A phase III, randomized, non-inferiority study comparing the efficacy and safety of biosimilar filgrastim versus originator filgrastim for chemotherapy-induced neutropenia in breast cancer patients

OBJECTIVES: To compare the efficacy and safety of two filgrastim formulations for controlling chemotherapy-induced neutropenia and to evaluate the non-inferiority of the test drug relative to the originator. METHODS: This phase III non-inferiority study had a randomized, multicenter, and open-label design. The patients were randomized at a ratio of 1:1 with a follow-up period of 6 weeks for each patient. In both study arms, filgrastim was administered subcutaneously at a daily dose of 5 mg/kg body weight. The primary endpoint was the rate of grade 4 neutropenia in the first treatment cycle. The secondary endpoints were the duration of grade 4 neutropenia, the generation of anti-filgrastim antibodies, and the rates of adverse events, laboratory abnormalities, febrile neutropenia, and neutropenia of any grade. RESULTS: The primary efficacy analysis demonstrated the non-inferiority of the test drug compared with the originator drug; the upper limit of the 90% confidence interval (CI) for the rate of neutropenia between the two groups (12.61%) was lower than the established margin of non-inferiority. The two treatments were similar with respect to the secondary endpoints and safety. CONCLUSION: The efficacy and safety profile of the test drug were similar to those of the originator product based on the rate of grade 4 neutropenia in the first treatment cycle. This study supports Anvisa’s approval of the first biosimilar drug manufactured by the Brazilian industry (Fiprima¯).

Stroke in children.

Stroke is defined as the sudden occlusion or rupture of cerebral arteries or veins resulting in focal cerebral damage and neurological deficits. Forms of stroke resulting from vascular occlusion are arterial ischemic stroke (AIS) and sinovenous thrombosis (SVT) and those resulting from vascular rupture are called hemorrhagic stroke. Stroke in children is relatively rare and frequently results in a lack of recognition and delay in diagnosis. The etiologies of stroke in children are legion and multiple risk factors coexist unlike unifactorial etiology in adults. Heart disease whether congenital or acquired, malformations, metabolic and hematological disorders and vasospastic conditions like migraine are seen more often in childhood strokes. The purpose of diagnostic evaluation includes confirmation of the presence of a cerebrovascular lesion, exclusion of other types of neurological dysfunction and identification of etiology of the stroke. The treatment of stroke in children has been primarily directed toward stabilizing systemic factors and management of the underlying causes. Various antithrombotic and non antithrombotic therapies are discussed. The use of anticoagulant therapy appears to be increasing in pediatric AIS. Mortality after stroke in children ranges from 20% to 30% depending on the location and the underlying cause. Residual neurological dysfunction is present in more than 50% of survivors.

Immediate treatment of frostbite using rapid rewarming in tea decoction followed by combined therapy of pentoxifylline, aspirin & vitamin C.

BACKGROUND & OBJECTIVES: Frostbite, the severest form of cold injury is a serious medical problem for our Armed Forces operating in the snow bound areas at high altitude. Effects of treatment by rapid rewarming in tea decoction followed by combined therapy of pentoxifylline, aspirin and vitamin C were evaluated in amelioration of tissue damage due to experimentally induced frostbite in rats. METHODS: Experiments were conducted in 2 groups (25 each) of albino rats (control i.e., untreated and experimental i.e., treated). Frostbite was produced experimentally in all the animals by exposing one of the hind limbs at -12 +/- 1 degree C with wind flow 25-30 lit/min for 30 min in a freezing-machine, with simultaneous recordings of rectal and ambient temperatures. The degree of tissue damage was assessed after 10 days. Following cold exposure, neither external thawing nor any medication was given to the animals of the control group; while the exposed limb of the experimental animals was rewarmed in tea decoction maintained at 37-39 degrees C for 30 min immediately after cold exposure, with simultaneous oral ingestion of warm tea decoction. These animals were also given pentoxifylline (40 mg/kg), aspirin (5 mg/kg) and vitamin C (50 mg/kg) twice daily orally for the next 7 days. RESULTS: In the control group, 68 per cent animals suffered from severe (56%) to very severe (12%) frostbite, while the remaining 32 per cent had moderate frostbite. No animals of this group could escape injury or suffered anything less than moderate frostbite; whereas 52 per cent of experimental animals escaped injury (no frostbite) and 32 and 16 per cent suffered only with primary and moderate degree of injury, respectively. None from this group suffered from severe or very severe frostbite. INTERPRETATION & CONCLUSION: It is evident from the study that this combined therapy resulted in significant improvement in the degree of tissue preservation and proved to be highly beneficial as an immediate treatment of frostbite in rats. The combined pharmacological properties of these drugs might have altered the haemorrheologic status of blood and produced curative beneficial effect in improving tissue survival. Clinical studies are required for confirmation of these beneficial effects in humans, which has already been taken up.