Effects of subcutaneous methadone, morphine, buprenorphine or saline on thermal and pressure thresholds in cats.

This study compared pressure and thermal thresholds after administration of three opioids in eight cats. Pressure stimulation was performed via a bracelet taped around the forearm. Three ball-bearings were advanced against the forearm by inflation of a modified blood pressure bladder. Pressure in the cuff was recorded at the end point (leg shake and head turn). Thermal threshold was tested as previously reported using a heated probe held against the thorax [Dixon et al. (2002) Research in Veterinary Science, 72, 205]. After baseline recordings, each cat received subcutaneous methadone 0.2 mg/kg, morphine 0.2 mg/kg, buprenorphine 0.02 mg/kg or saline 0.3 mL in a four period cross-over study. Measurements were made at 15, 30, 45 min and 1, 2, 3, 4, 8, 12 and 24 h after the injection. Data were analysed by anova (P<0.05). There were no significant changes in thresholds after saline. Thermal threshold increased at 45 min after buprenorphine (maximum 2.8+/-3 degrees C), 1-3 h after methadone (maximum 3.4+/-1.9 degrees C) and 45 min to 1 h (maximum 3.4+/-2 degrees C) after morphine. Pressure threshold increased 30-45 min (maximum 238+/-206 mmHg) after buprenorphine, 45-60 min after methadone (maximum 255+/-232 mmHg) and 45-60 min and 3-6 h (maximum 255+/-232 mmHg) after morphine. Morphine provided the best analgesia, and methadone appears a promising alternative. Buprenorphines limited effect was probably related to the subcutaneous route of administration. Previously, buprenorphine has produced much greater effects when given by other routes.

Gemcitabine with either paclitaxel or vinorelbine vs paclitaxel or gemcitabine alone for elderly or unfit advanced non-small-cell lung cancer patients.

The aim of this study was to assess whether a combination of gemcitabine (GEM) with either paclitaxel (PTX) or vinorelbine (VNR) could be more effective than GEM or PTX alone in elderly or unfit advanced non-small-cell lung cancer (NSCLC) patients. A total of 264 NSCLC patients aged >70 years with ECOG performance status (PS)< or =2, or younger with PS=2, were randomly treated with: GEM 1200 mg m(-2) on days 1, 8 and 15 every 28 days; PTX 100 mg m(-2) on days 1, 8 and 15 every 28 days; GEM 1000 mg m(-2) plus PTX 80 mg m(-2) (GT) on days 1 and 8 every 21 days; GEM 1000 mg m(-2) plus VNR 25 mg m(-2) (GV) on days 1 and 8 every 21 days. In all arms, an intra-patients dose escalation was applied over the first three courses, provided that no toxicity of WHO grade > or =2 had previously occurred. At present time, 217 (82%) patients had died. The median (months) and 1-year survival probability were 5.1 and 29% for GEM, 6.4 and 25% for PTX, 9.2 and 44% for GT, and 9.7 and 32% for GV. Multivariate analysis showed that PS< or =1 (hazard ratio (HR)=0.67; 95% CI 0.51-0.90), and doublet treatments (HR=0.76; 95% CI 0.59-0.99) were significantly associated with longer survival. Doublets produced no more toxicity than single agents. GT should be considered a reference regimen for elderly NSCLC patients with PS< or =1.

Cisplatin, epirubicin, and vindesine with or without lonidamine in the treatment of inoperable nonsmall cell lung carcinoma: a multicenter randomized clinical trial.

BACKGROUND: Lonidamine (LND) is an indazol-carboxylic acid derivative that selectively inhibits the energy metabolism of neoplastic cells, and increases the permeability of cell membranes. In vitro studies have demonstrated that LND can potentiate the oncolytic activity of cytotoxic drugs and is able to reverse the acquired multidrug resistance of neoplastic cells. Some clinical trials have suggested a synergism of LND with alkylating agents, cisplatin, and anthracyclines in various solid tumors. METHODS: From June 1990 to June 1993, 158 previously untreated patients with Stage IIIB and IV nonsmall cell lung cancer (NSCLC) were enrolled into a multicentric randomized trial to evaluate the addition of LND to a cisplatin-epirubicin-vindesine regimen. Eighty patients in the control arm (A) received cisplatin, 60 mg/m2 intravenously (i.v.); epirubicin, 60 mg/m2 i.v.; and vindesine, 3 mg/m2 i.v. (PEV), on Day 1 every 4 weeks, whereas 78 patients in the experimental arm (B) received the same regimen with the addition of LND from 75 mg orally three times on Day 1 to 150 mg orally three times on Day 7+ until tumor progression occurred. RESULTS: The experimental treatment achieved a significantly higher proportion of major responses in comparison with the control regimen (43% vs. 24%; P=0.02). The addition of LND apparently potentiated the activity of this cytotoxic treatment, particularly in patients with metastatic disease (overall response rate, 39% vs. 17%). The median time to progression (5 vs. 8 months; P=0.0007) and the median survival time (7.6 vs. 11 months; P=0.0013) were also statistically improved in Arm B. The acute toxicity of the 2 treatments was low: only 6% of patients in Arm A and 4% of patients in Arm B had to withdraw from treatment due to Grade 4 World Health Organization toxicity. The main additional side effects related to the administration of LND were epigastralgia, myalgia, asthenia, and orchialgia. However, these symptoms were mild and controlled by the concomitant administration of low doses of steroids. CONCLUSIONS: The mild acute toxicity of the PEV regimen and the acceptable and nonoverlapping additional side effects of LND render our experimental therapy worthy of consideration for the management of NSCLC patients with poor performance status or low tolerance to more aggressive therapeutic approaches.

Tratamento de longa duraçäo com "Duovent" em pacientes idosas portadores de doença pulmonar obstrutiva crônica / Long term treatment using Duovent in elderly patients with chronic obstructive pulmonary diseases

Doze pacientes, com idade de 60 anos e portadores de doença pulmonar obstrutiva crônica, foram tratados durante 12 semanas com Duovent (fenoterol + brometo de ipratrópio). As avaliaçöes clínicas e índice de obstruçäo brônquica (VEF1, CV, VR, CEVA) foram realizados cada 14 dias. A melhora dos sintomas correspondeu a uma melhora significante dos parâmetros funcionais. Näo se observou efeito cardiovascular negativo, efeitos colaterais significativos ou tolerância após a administraçäo da droga

Long-term treatment with 'Duovent' in elderly patients affected by chronic obstructive lung disease.

Twelve patients, aged over 60 years and suffering from chronic obstructive lung disease, were treated for 12 weeks with Duovent (fenoterol + ipratropium bromide). The clinical check-ups and indices of bronchial obstruction (FEV1, VC, RV, sGaw) were performed every 14 days. Improvement in symptoms corresponded to a significant improvement in the functional parameters. No negative cardiovascular effects, significant side-effects, or tolerance were seen after drug administration.