Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 10 de 10
Filtrar
1.
Lancet ; 404(10459): 1227-1239, 2024 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-39293462

RESUMEN

BACKGROUND: [177Lu]Lu-PSMA-617 (177Lu-PSMA-617) prolongs radiographic progression-free survival and overall survival in patients with metastatic castration-resistant prostate cancer previously treated with androgen receptor pathway inhibitor (ARPI) and taxane therapy. We aimed to investigate the efficacy of 177Lu-PSMA-617 in patients with taxane-naive metastatic castration-resistant prostate cancer. METHODS: In this phase 3, randomised, controlled trial conducted at 74 sites across Europe and North America, taxane-naive patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer who had progressed once on a previous ARPI were randomly allocated (1:1) to open-label, intravenous 177Lu-PSMA-617 at a dosage of 7·4 GBq (200 mCi) ± 10% once every 6 weeks for six cycles, or a change of ARPI (to abiraterone or enzalutamide, administered orally on a continuous basis per product labelling). Crossover from ARPI change to 177Lu-PSMA-617 was allowed after centrally confirmed radiographic progression. The primary endpoint was radiographic progression-free survival, defined as the time from randomisation until radiographic progression or death, assessed in the intention-to-treat population. Safety was a secondary endpoint. This study is registered with ClinicalTrials.gov (NCT04689828) and is ongoing. In this primary report of the study, we present primary (first data cutoff) and updated (third data cutoff) analyses of radiographic progression-free survival; all other data are based on the third data cutoff. FINDINGS: Overall, of the 585 patients screened, 468 met all eligibility criteria and were randomly allocated between June 15, 2021 and Oct 7, 2022 to receive 177Lu-PSMA-617 (234 [50%] patients) or ARPI change (234 [50%]). Baseline characteristics were mostly similar between groups; median number of 177Lu-PSMA-617 cycles was 6·0 (IQR 4·0-6·0). Of patients assigned to ARPI change, 134 (57%) crossed over to receive 177Lu-PSMA-617. In the primary analysis (median time from randomisation to first data cutoff 7·26 months [IQR 3·38-10·55]), the median radiographic progression-free survival was 9·30 months (95% CI 6·77-not estimable) in the 177Lu-PSMA-617 group versus 5·55 months (4·04-5·95) in the ARPI change group (hazard ratio [HR] 0·41 [95% CI 0·29-0·56]; p<0·0001). In the updated analysis at time of the third data cutoff (median time from randomisation to third data cutoff 24·11 months [IQR 20·24-27·40]), median radiographic progression-free survival was 11·60 months (95% CI 9·30-14·19) in the 177Lu-PSMA-617 group versus 5·59 months (4·21-5·95) in the ARPI change group (HR 0·49 [95% CI 0·39-0·61]). The incidence of grade 3-5 adverse events was lower in the 177Lu-PSMA-617 group (at least one event in 81 [36%] of 227 patients; four [2%] grade 5 [none treatment related]) than the ARPI change group (112 [48%] of 232; five [2%] grade 5 [one treatment related]). INTERPRETATION: 177Lu-PSMA-617 prolonged radiographic progression-free survival relative to ARPI change, with a favourable safety profile. For patients with PSMA-positive metastatic castration-resistant prostate cancer who are being considered for a change of ARPI after progression on a previous ARPI, 177Lu-PSMA-617 may be an effective treatment alternative. FUNDING: Novartis.


Asunto(s)
Androstenos , Dipéptidos , Compuestos Heterocíclicos con 1 Anillo , Lutecio , Nitrilos , Feniltiohidantoína , Neoplasias de la Próstata Resistentes a la Castración , Humanos , Masculino , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/patología , Compuestos Heterocíclicos con 1 Anillo/uso terapéutico , Anciano , Lutecio/uso terapéutico , Androstenos/uso terapéutico , Dipéptidos/uso terapéutico , Feniltiohidantoína/uso terapéutico , Nitrilos/uso terapéutico , Antagonistas de Receptores Androgénicos/uso terapéutico , Persona de Mediana Edad , Benzamidas/uso terapéutico , Taxoides/uso terapéutico , Antígeno Prostático Específico/sangre , Radioisótopos/uso terapéutico , Supervivencia sin Progresión
2.
N Engl J Med ; 386(12): 1132-1142, 2022 03 24.
Artículo en Inglés | MEDLINE | ID: mdl-35179323

RESUMEN

BACKGROUND: Darolutamide is a potent androgen-receptor inhibitor that has been associated with increased overall survival among patients with nonmetastatic, castration-resistant prostate cancer. Whether a combination of darolutamide, androgen-deprivation therapy, and docetaxel would increase survival among patients with metastatic, hormone-sensitive prostate cancer is unknown. METHODS: In this international, phase 3 trial, we randomly assigned patients with metastatic, hormone-sensitive prostate cancer in a 1:1 ratio to receive darolutamide (at a dose of 600 mg [two 300-mg tablets] twice daily) or matching placebo, both in combination with androgen-deprivation therapy and docetaxel. The primary end point was overall survival. RESULTS: The primary analysis involved 1306 patients (651 in the darolutamide group and 655 in the placebo group); 86.1% of the patients had disease that was metastatic at the time of the initial diagnosis. At the data cutoff date for the primary analysis (October 25, 2021), the risk of death was significantly lower, by 32.5%, in the darolutamide group than in the placebo group (hazard ratio 0.68; 95% confidence interval, 0.57 to 0.80; P<0.001). Darolutamide was also associated with consistent benefits with respect to the secondary end points and prespecified subgroups. Adverse events were similar in the two groups, and the incidences of the most common adverse events (occurring in ≥10% of the patients) were highest during the overlapping docetaxel treatment period in both groups. The frequency of grade 3 or 4 adverse events was 66.1% in the darolutamide group and 63.5% in the placebo group; neutropenia was the most common grade 3 or 4 adverse event (in 33.7% and 34.2%, respectively). CONCLUSIONS: In this trial involving patients with metastatic, hormone-sensitive prostate cancer, overall survival was significantly longer with the combination of darolutamide, androgen-deprivation therapy, and docetaxel than with placebo plus androgen-deprivation therapy and docetaxel, and the addition of darolutamide led to improvement in key secondary end points. The frequency of adverse events was similar in the two groups. (Funded by Bayer and Orion Pharma; ARASENS ClinicalTrials.gov number, NCT02799602.).


Asunto(s)
Antagonistas de Receptores Androgénicos/uso terapéutico , Neoplasias de la Próstata/tratamiento farmacológico , Pirazoles/uso terapéutico , Anciano , Anciano de 80 o más Años , Antagonistas de Andrógenos/uso terapéutico , Antagonistas de Receptores Androgénicos/efectos adversos , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Docetaxel/efectos adversos , Docetaxel/uso terapéutico , Quimioterapia Combinada , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia/tratamiento farmacológico , Neutropenia/inducido químicamente , Modelos de Riesgos Proporcionales , Neoplasias de la Próstata/mortalidad , Neoplasias de la Próstata/patología , Neoplasias de la Próstata Resistentes a la Castración , Pirazoles/efectos adversos
3.
Cancer Metastasis Rev ; 31 Suppl 1: S19-27, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22821550

RESUMEN

Treatment options for metastatic renal cell carcinoma (mRCC) have evolved very rapidly, as reflected by the approval of the many drugs that have shown efficacy in phase III studies. Approved drugs include tyrosine kinase inhibitors (TKI) such as sunitinib, sorafenib and pazopanib, vascular endothelial growth factor inhibitors such as bevacizumab, and mammalian target of rapamycin (mTOR) inhibitors such as temsirolimus and everolimus. These biological agents have toxicity profiles that differ from those accompanying current chemotherapeutic agents, but their novelty leads to a lack of exhaustive clinical data regarding related adverse events (AEs), whose symptoms may overlap with those of the chronic illnesses of patients with mRCC such as hypertension, hyperglycemia, and pneumonitis. Hypertension, hypothyroidism, hand-foot syndrome, and fatigue are AEs frequently associated with TKIs; whereas immunosuppression, stomatitis, metabolic alterations, and non-infectious pneumonitis are AEs of mTOR inhibitors. Recommendations for treating these adverse events in patients with mRCC are usually the same as those for the general population. Mild to moderate toxicities may be managed with supportive and pharmacologic interventions, but higher-grade toxicities usually require external specialist consultation, dose reductions, and treatment interruption or discontinuation. Some groups of patients with mRCC, such as frail, elderly patients, and patients with renal or liver dysfunction, require special management of AEs.


Asunto(s)
Antineoplásicos/efectos adversos , Carcinoma de Células Renales/tratamiento farmacológico , Neoplasias Renales/tratamiento farmacológico , Antineoplásicos/uso terapéutico , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/secundario , Humanos , Neoplasias Renales/patología , Metástasis de la Neoplasia
4.
Clin Transl Oncol ; 8(4): 298-300, 2006 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-16648109

RESUMEN

Renal cell carcinoma is an uncommon tumor in adults. Metastasis in the nasal fossa is rare, and can become apparent as a result of repeated epistaxis. We report a patient with renal cell carcinoma presenting with epistaxis secondary to a metastasis in the right nasal fossa. The primary tumor was treated with nephrectomy and the nasal fossa metastasis was treated successfully with embolization, chemoimmunotherapy, surgery, and radiotherapy. The presence of repeated epistaxis may very occasionally be the first symptom of renal cell carcinoma, and systemic treatment combined with local treatment may enable adequate control of the disease.


Asunto(s)
Adenocarcinoma de Células Claras/secundario , Carcinoma de Células Renales/secundario , Neoplasias Renales/diagnóstico , Cavidad Nasal , Neoplasias Nasales/secundario , Adenocarcinoma de Células Claras/patología , Adenocarcinoma de Células Claras/terapia , Antimetabolitos Antineoplásicos/uso terapéutico , Antineoplásicos Fitogénicos/uso terapéutico , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/terapia , Terapia Combinada , Embolización Terapéutica , Epistaxis/etiología , Resultado Fatal , Fluorouracilo/uso terapéutico , Humanos , Factores Inmunológicos/uso terapéutico , Interferón alfa-2 , Interferón-alfa/uso terapéutico , Interleucina-2/uso terapéutico , Neoplasias Renales/patología , Neoplasias Renales/terapia , Neoplasias Pulmonares/secundario , Neoplasias Pulmonares/cirugía , Escisión del Ganglio Linfático , Masculino , Persona de Mediana Edad , Nefrectomía , Neoplasias Nasales/diagnóstico , Neoplasias Nasales/terapia , Orquiectomía , Neumonectomía/métodos , Radioterapia Adyuvante , Proteínas Recombinantes , Neoplasias Testiculares/secundario , Neoplasias Testiculares/cirugía , Tomografía Computarizada por Rayos X , Vinblastina/uso terapéutico
5.
Clin Transl Oncol ; 8(10): 742-9, 2006 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-17074673

RESUMEN

UNLABELLED: Objective. We conducted this phase II trial to evaluate the efficacy and toxicity of the sequential nonplatinum combination chemotherapy consisting of gemcitabine (GEM) and vinorelbine (VNR) followed by weekly docetaxel (DOC) in patients with advanced non-small-cell lung cancer (NSCLC). Patients and methods. ELIGIBILITY CRITERIA: stage IV NSCLC, Performance status =/< 2, adequate renal, hepatic and bone marrow function. Treatment consisted on: VNR 25 mg/m(2) plus gemcitabine 1000 mg/m(2), on days 1 and 8 of each 21-day cycle, followed by docetaxel 36 mg/m(2) weekly until progression or unacceptable toxicity. Results. 21 stage IV patients were enrolled. All patients are evaluable for treatment response and toxicity profile. The mean age of the patients was 63 years (range: 51 to 72) with 18 (86%) males and 3 (14%) females. Histology types were: adenocarcinoma in 8 patients (38%), large cell carcinoma in 1 patients (5%) and squamous cell carcinoma in 12 patients (57%). The majority of the patients had and ECOG PS of 1. Eight patients (38%) did not complete six cycles of gemcitabine-navelbine. The median number of cycles of gemcitabine-navelbine was 4 (range 2-6) Of the 13 patients (61%) who completed six cycles of gemcitabine-navelbine, all of them went on to receive weekly docetaxel and received at least 3 cycles, with a median number of 8 cycles (range 3- 16). The overall response rate was 33%. Respect survival, the minimum follow-up was 6 months (range, 6-25 months). The median survival time (MST) was 7.9 months, and the 1-year survival was 30%, and the median progression-free survival was 4.7 months. Toxicity was mild, well tolerated and mostly hematologic. In the GEM/VNR cycle, grade 3/4 neutropenia occurred in 14%, two patients with febrile neutropenia. Grade 3 anaemia in 1 patients (5%) and grade 3 thrombocytopenia in 1 patient (5%). Nonhematologic toxicity was also mild: 1 patient with Grade 3 skin toxicity with docetaxel, 1 patient with grade 3 infection, 2 patients with grade 3 astenia and 1 patient with a mild allergic reaction postchemotherapy treatment with docetaxel. Conclusion. The sequential triplet nonplatinum chemotherapy consisted of GEM/VNR followed by weekly DOC is active and can be administered safely in advanced NSCLC. Our results are similar with other sequential regimens and did not represent a significant improvement in the treatment of this disease.


Asunto(s)
Antimetabolitos Antineoplásicos/administración & dosificación , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Desoxicitidina/análogos & derivados , Neoplasias Pulmonares/tratamiento farmacológico , Taxoides/administración & dosificación , Vinblastina/análogos & derivados , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/patología , Anciano , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/patología , Desoxicitidina/administración & dosificación , Docetaxel , Femenino , Estudios de Seguimiento , Humanos , Pulmón/patología , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Análisis de Supervivencia , Factores de Tiempo , Vinblastina/administración & dosificación , Vinorelbina , Gemcitabina
6.
Clin Lung Cancer ; 7(2): 121-6, 2005 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-16179099

RESUMEN

BACKGROUND: In this phase I/II trial, the maximum tolerated dose (MTD) and activity of vinorelbine administered in continuous infusion as first-line treatment for advanced non-small-cell lung cancer (NSCLC) was determined in 25 consecutive chemotherapy-naive patients with advanced NSCLC. PATIENTS AND METHODS: Vinorelbine was administered as an initial intravenous (I.V.) bolus of 8 mg/m(2) on day 1 followed by a 4-day continuous I.V. infusion at 5 different 24-hour dose levels to be repeated every 21 days. All 25 patients (159 cycles) were evaluable for response. The MTD was 8 mg/m(2) bolus followed by a continuous I.V. infusion of 11 mg/m(2) per day over 4 days. RESULTS: The dose-limiting toxicities were febrile neutropenia in 6 patients and grade 3 mucositis in 2 patients. There was less neurotoxicity and constipation and more mucositis compared with the weekly bolus scheme. There was no significant cumulative toxicity after 3 cycles. Treatment responses were observed in 6 patients: 1 complete response and 5 partial responses. The overall response rate was 24% (95% confidence interval [CI], 8%-40%). Median time to progression was 4 months (95% CI, 2-11 months), and median survival was 6 months (95% CI, 2-18 months). CONCLUSION: The results demonstrate that, in this setting of first-line treatment of NSCLC, vinorelbine administered as an 8 mg/m(2) bolus followed by a continuous infusion of 11 mg/m(2) per day over 4 days is the recommended schedule. Further trials are necessary to establish activity and possible benefits of combination with other agents.


Asunto(s)
Antineoplásicos Fitogénicos/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Vinblastina/análogos & derivados , Adenocarcinoma/tratamiento farmacológico , Adulto , Anciano , Antineoplásicos Fitogénicos/efectos adversos , Astenia/inducido químicamente , Carcinoma de Células Grandes/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Células Escamosas/tratamiento farmacológico , Estreñimiento/inducido químicamente , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Infusiones Intravenosas , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Mucositis/inducido químicamente , Estadificación de Neoplasias , Neutropenia/inducido químicamente , Resultado del Tratamiento , Vinblastina/administración & dosificación , Vinblastina/efectos adversos , Vinorelbina
7.
Clin Transl Oncol ; 7(9): 409-12, 2005 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-16238976

RESUMEN

Primary signet-ring cell carcinoma of the prostate is infrequent and even more so as secondary spread of this pathologic sub-type to the prostate. We describe the sixth reported case with a diagnosis of a secondary signet-ring cell tumour of the prostate secondary to a gastric cancer. Five years post-gastrectomy to resect signet-ring cell carcinoma, we detected a secondary intra-prostatic spread with urinary tract obstruction. The physical appearance of the tumour cells was similar to that of the previously-resected signet-cell carcinoma of the stomach. There were no metastases in other sites and the patient was treated with radiotherapy. When confronted with intra-prostatic signet-ring cell adenocarcinoma it is necessary to distinguish between primary and secondary aetiology since this would reflect in the choice of treatment and prognosis.


Asunto(s)
Carcinoma de Células en Anillo de Sello/secundario , Neoplasias de la Próstata/secundario , Neoplasias Gástricas/patología , Carcinoma de Células en Anillo de Sello/diagnóstico , Carcinoma de Células en Anillo de Sello/radioterapia , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/radioterapia
8.
Clin. transl. oncol. (Print) ; Clin. transl. oncol. (Print);8(4): 298-300, abr. 2006. ilus
Artículo en En | IBECS (España) | ID: ibc-047673

RESUMEN

No disponible


Renal cell carcinoma is an uncommon tumor inadults. Metastasis in the nasal fossa is rare, and canbecome apparent as a result of repeated epistaxis.We report a patient with renal cell carcinoma presentingwith epistaxis secondary to a metastasis inthe right nasal fossa. The primary tumor was treatedwith nephrectomy and the nasal fossa metastasiswas treated successfully with embolization, chemoimmunotherapy,surgery, and radiotherapy. Thepresence of repeated epistaxis may very occasionallybe the first symptom of renal cell carcinoma, andsystemic treatment combined with local treatmentmay enable adequate control of the disease


Asunto(s)
Masculino , Persona de Mediana Edad , Humanos , Neoplasias Nasales/secundario , Neoplasias Renales/patología , Carcinoma de Células Renales/patología , Epistaxis/etiología , Metástasis de la Neoplasia/patología
9.
Clin. transl. oncol. (Print) ; Clin. transl. oncol. (Print);8(7): 519-524, jul. 2006. tab
Artículo en En | IBECS (España) | ID: ibc-047706

RESUMEN

No disponible


Backbround. In this Phase I/II trial, the maximumtolerateddose (MTD) and activity of cisplatin plusvinorelbine (VRL) administered in continuous infusionas first-line treatment of advanced non smallcell lung cancer (NSCLC) was determined in 12consecutive chemotherapy-naive patients with advancedNSCLC.Patients and methods. The dose of cisplatin was100 mg/m2 in all patients, and vinorelbine was administeredas an initial intravenous (iv) bolus of 8mg/m2 on day 1 followed by a 4-day continuous ivinfusion at 4 different 24 h dose levels (DLs) to berepeated every 21 days. All 12 patients (47 cycles)were evaluable for response and toxicity.Results. The MTD was 8 mg/m2 bolus followed by acontinuous iv infusion of 8 mg/m2 per day over 4days. The dose limiting toxicities (DLT) were febrileneutropenia in 4 patients and grade 3 mucositis in 1patient. There was less neuro-toxicity and comparedto the weekly bolus scheme. There was nosignificant cumulative toxicity after 3 cycles. Partialresponses were observed in 6 patients; an overall responserate of 50% (95% CI: 30-65%). Median time toprogression was 5,5 months (95% CI: 1,5-11 months)and median survival was 11 months (95% CI: 5-20months).Conclusions. The results demonstrate that, in thissetting of first-line treatment of NSCLC, cisplatinplus vinorelbine at 8 mg/m2 bolus followed by acontinuous infusion of 8 mg/m2 per day over 4 daysis the recommended schedule. Further trials wouldbe useful to establish activity of this combination


Asunto(s)
Humanos , Cisplatino/farmacocinética , Alcaloides de la Vinca/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Infusiones Intravenosas/métodos , Dosis Máxima Tolerada , Protocolos de Quimioterapia Combinada Antineoplásica
10.
Clin. transl. oncol. (Print) ; Clin. transl. oncol. (Print);7(9): 409-412, oct. 2005. ilus
Artículo en En | IBECS (España) | ID: ibc-040797

RESUMEN

Primary signet-ring cell carcinoma of the prostate is infrequent and even more so as secondary spread of this pathologic sub-type to the prostate. We describe the sixth reported case with a diagnosis of a secondary signet-ring cell tumour of the prostate secondary to a gastric cancer. Five years post-gastrectomy to resect signet-ring cell carcinoma, we detected a secondary intra-prostatic spread with urinary tract obstruction. The physical appearance of the tumour cells was similar to that of the pre-viously-resected signet-cell carcinoma of the stomach. There were no metastases in other sites and the patient was treated with radiotherapy. When confronted with intra-prostatic signet-ring cell adenocarcinoma it is necessary to distinguish between primary and secondary aetiology since this would reflect in the choice of treatment and prognosis


Asunto(s)
Masculino , Persona de Mediana Edad , Humanos , Neoplasias Gástricas/complicaciones , Neoplasias de la Próstata/secundario , Neoplasias de la Próstata/patología , Carcinoma de Células en Anillo de Sello/patología
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA