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1.
Gynecol Oncol ; 183: 61-67, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38518529

RESUMO

OBJECTIVE: Recurrent gynecological tumors (e.g., endometrial, and ovarian cancers) are incurable diseases; therefore, new treatment options are urgently needed. The PTEN-AKT-PI3K pathway is frequently altered in these tumors, representing a potential treatment target. Alpelisib is an α-specific PI3K inhibitor approved in PIK3CA-mutated advanced breast cancer. We report outcomes from a large series of patients with PIK3CA-mutated gynecological cancers prospectively treated with alpelisib within a controlled program. METHODS: From April 2021 to December 2022, 36 patients with PIK3CA-mutated advanced gynecological cancers received alpelisib 300 mg orally once daily. Objective response (ORR) and disease control (DCR) rates provided measure of the antitumor activity of alpelisib, the primary objective of the study. RESULTS: Included patients had endometrial (17/36 [47%]), ovarian (10/36 [28%]), or other gynecological cancers (9/36 [25%]). Most patients had received 2-3 prior systemic treatments (endometrial, 47·2%; ovarian, 60%; other, 56%), and presented with visceral metastases at baseline (82%, 70%, and 56%, respectively). Overall, 17 different PIK3CA mutations were found, including 53% in the kinase domain (most commonly H1047R) and 36% in the helical domain (most commonly E545K). Overall, the ORR was 28% and DCR was 61%, with the greatest benefit observed in patients with endometrial cancer (35% and 71%, respectively). CONCLUSION: Alpelisib represents an active treatment option in patients with recurrent gynecological cancers harboring a PIK3CA mutation. These findings support the need of biomarker-driven randomized trials of PI3K inhibitors in gynecological cancers.


Assuntos
Classe I de Fosfatidilinositol 3-Quinases , Neoplasias dos Genitais Femininos , Mutação , Tiazóis , Humanos , Feminino , Classe I de Fosfatidilinositol 3-Quinases/genética , Pessoa de Meia-Idade , Idoso , Neoplasias dos Genitais Femininos/genética , Neoplasias dos Genitais Femininos/tratamento farmacológico , Neoplasias dos Genitais Femininos/patologia , Adulto , Tiazóis/uso terapêutico , Tiazóis/administração & dosagem , Idoso de 80 Anos ou mais , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/patologia , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Estudos Prospectivos , Inibidores de Fosfoinositídeo-3 Quinase/uso terapêutico , Inibidores de Fosfoinositídeo-3 Quinase/administração & dosagem
3.
Recenti Prog Med ; 103(2): 62-5, 2012 Feb.
Artigo em Italiano | MEDLINE | ID: mdl-22430749

RESUMO

Emerging data suggest pemetrexed is active in patients with adenocarcinoma of lung compared to those with squamous cell carcinoma. We retrospectively reviewed advanced non small cell lung cancer (NSCLC) patients previously treated, analysing efficacy on histologic characteristics. From January 2007 to December 2010, 25 patients with stage IIIB or IV NSCLC (17 with adenocarcinoma and 8 with squamous cell carcinoma), who had previously failed on platinum-based chemotherapy, received pemetrexed 500 mg/mq every 3 weeks until disease progression or unacceptable toxicities. Analysing the histologic subgroups we observed 1 (5.9%) complete response, partial response in 5 patients (29.4%), stable disease in 6 (35.3%), progression disease in 5 (29.4%) in adenocarcinoma group compared to 4 (50%) stable disease and 4 (50%) progression disease in squamous cell carcinoma group. Median progression free survival was 8 months (range 3-22) for adenocarcinoma patients and 4 months (range 2-6) for squamous cell patients. According to data of the literature, also our small retrospective study conducted on unselected patients confirms the difference of pemetrexed efficacy by histology type, with better results in patients with adenocarcinoma lung cancer.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Glutamatos/uso terapêutico , Guanina/análogos & derivados , Neoplasias Pulmonares/tratamento farmacológico , Adenocarcinoma/tratamento farmacológico , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/tratamento farmacológico , Intervalo Livre de Doença , Feminino , Seguimentos , Guanina/uso terapêutico , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pemetrexede , Estudos Retrospectivos , Resultado do Tratamento
4.
PLoS One ; 8(10): e74402, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24204569

RESUMO

BACKGROUND: Bone metastasis represents an increasing clinical problem in advanced gastric cancer (GC) as disease-related survival improves. In literature, few data on the natural history of bone disease in GC are available. PATIENTS AND METHODS: Data on clinicopathology, skeletal outcomes, skeletal-related events (SREs), and bone-directed therapies for 208 deceased GC patients with evidence of bone metastasis were statistically analyzed. RESULTS: Median time to bone metastasis was 8 months (CI 95%, 6.125-9.875 months) considering all included patients. Median number of SREs/patient was one. Less than half of the patients (31%) experienced at least one and only 4 and 2% experienced at least two and three events, respectively. Median times to first and second SRE were 2 and 4 months, respectively. Median survival was 6 months after bone metastasis diagnosis and 3 months after first SRE. Median survival in patients who did not experience SREs was 5 months. Among patients who received zoledronic acid before the first SRE, the median time to appearance of first SRE was significantly prolonged compared to control (7 months vs 4 months for control; P: 0.0005). CONCLUSIONS: To our knowledge, this retrospective analysis is the largest multicenter study to demonstrate that bone metastases from GC are not so rare, are commonly aggressive and result in relatively early onset of SREs in the majority of patients. Indeed, our large study, which included 90 patients treated with ZOL, showed, for the first time in literature, a significant extension of time to first SRE and increase in the median survival time after diagnosis of bone metastasis. Taken together, these data may support the beneficial effects of ZOL in GC patients.


Assuntos
Neoplasias Ósseas/epidemiologia , Neoplasias Ósseas/secundário , Neoplasias Gástricas/patologia , Adulto , Idoso , Conservadores da Densidade Óssea/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/mortalidade , Difosfonatos/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Avaliação de Resultados da Assistência ao Paciente , Vigilância da População , Prognóstico , Estudos Retrospectivos
6.
Oncology ; 64(4): 300-5, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12759524

RESUMO

OBJECTIVE: The aim of this study was to evaluate the activity and tolerability of docetaxel in patients with hormone-resistant prostate cancer previously exposed to chemotherapy. METHODS: We enrolled 27 patients with hormone-resistant prostatic cancer that had progressed during first-line chemotherapy. The primary end-point was palliative response defined as a 2-point reduction in the 6-point present pain intensity scale, and an improvement in Karnofsky performance status of one 10-point category. The treatment consisted of weekly docetaxel 25 mg/m(2) body surface area administered by means of a 1-hour intravenous infusion with corticosteroid premedication. RESULTS: The primary criterion of palliative response was met in 13 patients (48%) after eight treatment cycles; its median duration was 6 months (range 1-8). Mean global quality of life improved in 8 and 10 patients after respectively four and eight treatment cycles. After a median follow-up of 8 months, 21 patients had died: the median survival was 9+ months (range 2-18). Weekly docetaxel was very well tolerated: grade 3 neutropenia occurred in 1 patient and grade 3 anemia in 2. CONCLUSIONS: Weekly low-dose docetaxel is an effective and well-tolerated treatment for patients with hormone-resistant prostate cancer previously exposed to chemotherapy.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Paclitaxel/análogos & derivados , Paclitaxel/administração & dosagem , Neoplasias da Próstata/tratamento farmacológico , Taxoides , Idoso , Antineoplásicos Fitogênicos/efeitos adversos , Docetaxel , Esquema de Medicação , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Paclitaxel/efeitos adversos , Cuidados Paliativos/métodos , Neoplasias da Próstata/patologia , Qualidade de Vida , Resultado do Tratamento
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