Tolerance of docetaxel: Is obesity a risk factor for toxicity? A pilot study.

248 Background: Few data are available in the literature regarding chemotherapy dosage adjustment in obese patients. Docetaxel is a lipophilic substance, highly bound to albumin; obesity might result in an accumulation and may lead to a higher rate of toxicity. The objective of this study was to assess the tolerance to docetaxel in obese and non obese patients, according to their body mass index (BMI). Methods: A retrospective study was performed. Patients were divided according to their BMI, considering a limit of 30 kg/m2. All patients received docetaxel (100 mg/m2) as a part of adjuvant chemotherapy for breast carcinoma. Toxicity of docetaxel such as neutropenia, hand-foot syndrome (HFS), mucositis, and neuropathy were assessed in both groups. The included patients received docetaxel alone or in association with trastuzumab or bevacizumab. Qualitative data analysis was performed using Fisher's exact test. Quantitative data were studied using the Student test. Results: Among the 49 patients, 18 (37%) presented with a BMI greater than 30 kg/m2. The median age was 53 years in the group BMI greater than 30 and 55 years in the group BMI less than 30 (p = 0.9383). The median value for albumin was 75 g/L (59-86 g/L) in the BMI greater than 30 and 71 g/L (56-79 g/L) in the BMI less than 30 (p = 0.122). Toxicity in both groups is shown in the table below. No neuropathy was observed. Conclusions: Obese patients (BMI > 30 kg/m2) presented with more toxicities (p = 0.013). Hypoalbuminemia did not represent a risk factor for toxicity in this study. Obesity is a risk factor for toxicity in patients treated with docetaxel. Dosage calculation according to body surface area is not suitable for these patients. Toxicity in the group BMI < 30 seems to demonstrate greater susceptibility to the molecule for these patients. Further studies will try to identify the different mechanisms of toxicity of docetaxel involved obese patients, including the interaction between docetaxel and fats. Measures have also to be taken to obtain a favorable effectiveness/toxicity balance in obese patients. [Table: see text]

Effects of epinephrine on branchial non-electrolyte permeability in rainbow trout

Using isolated heads perfused at constant pressure, at rates close to those occurring in vivo, the permeability of the gills of the trout Salmo gairdneri to a range of solutes was measured. Under epinephrine-free conditions, butanol and water showed similar high branchial permeability coefficients. Urea, inulin and dextrans (mol. wt 3000 and 20 000) were 7–12 times less permeant, and mannitol 60-70 times less permeant than water or butanol. Epinephrine, at 10(−6) M, greatly increased the permeability of the gills to the small hydrophilic molecules, water and urea, and to the lipophilic substance, butanol, but did not affect the penetration of the large hydrophilic solutes, mannitol, inulin and dextrans. In the presence of 10(−6) M propanolol, a beta-blocker, epinephrine had no effect on the permeation of any of the test substances except that the permeability to urea decreased somewhat. The results suggest that epinephrine increases the permeability of the membranes of the branchial cells but does not affect the permeation of substances that cross the gill walls by paracellular routes or via an intracellular ‘bulk-transport’ mechanism. Such an action would be expected to increase the branchial transfer of oxygen.

The chemical acceleration of the maturation process and its hormonal control in the male of the desert locust

The gregarious male of the desert locust shows a characteristic colour change during adult life; it is light brown and pink when immature, and bright yellow when mature. A mature, yellow male is able to accelerate the maturation process of young locusts by secreting a volatile substance which is produced in the epidermis and transmitted to the recipients by olfaction through the antennae and by contact over the body surface. The presence of this lipophilic substance is indicated by a vibration reaction, in which antennae, palpi and hind femora take part (Loher 1959). The volatile material can be extracted and preserved in oil and fat solvents. Extirpation and implantation of the corpora allata have demonstrated that in the male these endocrine glands are in control of sexual maturation and some associated processes, such as the production of the epidermal secretory substance, the colour change, the development of the accessory glands and the acceleration of maturation which results from wounding. The possibilities of combined action between the corpora allata and the epidermal secretory substance are discussed.