Detailed analysis of a randomized phase III trial: can the tolerability of capecitabine plus docetaxel be improved without compromising its survival advantage?

BACKGROUND: In a phase III trial, 3-weekly capecitabine (1250 mg/m(2) twice daily days 1-14) plus docetaxel (75 mg/m(2) day 1) demonstrated significantly superior overall survival to 3-weekly docetaxel (100 mg/m(2) day 1). We report a retrospective analysis of the impact of capecitabine/docetaxel dose reduction on safety and efficacy. PATIENTS AND METHODS: Safety and efficacy data were analyzed retrospectively according to the actual doses of capecitabine and docetaxel administered. RESULTS: More patients receiving capecitabine/docetaxel (65%) had dose reductions for adverse events than docetaxel alone (35%). In most patients requiring dose reduction with the combination (80%), capecitabine and docetaxel were simultaneously reduced to 950 mg/m(2) and 55 mg/m(2), respectively. Subsequently, there were fewer cycles (17%) with grade 3/4 adverse events than with the full doses (34%). Time to progression and overall survival appeared to be similar in patients starting the second cycle with reduced doses of capecitabine/docetaxel and those who continued to receive full doses of capecitabine/docetaxel for at least the first four cycles. CONCLUSIONS: Capecitabine/docetaxel dosing flexibility allows management of side-effects without compromising efficacy. This retrospective analysis, as well as multiple phase II studies of taxanes with reduced-dose capecitabine, shows that reducing the starting dose of capecitabine with docetaxel is a reasonable strategy for the treatment of patients with metastatic breast cancer. In addition, reducing the dose of both agents may be appropriate.

Body mass index, waist circumference and waist-hip ratio and serum levels of IGF-I and IGFBP-3 in European women.

OBJECTIVE: To examine the relationship between body mass index (BMI) and waist-hip ratio (WHR) with serum levels of insulin-like growth factor-I (IGF-I), and its binding protein (IGFBP)-3. DESIGN: Cross-sectional study on 2139 women participating in a case-control study on breast cancer and endogenous hormones. Data on lifestyle and reproductive factors were collected by means of questionnaires. Body height, weight, waist and hip circumferences were measured. Serum levels of IGF-I and insulin-like binding protein (IGFBP)-3 were measured by enzyme-linked immunosorbent assays. Adjusted mean levels of IGF-I and IGFBP-3 across quintiles of BMI, waist circumference, and WHR were calculated by linear regression. Results were adjusted for potential confounders associated with IGF-I and IGFBP-3. RESULTS: Adjusted mean serum IGF-I values were lower in women with BMI<22.5 kg/m(2) or BMI>29.2 kg/m(2) compared to women with BMI within this range (P(heterogeneity)<0.0001, P(trend)=0.35). Insulin-like growth factor-I was not related to WHR after adjustment for BMI. IGF-binding protein-3 was linearly positively related to waist and WHR after mutual adjustment. The molar ratio IGF-I/IGFBP-3 had a non-linear relation with BMI and a linear inverse relationship with WHR (P (trend)=0.005). CONCLUSIONS: Our data confirm the nonlinear relationship of circulating IGF-I to total adiposity in women. Serum IGFBP-3 was positively related to central adiposity. These suggest that bioavailable IGF-I levels could be lower in obese compared to non-obese women and inversely related to central adiposity.

[In vitro control of Sclerotinia sclerotiorum and Gaeumannomyces graminis by bacteria of the fluorescent Pseudomonas group]. / Control in vitro de Sclerotinia sclerotiorum y Gaeumannomyces graminis por bacterias del grupo Pseudomonas fluorescentes.

Thirty six fluorescent Pseudomonas isolates were obtained from the rhizosphere of sunflower plants. By antibiosis tests, the six more efficient strains in Sclerotinia sclerotiorum growth inhibition, were selected. Simultaneously, twenty three fluorescent Pseudomonas isolates were recuperated from the rhizosphere of wheat plants and the five most efficient strains in growth inhibition of the fungi Gaeumannomyces graminis were selected. The strains selected from the rhizosphere of sunflower plants had no antagonistic effect on G. graminis and the bacteria isolated from the wheat rhizosphere showed no fungistatic activity on S. sclerotiorum. These results suggest the existence of a certain degree of plant bacteria pathogenic specificity. Among the selected bacteria, the strain FF5 of P. fluorescens originated the major inhibiting halo in vitro against S. sclerotiorum (Figure 1). In liquid culture medium this bacterium produces an antifungal substance that promotes lysis of fungi mycelium (Figure 2) and inhibition of ascospore germination and is not inhibited by the presence of Fe+3 in the culture medium (Table 1). Its synthesis is not associated with the production of fluorescein. Its action is not enzymatic because it is a substance of low molecular weight (< 2000), resistant to autoclave sterilization and photo-stable. The amount of NH4+ and the high pH values produced by the FF5 strain in the liquid culture medium (Table 2) are not responsible for the antifungalal action.

Control in vitro de Sclerotinia sclerotiorum y Gaeumannomyces graminis por bacterias del grupo Pseudomonas fluorescentes / [In vitro control of Sclerotinia sclerotiorum and Gaeumannomyces graminis by bacteria of the fluorescent Pseudomonas group]

Thirty six fluorescent Pseudomonas isolates were obtained from the rhizosphere of sunflower plants. By antibiosis tests, the six more efficient strains in Sclerotinia sclerotiorum growth inhibition, were selected. Simultaneously, twenty three fluorescent Pseudomonas isolates were recuperated from the rhizosphere of wheat plants and the five most efficient strains in growth inhibition of the fungi Gaeumannomyces graminis were selected. The strains selected from the rhizosphere of sunflower plants had no antagonistic effect on G. graminis and the bacteria isolated from the wheat rhizosphere showed no fungistatic activity on S. sclerotiorum. These results suggest the existence of a certain degree of plant bacteria pathogenic specificity. Among the selected bacteria, the strain FF5 of P. fluorescens originated the major inhibiting halo in vitro against S. sclerotiorum (Figure 1). In liquid culture medium this bacterium produces an antifungal substance that promotes lysis of fungi mycelium (Figure 2) and inhibition of ascospore germination and is not inhibited by the presence of Fe+3 in the culture medium (Table 1). Its synthesis is not associated with the production of fluorescein. Its action is not enzymatic because it is a substance of low molecular weight (< 2000), resistant to autoclave sterilization and photo-stable. The amount of NH4+ and the high pH values produced by the FF5 strain in the liquid culture medium (Table 2) are not responsible for the antifungalal action.

Control in vitro de Sclerotinia sclerotiorum y Gaeumannomyces graminis por bacterias del grupo Pseudomonas fluorescentes. / [In vitro control of Sclerotinia sclerotiorum and Gaeumannomyces graminis by bacteria of the fluorescent Pseudomonas group]

Thirty six fluorescent Pseudomonas isolates were obtained from the rhizosphere of sunflower plants. By antibiosis tests, the six more efficient strains in Sclerotinia sclerotiorum growth inhibition, were selected. Simultaneously, twenty three fluorescent Pseudomonas isolates were recuperated from the rhizosphere of wheat plants and the five most efficient strains in growth inhibition of the fungi Gaeumannomyces graminis were selected. The strains selected from the rhizosphere of sunflower plants had no antagonistic effect on G. graminis and the bacteria isolated from the wheat rhizosphere showed no fungistatic activity on S. sclerotiorum. These results suggest the existence of a certain degree of plant bacteria pathogenic specificity. Among the selected bacteria, the strain FF5 of P. fluorescens originated the major inhibiting halo in vitro against S. sclerotiorum (Figure 1). In liquid culture medium this bacterium produces an antifungal substance that promotes lysis of fungi mycelium (Figure 2) and inhibition of ascospore germination and is not inhibited by the presence of Fe+3 in the culture medium (Table 1). Its synthesis is not associated with the production of fluorescein. Its action is not enzymatic because it is a substance of low molecular weight (< 2000), resistant to autoclave sterilization and photo-stable. The amount of NH4+ and the high pH values produced by the FF5 strain in the liquid culture medium (Table 2) are not responsible for the antifungalal action.

Estado convulsivo: consideraciones acerca de su clasificación y terapéutica / Convulsive state: considerations about their classification and therapeutic

Se presentan algunas consideraciones sobre el estadoconvulsivo mas conocido por estaco epileptico, su clasificación y tratamiento. Se muestran resultados deuna investigación de los ultimos 6 años (hasta abrilde 1992) en la unidad de cuidados intensivos de nuestro hospital que incluyó a 42 pacientes los cuales presentaron 52 episodios, la epilepsia fue la etiología principal y el factor fundamental lo constituyó el abandono del tratamiento el tipo de convulsión masfrecuente fue la tonico-clonica generalizada y el tratamiento. El tipo de convulsión mas frecuente fue la tónico-clónica generalizada y el tratamiento se basó en el uso de diazepan, fenitoina y fenobarbital