RESUMO
Retrospective studies reported that preoperative oxaliplatin-based chemotherapy increased pathological response (PR) in patients resected for colorectal liver metastases (CRLM). This multicenter prospective randomized (1/1) phase II trial evaluated PR on resected CRLM after preoperative mFOLFOX6 (arm A) or FOLFIRI (arm B) + bevacizumab. The primary endpoint was the major pathological response rate (MPRR), defined as the percentage of patients presenting CRLMs with mean tumor regression grade (TRG) < 3. Secondary endpoints included safety, progression-free survival (PFS) and overall survival (OS). Out of 65 patients, 57 patients (28 and 29 in arm A/B) were resected for CRLM (one patient with lung metastases). Clinical and treatment characteristics were similar in both arms. One-month postoperative complications were 39.3%/31.0% in arm A/B (p = 0.585). MPRR and complete PR were 32.1%/20.7% (p = 0.379) and 14.3%/0.0% (p = 0.052) in arm A/B, respectively. PFS and OS were not different. Patients with PR among all CRLMs (max TRG ≤ 3; 43.8% of patients) had a lower risk of relapse (PFS: HR = 0.41, 95%CI = 0.204−0.840, p = 0.015) and a tendency towards better survival (OS: HR = 0.34, 95%CI = 0.104−1.114, p = 0.075). The homogeneity of PR was associated with improved PFS/OS. This trial fails to demonstrate a significant increase in MPRR in patients treated with mFOLFOX6-bevacizumab but confirms PR as an important prognostic factor.
Assuntos
Osso e Ossos/diagnóstico por imagem , Carcinoma de Células Acinares/diagnóstico por imagem , Carcinoma de Células Acinares/enzimologia , Lipase/sangue , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/enzimologia , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/enzimologia , Humanos , Masculino , Pessoa de Meia-Idade , CintilografiaRESUMO
OBJECTIVES: In mice, body weight is regulated by adipocyte-derived leptin. TNFalpha is a critical mediator of inflammation-induced cachexia in Crohn's disease (CD). The regulation of leptin by TNFalpha is poorly understood in CD. Pharmacological neutralization of TNFalpha with infliximab offers a unique opportunity to study TNFalpha-mediated regulation of leptin in CD patients. METHODS: We prospectively followed up CD patients treated with infliximab (n = 20). Body composition was assessed before and after treatment at 1 and 4 wk. Serum leptin, IL-6, soluble TNF receptor type II, and soluble intercellular antiadhesion molecule-1 levels were measured as well as cholesterol levels and free urinary cortisol. Because methylprednisolone (MP) increases leptin production in vivo, CD patients treated with MP (n = 9) were studied separately as a positive control group. RESULTS: Infliximab induced clinical remission and a significant decrease in C-reactive protein (P < 0.01) and IL-6 (P < 0.05) levels in all CD patients and increased body weight (P = 0.013) at 4 wk. Leptinemia was significantly increased after infliximab administration at 1 wk (P = 0.014) and 4 wk (P < 0.001). This increase in serum leptin occurred early at 1 wk, when no significant weight and fat mass changes could be observed and was associated with the down-regulation of TNFalpha-regulated mediators, soluble TNF receptor type II (P = 0.015), and soluble intercellular antiadhesion molecule-1 (P = 0.007). Moreover, infliximab increased cholesterol levels at 1 wk (P = 0.001). Twenty-four-hour cortisol secretion was not altered by infliximab. Leptinemia increased at 1 wk after MP administration (P = 0.028). CONCLUSION: Infliximab increases leptinemia in CD. This study suggests that TNFalpha exerts major inhibitory actions on leptin production in CD patients.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Doença de Crohn/sangue , Doença de Crohn/tratamento farmacológico , Leptina/sangue , Adulto , Biomarcadores/sangue , Índice de Massa Corporal , Feminino , Humanos , Infliximab , Interleucina-6/sangue , Masculino , Receptores para Leptina , Receptores Tipo II do Fator de Necrose Tumoral/sangue , Análise de Regressão , Fator de Necrose Tumoral alfa/fisiologia , Aumento de Peso/efeitos dos fármacosRESUMO
Small-cell carcinoma of the oesophagus (SCCO) is a rare and aggressive malignant tumour associated with a poor prognosis. Between 1994 and 2002, three patients with SCCO were treated in our institution, representing 1.96% (3 out of 153) of all oesophageal malignancies seen during this period. All of these patients had limited-stage SCCO at initial diagnosis and were treated by chemotherapy (cisplatin and etoposide) with concomitant radiotherapy. An initial complete response of the primary lesion was observed in all cases and a persistent complete remission in two of the cases. Chemo-radiotherapy should be considered as a valuable treatment alternative to surgery for limited-stage small-cell carcinoma of the oesophagus.