RESUMO
BACKGROUND: Clinical trials in metastatic colorectal cancer (mCRC) are usually conducted irrespective of sex. Sex-associated differences relating to safety and efficacy in the treatment of mCRC, however, are gaining interest. METHODS: PanaMa investigated the efficacy of panitumumab (Pmab) plus fluorouracil and folinic acid (FU/FA) versus FU/FA alone after induction therapy with six cycles of FU/FA and oxaliplatin plus Pmab in patients with RAS wild-type mCRC. In this post hoc analysis, the study population was stratified for sex. Evaluated efficacy endpoints during maintenance treatment were progression-free survival (PFS, primary endpoint of the trial), overall survival (OS) and objective response rate during maintenance therapy. Safety endpoints were rates of any grade and grade 3/4 adverse events during maintenance therapy. RESULTS: In total, 165 male and 83 female patients were randomized and treated. Male and female patients showed numerically better objective response rates with Pmab, without reaching statistical significance. Male patients derived a significant benefit from the addition of Pmab to maintenance treatment with regard to PFS [hazard ratio (HR) 0.63; 95% confidence interval (CI) 0.45-0.88; P = 0.006] that was not observed in female patients (HR 0.85; 95% CI 0.53-1.35; P = 0.491). The better PFS for male patients treated with Pmab did not translate into improved OS (HR 0.85; 95% CI 0.55-1.30; P = 0.452). Female patients showed numerically improved OS when treated with Pmab. There was no difference in the total of grade ≥3 adverse events during maintenance regarding sex (P = 0.791). Female patients, however, had a higher rate of any grade nausea, diarrhea and stomatitis. CONCLUSIONS: In the PanaMa trial, the addition of Pmab to maintenance treatment of RAS wild-type mCRC with FU/FA improved the outcome in terms of the primary endpoint (PFS) particularly in male patients. Female patients did not show the same benefit while experiencing higher rates of adverse events. Our results support the development of sex-specific protocols.
Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Humanos , Masculino , Feminino , Panitumumabe/farmacologia , Panitumumabe/uso terapêutico , Leucovorina/efeitos adversos , Neoplasias Colorretais/patologia , Resultado do Tratamento , Fluoruracila/efeitos adversos , Neoplasias do Colo/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
Dietary protein adjustments can reduce environmental impact and economic losses in production systems. However, we lack information regarding nitrogen (N) metabolism and protein requirements for maintenance of crossbred animals such as Red Norte breed, precluding a precise dietary management. The objective was to evaluate the effect of increasing dietary CP levels (9%, 11%, 13%, 15% and 17%) on intake, digestibility and N balance, as well as to estimate the metabolizable protein requirements for maintenance (MPm) of growing Red Norte bulls. Thirty five animals averaging 280 ± 4.0 kg BW were fed during 45 days in a 60 : 40 forage : concentrate ratio diet in which the last 5 days were used for the digestibility trial. Intakes of CP and non-fibrous carbohydrates (NFCs) and feed efficiency linearly increased (P < 0.05) as CP levels increased, while DM, NDF, nitrogen efficiency use and ether extract were not influenced by CP levels (P > 0.05). Digestibilities of DM, organic matter, ether extract, NFC and CP as well as metabolizable energy intake linearly increased (P < 0.05), and true digestibility of CP was not affected (P > 0.05) by treatments. Urinary N and retained N linearly increased (P < 0.05) with the increase in dietary N. The MPm were estimated as 4.46 g/BW0.75 and the efficiency of use of MPm was 0.673. In conclusion, obtained MPm requirements of growing Red Norte bulls are greater than the values reported in literature for Zebu cattle and dietary CP levels of 15% and 17% exhibited great responses for growing Red Norte cattle. However, a cost-benefit evaluation should be done before its use.