RESUMO
PURPOSE: This randomized phase II trial evaluated whether the combination of cisplatin and paclitaxel (PC) plus all-trans retinoic acid (ATRA) increases response rate (RR) and progression-free survival (PFS) in patients with advanced non-small-cell lung cancer (NSCLC) with an acceptable toxicity profile and its association with the expression of retinoic acid receptor beta 2 (RAR-beta2) as a response biomarker. PATIENTS AND METHODS: Patients with stages IIIB with pleural effusion and IV NSCLC were included to receive PC, and randomly assigned to receive ATRA 20 mg/m(2)/d (RA/PC) or placebo (P/PC) 1 week before treatment until two cycles were completed. RAR-beta2 expression was analyzed in tumor and adjacent lung tissue. RESULTS: One hundred seven patients were included, 55 in the P/PC group and 52 in the RA/PC group. RR for RA/PC was 55.8% (95% CI, 46.6% to 64.9%) and for P/PC, 25.4% (95% CI, 21.3 to 29.5%; P = .001). The RA/PC group had a longer median PFS (8.9 v 6.0 months; P = .008). Multivariate analysis of PFS showed significant differences for the RA/PC group (hazard ratio, 0.62; 95% CI, 0.4 to 0.95). No significant differences in toxicity grade 3/4 were found between groups, except for hypertriglyceridemia (10% v 0%) in RA/PC (P = .05). Immunohistochemistry and reverse-transcriptase polymerase chain reaction assays showed expression of RAR-beta2 in normal tissues of all tumor samples, but only 10% of samples in the tumor tissue. CONCLUSION: Adding ATRA to chemotherapy could increase RR and PFS in patients with advanced NSCLC with an acceptable toxicity profile. A phase III clinical trial is warranted to confirm these findings.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Cisplatino/administração & dosagem , Método Duplo-Cego , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Receptores do Ácido Retinoico/análise , Tretinoína/administração & dosagemRESUMO
BACKGROUND: The presence and detection of multifocal and multicentric disease significantly increases the risk of recurrence and changes the best therapeutic approach in patients with breast cancer. Mammography has low sensitivity to detect multiple malignant foci in patients with dense breast parenchyma. We prospectively evaluated Magnetic Resonance Imaging (MRI) as part of preoperative assessment. MATERIAL AND METHODS: Women with clinical and radiological suspicion of breast cancer and dense breast parenchyma (> 75% dense tissue) were included. All patients underwent mammography, ultrasonogram and MRI prior to surgery. Surgical specimens were used for the detection of multifocal and multicentric disease. Patients who required neoadjuvant chemotherapy or radiotherapy were excluded. RESULTS: Nineteen patients were evaluated. Histological diagnosis was confirmed in 14 patients, multifocal and multicentric disease was found in five and two patients, respectively. Sensitivity and accuracy to detect multiple malignant foci were 42 and 64%, respectively, for mammography plus ultrasound and 100 and 92% for MRI (p<0.05). CONCLUSIONS: MRI is more sensible and has a better accuracy than mammography plus ultrasound to detect both multicentric and multifocal breast cancer in women with dense breast parenchyma. MRI can improve preoperative assessment of breast cancer in this group of patients.
Assuntos
Neoplasias da Mama/patologia , Mama/patologia , Carcinoma/patologia , Imageamento por Ressonância Magnética , Neoplasias Primárias Múltiplas/patologia , Cuidados Pré-Operatórios/métodos , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Carcinoma/diagnóstico por imagem , Carcinoma/cirurgia , Meios de Contraste , Feminino , Gadolínio DTPA , Humanos , Imageamento Tridimensional , Metástase Linfática , Mastectomia , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/cirurgia , Valor Preditivo dos Testes , Estudos Prospectivos , Radiografia , Sensibilidade e Especificidade , UltrassonografiaRESUMO
Hepatocellular carcinoma is the fifth most common malignant neoplasm worldwide. Most patients are not candidates to surgical treatment. The prognosis of this neoplasm is poor, with an overall survival rate of 8 weeks in unresectable tumors. Estrogen receptors have been found in up to 33% of this tumors, reason why treatment with tamoxifen or progesterone compounds have been tried to diminish this neoplasm's progression but its use remains controversial. In our institution, thirteen patients were treated with tamoxifen (20- 40 mg/day) and 26 received supportive measures only. The clinical and tumoral characteristics were similar in both groups. Survival in the Tamoxifen group was of 5.5 +/- 1.7 months while in the supportive measures group was of 2.1 +/- 0.5 months (p = 0.018). Other factors related to an increased survival were: female gender and the Okuda score; age, TNM and alphaFP were not related to survival. The multivariate analysis showed that treatment with tamoxifen duplicates survival independently of the tumoral stage and functional hepatic reserve. It seems that the benefit of treatment with tamoxifen is limited and is not associated to the presence of estrogen receptors. In our study a 69 year-old man with diagnosis of non-resectable hepatocellular carcinoma and negative estrogen receptors, was treated with tamoxifen with a partial response and an overall survival of 4 years until November 2005. Despite some case reports that have shown tumoral regression, while other studies do not report any survival benefits. It is important to identify patients that would benefit from treatment with tamoxifen.