A placebo-controlled double blind trial of etanercept for the cancer anorexia/weight loss syndrome: results from N00C1 from the North Central Cancer Treatment Group

BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is a putative mediator of the cancer anorexia/weight loss syndrome. The current study was designed to determine whether etanercept (a dimeric fusion protein consisting of the extracellular ligand-binding portion of the human 75-kilodalton TNF receptor linked to the Fc portion of human immunoglobulin [Ig] G1) could palliate this syndrome. METHODS: A total of 63 evaluable patients were randomly assigned to receive either etanercept at a dose of 25 mg subcutaneously twice weekly versus a comparably administered placebo. All patients had an incurable malignancy, acknowledged loss of weight and/or appetite as a concern, and reported a weight loss of >2.27 kg over 2 months and/or a daily intake of <20 calories/kg body weight. RESULTS: Over time, weight gain was found to be minimal in both treatment arms; no patient gained >or=10% of their baseline weight. Previously validated appetite questionnaires revealed negligible improvements in both treatment arms. The median survival was also comparable (175 days vs 148 days in etanercept-treated and placebo-exposed patients, respectively; P = .82). Finally, preliminary data regarding adverse events demonstrated that patients treated with etanercept had higher rates of neurotoxicity (29% vs 0%) but lower rates of anemia (0% vs 19%) and thrombocytopenia (0% vs 14%). Infection rates were negligible in both groups. Genotyping for TNF-alpha-238 and TNF-alpha-308 polymorphisms revealed no clinical significance for these genotypes, except for a preliminary association between presence of the -238 G/A genotype and relatively less favorable survival. CONCLUSIONS: Etanercept, as prescribed in the current trial, does not appear to palliate the cancer anorexia/weight loss syndrome in patients with advanced disease.     

Managing treatment-induced emesis: a nursing perspective.

Patients with cancer undergoing treatment with chemotherapy or radiation therapy may experience a range of treatment-related side effects. One of the most common and most distressing side effects is treatment-induced emesis. The severity of the symptom is great enough to cause some patients to refuse treatments, delay appointments or discontinue therapy entirely. Experiencing treatment-induced nausea and vomiting can create a spectrum of issues for patients and their families and seriously influence their quality of life. Managing nausea and vomiting induced by cancer therapy is of critical importance. A team approach, inclusive of the patient, can be most effective. Nurses play a pivotal role in assessing patterns of nausea and vomiting and the usefulness of anti-emetic therapy, evaluating and updating treatment/care plans and helping the patient and family to cope with the disease and its treatment.     

Replantation in children

The authors have replanted 162 parts in 120 children over the past 15 years. The youngest patient, undergoing successful replantation, was aged 7 months, 3 weeks. Unlike an adult, any child suffering a traumatic amputation should be considered for a possible replantation. Replantation should consist of minimal bone shortening to preserve epiphyseal plates, with repair of all severed structures. Longitudinal K-wires usually provide adequate fixation. Our survival rate for complete replantation in children under the age of 16 years is 77%. Long-term study showed that continued skeletal growth occurred and the digit attained 81% of normal longitudinal length at maturity. Recovery of sensibility in the replanted digit is nearly as good as for isolated digital nerve repair. Patient and parent satisfaction is high when replantation is successful, with uniform approval of the extensive effort required.     

Amodiaquin accumulation by mouse erythrocytes infected with Plasmodium berghei.

[14C]amodiaquin accumulation by washed erythrocyte preparations was characterized to permit comparisons with chloroquine accumulation. Erythrocytes infected with Plasmodium berghei CS (chloroquine-susceptible) accumulate amodiaquin by a saturable process that has an apparent dissociation constant for amodiaquin of 7.6 X 10(-8) M and is competitively inhibited by chloroquine, quinine and quinacrine, as is the process of chloroquine accumulation. Within experimental error, the K1 of 8 X 10(-7) M estimated for chloroquine is the same regardless of whether the drug being accumulated is [14C]amodiaquin or [14C]chloroquine. Likewise, the K1 for amodiaquin is the same regardless of which drug is being accumulated. In addition, glucose stimulates and hydrogen ion, cold or interruption of glycolysis inhibits amodiaquin as well as chloroquine accumulation. These findings are evidence that a single process serves to accumulate both drugs. In the absence of substrate, erythrocytes infected with P. berghei CR (chloroquine-resistant) accumulate twice as much amodiaquin as chloroquine, and they accumulate more amodiaquin than do erythrocytes infected with P. berghei CS. These differences occur because P. berghei CR infects polychromatophilic erythrocytes possessing a high-affinity, substrate-independent process of accumulation to which amodiaquin has greater access than chloroquine. In the presence of glucose, amodiaquin accumulation by erythrocytes infected with P. berghei CR, when plotted as a function of amodiaquin concentration in the medium, describes a sigmoid curve.     

Understanding the supportive care needs of parents of children with cancer: an approach to local needs assessment.

The objective of this study was to conduct an assessment of supportive care needs from the perspective of parents of children diagnosed with cancer within an urban-rural region in Eastern Ontario, Canada. Guided by a conceptual framework for supportive care, the exploratory, mixed-method study used a standard needs survey and semistructured interviews. Fifteen parents completed (75% response rate) the survey, and 3 parents participated as key informants in the follow-up interview. Parents reported needs in all 6 of the need categories outlined within the Supportive Care Needs Framework. The proportion of parents expressing a need ranged from 23% to 39%. Dealing with the fear of their child's cancer spreading was frequently identified by parents. Emotional and informational needs were the 2 most frequently acknowledged categories of need. With further refinement, the use of the conceptual framework will provide a methodology for planning care based on the individual needs identified by parents of children with cancer.     

Toxic heme in sickle cells: an explanation for death of malaria parasites

In an effort to elucidate a mechanism of genetic resistance to malaria, we asked whether a toxic form of heme is included in the excess of ferriprotoporphyrin IX (FP) which has been reported to accumulate as hemichromes in sickle cells. When FP is bound to certain erythrocytic elements, such as native hemoglobin, it is inaccessible to bind chloroquine with high affinity and is nontoxic. However, when FP is accessible to bind chloroquine with high affinity, it has been demonstrated to be sufficiently free to have membrane toxicity and, under certain conditions, to lyse Plasmodium falciparum parasites. [14C]-chloroquine was used, therefore, as a reporter molecule to evaluate the quantity, accessibility, and potential toxicity of FP released from hemoglobin. Intact erythrocytes from subjects with sickle cell anemia bound approximately 71 mumoles of chloroquine per kg with an apparent Kd of 10(-6) M. Erythrocytes from normal subjects or subjects with sickle trait bound little or no chloroquine with high affinity. Since the oxidant stress introduced by malaria parasites would increase the tendency for denaturation of hemoglobin S with additional release of FP, we suggest that FP toxicity accounts for the death of malaria parasites in sickle cells.     

Respiratory health of elite athletes - preventing airway injury: a critical review

Elite athletes, particularly those engaged in endurance sports and those exposed chronically to airborne pollutants/irritants or allergens, are at increased risk for upper and lower airway dysfunction. Airway epithelial injury may be caused by dehydration and physical stress applied to the airways during severe exercise hyperpnoea and/or by inhalation of noxious agents. This is thought to initiate an inflammatory cascade/repair process that, ultimately, could lead to airway hyperresponsiveness (AHR) and asthma in susceptible athletes. The authors review the evidence relating to prevention or reduction of the risk of AHR/asthma development. Appropriate measures should be implemented when athletes exercise strenuously in an attempt to attenuate the dehydration stress and reduce the exposure to noxious airborne agents. Environmental interventions are the most important. Non-pharmacological strategies can assist, but currently, pharmacological measures have not been demonstrated to be effective. Whether early prevention of airway injury in elite athletes can prevent or reduce progression to AHR/asthma remains to be established.