Pemetrexed-induced eyelid edema in lung cancer.

Pemetrexed is a novel, multitargeted antifolate approved for the treatment of malignant pleural mesothelioma and non-small cell lung cancer. Although pemetrexed is a safe drug, some adverse effects such as myelosupression and cutaneous reactions are observed. Pemetrexed-induced eyelid edema is a rare side effect of pemetrexed treatment, and until this moment few cases were reported in the medical literature. We reported a new case of pemetrexed-induced eyelid edema in a patient with adenocarcinoma of the lung with brain metastases.

Quality of life in patients with advanced non-small-cell lung cancer given maintenance treatment with pemetrexed versus placebo (H3E-MC-JMEN): results from a randomised, double-blind, phase 3 study.

BACKGROUND: Pemetrexed maintenance therapy significantly improved overall survival and progression-free survival compared with placebo, and had a good safety profile in a phase 3 placebo-controlled study in patients with advanced non-small-cell lung cancer (NSCLC). Results for quality of life, symptom palliation, and tolerability are presented here. METHODS: After four cycles of platinum-based induction therapy, 663 patients with stage IIIB or stage IV NSCLC and Eastern Cooperative Oncology Group performance status of 0 or 1 were randomly assigned (in a 2:1 ratio) from March 15, 2005, to July 20, 2007, using the Pocock and Simon minimisation method to receive pemetrexed (500 mg/m(2) every 21 days; n=441) or placebo (n=222) plus best supportive care until disease progression. The primary efficacy data have been reported previously. Patients completed the Lung Cancer Symptom Scale (LCSS) at baseline, after each cycle, and post-discontinuation. Worsening of symptoms was defined as an increase of 15 mm or more from baseline on a 100 mm scale for each LCSS item. The primary outcome for these quality-of-life analyses was time to worsening of symptoms, analysed for all randomised patients. This study is registered with ClinicalTrials.gov, number NCT00102804. FINDINGS: Baseline characteristics, including LCSS scores, were well balanced between groups. Baseline LCSS scores were low, indicating low symptom burden for patients without disease progression after completion of first-line treatment. Longer time to worsening was recorded for pain (hazard ratio [HR] 0·76, 95% CI 0·59-0·99; p=0·041) and haemoptysis (HR 0·58, 95% CI 0·34-0·97; p=0·038) with pemetrexed than with placebo; no other significant differences in analyses of time to worsening were noted. Additional longitudinal analyses showed a greater increase in loss of appetite in the pemetrexed group than in the placebo group (4·3 mm vs 0·2 mm; p=0·028). Rates of resource use were statistically higher for pemetrexed than for placebo: admissions to hospital for drug-related adverse events (19 [4%] vs none; p=0·001), transfusions (42 [10%] vs seven [3%]; p=0·003), and erythropoiesis-stimulating agents (26 [6%] vs four [2%]; p=0·017). INTERPRETATION: Quality of life during maintenance therapy with pemetrexed is similar to placebo, except for a small increase in loss of appetite, and significantly delayed worsening of pain and haemoptysis. In view of the improvements in overall and progression-free survival noted with pemetrexed maintenance therapy, such treatment is an option for patients with advanced non-squamous NSCLC who have not progressed after platinum-based induction therapy. FUNDING: Eli Lilly.

Efeito da glutamina em matrizes suínas lactantes

Objetivou-se, avaliar a influência da suplementação de L-Glutamina mais L-Glutamato nos principais componentes do leite (gordura, proteína, lactose, sólidos totais e Contagem de Células Somáticas), durante os 21 dias de lactação. Utilizou-se 30 matrizes suínas híbridas de linhagem Dalland divididas em dois tratamentos: Controle e Aminogut que receberam 1,5% de Aminogut (L-Gln + L-Glu) na ração. As fêmeas foram alojadas no galpão maternidade, em gaiolas individuais. A suplementação iniciou-se uma semana antes do parto. Nos dias 1 (dia do parto), 7 (uma semana pós-parto) e 21 (dia do desmame) foram coletadas amostras de colostro e leite com volume médio de 30 mL, coletado nas tetas peitorais. As amostras foram refrigeradas e analisadas no laboratório de leite PROGENE da UFRPE, para determinação dos valores percentuais de proteína, gordura, sólidos totais e lactose e a contagem de células somáticas (CCS). Utilizou-se delineamento inteiramente casualizado com dois tratamentos (Controle e Aminogut), todas as variáveis estudadas foram analisadas no Pacote Estatístico Statistical Analysis System – SAS, versão 8, individualmente e de suas interações. A glutamina influenciou (P<0,01) o teor de gordura, de sólidos totais e de CCS do colostro e leite de porcas. Não houve interação entre as variáveis.

Comedolytic effect and reduced skin irritation of a new formulation of all-trans retinoic acid-loaded solid lipid nanoparticles for topical treatment of acne.

Novel drug delivery systems, such as solid lipid nanoparticles (SLN), have been proposed to reduce retinoic acid (RA)-induced skin irritation. However, one question still remains: could it be accomplished without reducing efficacy? To evaluate this question the comedolytic effects and epidermal thickening of RA-loaded SLN were compared to the conventional RA formulations (gel or cream), as well as the potential of these formulations to induce skin irritation. The comedolytic effects and epidermal thickening of these formulations, both containing RA at 0.01 or 0.05%, were investigated in a rhino mouse model, while the studies of RA-induced skin irritation were evaluated through rabbit skin irritation tests and in the rhino mouse model. RA-loaded SLN, as compared to the placebo, produced a comedolytic effect with a significant reduction of the utricle diameter, which proved to be similar to that observed for marketed gels or creams regardless of the RA concentration. RA formulations (SLN or marketed cream) also induced an epidermal proliferation leading to a thickened epidermis in treated animals. In both animals studied (rhino mice and rabbits), the RA-loaded SLN, when compared to conventional formulations, promoted a significant reduction in RA-induced skin irritation (erythema and scaling). Then, RA-loaded SLN represents an interesting alternative to reduce RA-induced skin irritation without reducing efficacy, and constitutes an innovative approach for the topical treatment of acne with RA.

Antinociceptive effects of citronellal in formalin-, capsaicin-, and glutamate-induced orofacial nociception in rodents and its action on nerve excitability.

AIMS: To evaluate the antinociceptive effects of citronellal (CTL) on formalin-, capsaicin-, and glutamate-induced orofacial nociception in mice and to investigate whether such effects might involve a change in neural excitability. METHODS: Male mice were pretreated with CTL (50, 100, and 200 mg/kg, ip), morphine (5 mg/kg, ip), or vehicle (distilled water plus one drop of Tween 80 0.2%) before formalin (20 microL, 2%), capsaicin (20 microL, 2.5 microg) or glutamate (40 microL, 25 microM) injection into the right vibrissa. Sciatic nerve recordings were made using the single sucrose gap technique in rats. The data obtained were analyzed by ANOVA followed by Dunnett's test for the behavioral analyses and by the Student t test for CAP evaluation. RESULTS: Pretreatment with CTL was effective in reducing nociceptive face-rubbing behavior in both phases of the formalin test, which was also naloxone-sensitive. CTL produced significantly antinociceptive effect at all doses in the capsaicin- and glutamate- tests. Rota-rod testing indicated that such results were unlikely to be provoked by motor abnormality. Recordings using the single sucrose gap technique revealed that CTL (10 mM) could reduce the excitability of the isolated sciatic nerve through a diminution of the compound action potential amplitude by about 42.4% from control recordings. CONCLUSION: These results suggest that CTL might represent an important tool for management and/or treatment of orofacial pain.

Management of platinum-resistant ovarian cancer with the combination of pemetrexed and gemcitabine.

INTRODUCTION: Platinum resistant ovarian cancer is a current challenge in Oncology. Current approved therapies offer no more of a 20% of response. New therapeutic options are urgently needed. PATIENTS AND METHODS: Patients were treated with the combination of Pemetrexed 500 mg/m(2) d1 and Gemcitabine 1000 mg/m(2) d1,8 in a 21 days basis. RESULTS: 10 platinum-resistant ovarian cancer patients were treated under compassionate use. Mean previous chemotherapy lines were 3.3. Mean administered cycles were 4. Mean CA 125 decrease was on average of 47%, with one patient experiencing a 95% decrease in her CA 125 level. 1 patient had a complete clinical remission, and 2, had partial radiological responses. Mean Progression free survival was 16.5 weeks, and Overall Survival was 21.2 weeks. Treatment was well tolerated. CONCLUSIONS: Deemd to the observed activity, the combination of Pemetrexed and Gemcitabine deserves deeper investigation in platinum-resistant ovarian cancer patients.