2.98, 95% CI 1.62-5.49, P = 0.029). Subgroup analyses showed no difference in iPFS according to the type of the first systemic treatment [immunotherapy (IT) or targeted therapy (TT)] carried out after the BM diagnosis (HR = 1.033, 95% CI 0.565-1.889, P = 0.16), and revealed that external radiation therapy (eRT) significantly prolonged iPFS when combined with IT (10.7 months, 95% CI 4.9-48 months, P = 0.0321) and not when combined with TT (9.01 months, 95% CI 2.7-21.2 months, P = 0.59). CONCLUSIONS: Our results suggest a potential additive effect in terms of iPFS for eRT combined with IT and encourage a more intensive multimodal therapeutic strategy in a multidisciplinary context to improve the survival of BMRCC patients.


Subject(s)
Brain Neoplasms , Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Carcinoma, Renal Cell/therapy , Kidney Neoplasms/therapy , Kidney Neoplasms/pathology , Retrospective Studies , Prognosis , Brain Neoplasms/therapy , Brain Neoplasms/secondary
2.
Crit Rev Oncol Hematol ; 146: 102864, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31986318

ABSTRACT

Chemotherapeutic agents (docetaxel, cabazitaxel), hormonal therapies (abiraterone, enzalutamide) and radium-223 improve survival in patients with bone metastatic castration-resistant prostate cancer (mCRPC). Combinations of radium-223 with these agents or novel drugs have been investigated in order to improve survival and decrease bone-related morbidity. In mCRPC, clinical and preclinical data indicate that radium-223, abiraterone and enzalutamide have a direct effect on prostate cancer cells and bone microenvironment when administered as single agents. Initial results from studies of radium-223 and abiraterone, enzalutamide or docetaxel demonstrated efficacy without any safety concern in pre-treated mCRPC; however, this safety profile changed when radium-based combination therapies were administered in un-pretreated mCRPC. This review underline the biological rationale for combining radium strategies, investigating their effects on bone in terms of control of skeletal-related events and bone disease progression. The aim is to understand the possible reasons why different radium-based combination treatments can led to different clinical outcomes.


Subject(s)
Antineoplastic Agents/therapeutic use , Bone Density Conservation Agents/therapeutic use , Bone Neoplasms/pathology , Bone Neoplasms/therapy , Prostatic Neoplasms, Castration-Resistant/pathology , Prostatic Neoplasms, Castration-Resistant/therapy , Radiopharmaceuticals/administration & dosage , Radiopharmaceuticals/therapeutic use , Radium/therapeutic use , Androstenes/therapeutic use , Benzamides , Bone Neoplasms/secondary , Docetaxel/therapeutic use , Humans , Male , Nitriles , Orchiectomy , Phenylthiohydantoin/analogs & derivatives , Phenylthiohydantoin/therapeutic use , Radioisotopes/therapeutic use , Treatment Outcome , Tumor Microenvironment
3.
Ann Oncol ; 29(4): 924-930, 2018 04 01.
Article in English | MEDLINE | ID: mdl-29324972

ABSTRACT

Background: Neutrophil/lymphocyte ratio (NLR), defined as absolute neutrophils count divided by absolute lymphocytes count, has been reported as poor prognostic factor in several neoplastic diseases but only a few data are available about unresectable metastatic colorectal cancer (mCRC) patients (pts). The aim of our study was to evaluate the prognostic and predictive role of NLR in the TRIBE trial. Patients and methods: Pts enrolled in TRIBE trial were included. TRIBE is a multicentre phase III trial randomizing unresectable and previously untreated mCRC pts to receive FOLFOXIRI or FOLFIRI plus bevacizumab. A cut-off value of 3 was adopted to discriminate pts with low (NLR < 3) versus high (NLR ≥ 3) NLR, as primary analysis. As secondary analysis, NLR was treated as an ordinal variable with three levels based on terciles distribution. Results: NLR at baseline was available for 413 patients. After multiple imputation at univariate analysis, patients with high NLR had significantly shorter progression-free survival (PFS) [hazard ratio (HR) 1.27 (95% CI 1.05-1.55), P = 0.017] and overall survival (OS) [HR 1.56 (95% CI 1.25-1.95), P < 0.001] than patients with low NLR. In the multivariable model, NLR retained a significant association with OS [HR 1.44 (95% CI 1.14-1.82), P = 0.014] but not with PFS [HR 1.18 (95% CI 0.95-1.46), P = 0.375]. No interaction effect between treatment arm and NLR was evident in terms of PFS (P for interaction = 0.536) or OS (P for interaction = 0.831). Patients with low [HR 0.84 (95% CI 0.64-1.08)] and high [HR 0.73 (95% CI 0.54-0.97)] NLR achieved similar PFS benefit from the triplet and consistent results were obtained in terms of OS [HR 0.83 (95% CI 0.62-1.12) for low NLR; HR 0.82 (95% CI 0.59-1.12) for high NLR]. Conclusion: This study confirmed the prognostic role of NLR in mCRC pts treated with bevacizumab plus chemotherapy in the first line, showing the worse prognosis of pts with high NLR. The advantage of the triplet is independent of NLR at baseline.


Subject(s)
Colorectal Neoplasms/blood , Lymphocyte Count , Neoplasm Metastasis , Neutrophils/cytology , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Bevacizumab/administration & dosage , Camptothecin/administration & dosage , Camptothecin/analogs & derivatives , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/pathology , Female , Fluorouracil/administration & dosage , Humans , Leucovorin/administration & dosage , Male , Middle Aged , Organoplatinum Compounds/administration & dosage , Prognosis , Retrospective Studies
4.
Boll Ist Sieroter Milan ; 68(1): 34-41, 1989.
Article in Italian | MEDLINE | ID: mdl-2535244

ABSTRACT

135 subjects, belonging to the sanitary staff and the dialyzed patients (high-risk classes) of the Ospedale Maggiore in Crema, have been vaccinated against hepatitis B with Hevac B vaccine produced by Pasteur firm. We have followed the vaccination protocol advised by the producer firm: subcutaneous administration in the deltoid region of three doses at one month intervals. One year after the third dose a further one was administered. Each dose of vaccine contains 5 micrograms of purified and inactivated HBsAg. We have investigated the presence of HBsAb, as protection standard, using EIA Abbott. 30 days after the first dose, HBsAb was present in 7.3% of the subjects; this percentage increased until 26.5% after the second dose and until 77.7% after the third one. One month after the fourth dose 95.6% appeared serologically protected against HBV. Secondary reactions to vaccine have been negligible.


Subject(s)
Hepatitis B Antibodies/biosynthesis , Hepatitis B/prevention & control , Vaccines, Synthetic/immunology , Viral Hepatitis Vaccines/immunology , Adult , Evaluation Studies as Topic , Hepatitis B Surface Antigens/administration & dosage , Hepatitis B Surface Antigens/immunology , Hepatitis B Vaccines , Hepatitis B virus/immunology , Humans , Middle Aged , Personnel, Hospital , Renal Dialysis , Risk Factors , Vaccines, Synthetic/administration & dosage , Viral Hepatitis Vaccines/administration & dosage
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