Phase I/II study of atrasentan, an endothelin A receptor antagonist, in combination with paclitaxel and carboplatin as first-line therapy in advanced non-small cell lung cancer.

PURPOSE: Endothelins and their cell membrane receptors (ET(A)R and ET(B)R) are implicated in neoplastic pathogenesis. atrasentan, a potent, selective ET(A)R antagonist, has a direct effect on tumor proliferation, apoptosis, and angiogenesis. This study was designed to assess the influence of atrasentan on paclitaxel pharmacokinetics and to determine the safety and efficacy of atrasentan in combination with paclitaxel-carboplatin. EXPERIMENTAL DESIGN: Chemonaive patients with stage IIIB (malignant pleural effusion) and IV non-small cell lung cancer were enrolled. Toxicity and response were determined using the National Cancer Institute Common Toxicity Criteria version 2.0 and Response Evaluation Criteria in Solid Tumors criteria, respectively. Treatment consisted of paclitaxel (225 mg/m(2)) and carboplatin (area under the curve, 6) administered on day 1 every 3 weeks. A fixed 10 mg daily oral dose ofAtrasentan was administered continuously, starting on day 4 of cycle 1. Paclitaxel clearance was calculated during the first two cycles (pre- and post-atrasentan) in the first 10 patients. RESULTS: All 44 patients were evaluable for survival, toxicity, and response. No significant change in mean paclitaxel clearance was detected (mean +/- SD, 21.2 +/- 4.5 L/h versus 21.3 +/- 4.9 L/h) for pre- and post-atrasentan values, respectively (P = 0.434). Grade 3/4 toxicities > or = 10% were lymphopenia (22.7%), neutropenia (20.5%), dyspnea (11.4%), and hyperglycemia (11.4%). Response rate was 18.2%, with progression-free survival of 4.2 months, median survival of 10.6 months, and 1-year survival of 43%. CONCLUSION: Atrasentan plus paclitaxel-carboplatin was safe and well tolerated, with no apparent paclitaxel-atrasentan pharmacokinetic interaction. Efficacy and survival in advanced non-small cell lung cancer were comparable with studies of chemotherapy alone.     

Hypolipedaemic activity of picroliv in albino rats

The hypolipidaemic action of picroliv, a standarized preparaton from Picrorhiza kurrooa, has been studied in normal as well as in triton- and cholesterol-fed rats. Serum lipids were found to be lowered by picroliv (25 mg/kg b.w.) in triton WR-1339-induced hyperlipaemia. Chronic feeding of this drug (6 mg/kg b.w.) in normal rats and in animals simultaneously treated with cholesterol (25 mg/kg b.w.) for 30 days caused lowering in the lipid and protein levels constituting β-lipoproteins followed by an increase in high density lipoprotein cholesterol in experimental animals. Picroliv alters lipolytic activities in plasma, liver, heart an adipose tissues and stimulated receptor mediated catabolism of low density lipoprotein. The lipid lowering action of the natural product is mediated through inhibition of cholesterol biosynthesis in liver, increased faecal bile acid excretion and enhanced plasma lecithin: cholesterol acyltransferase activity.     

Subclinical group A streptococcal throat infection in school children.

Seven hundred and forty nine apparently healthy school children aged 5-15 years were investigated for throat infection with Group A streptococci (GAS) during December 1990 to May 1991. The prevalence of beta hemolytic streptococci (BHS) was 18.8%; most organisms belonged to Group A streptococci (13.7%). The prevalence of BHS in throat was significantly higher (p < .001) in girls as compared to boys. Immune response to extracellular antigens was studied in 53 children who had GAS strain in their throat, 54.7% had elevated titers of antistreptolysin O or antideoxyribonuclease B or both indicating subclinical infection with GAS. Thus it is recommended that serological examinations should be done along with throat culture to identify subclinical Group A streptococcal throat infection.     

Molecular adsorbent recirculating system: albumin dialysis-based extracorporeal liver assist device

Extracorporeal liver assist devices have been used for more than five decades to support patients with liver failure. Numerous modifications have been made to both biological as well as mechanical liver assist devices. Possibly, an ideal liver assist device would be one that would perform optimal detoxification and synthetic functions of the liver, be simple to set up and yet be cost-effective. An albumin dialysis-based device that uses a hybrid albumin-impregnated membrane to get rid of albumin-bound toxins that circulate in abundance in liver failure, called the molecular adsorbent recirculating system (MARS) has been in clinical use for nearly four years now. Results with the use of this device in both acute and acute-on-chronic liver failure have shown consistent improvement in biochemical profile, resolution of encephalopathy, correction in hemodynamics, reduction in intracranial pressure and some improvement in the synthetic function of the liver. In a number of studies, albeit of small sample size, survival advantage has also been observed. The timing of initiation of therapy with MARS, duration of treatment, frequency of sessions and 'maintenance therapy' are still some of the unresolved issues with the use of this device. Large multicentric trials on the use of this technique are expected to throw light on these issues and help optimize the potential of this liver assist device.